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It is often neglected that the ability of birds to extract navigational information from the earth's magnetic field can be shaped by learning and memory, which would necessarily recruit brain regions of the telencephalon that support cognitive processes. In the current study, we exploited a validated, conditioning experimental paradigm to explore the possible role of the homing pigeon hippocampal formation (HF) and anterior forebrain Wulst in the detection of variation in both magnetic field intensity and inclination. Whereas HF lesions resulted in a complete loss of intensity discrimination while sparing inclination discrimination, Wulst lesions had the opposite effect, resulting in a complete loss of inclination discrimination while sparing intensity discrimination. It is not surprising that Wulst lesions should disrupt inclination discrimination because in migratory songbirds, regions of the Wulst are known to support the geomagnetic compass, which relies on inclination. More challenging is explaining why HF should be sensitive to variation in magnetic intensity. We suggest that the observed HF sensitivity to intensity may reflect incorporation of geomagnetic irregularities (anomalies) as pigeons learn a map-like representation of familiar landmarks and landscape features. The parallel processing of magnetic intensity and inclination in the homing pigeon forebrain sets the foundation for future studies designed to better understand how cognitive processing can influence geomagnetically guided navigational behavior in birds. [ABSTRACT FROM AUTHOR]

Background: Majority of neuroblastoma patients develop metastatic disease at diagnosis and their prognosis is poor with current therapeutic approach. Major challenges are how to tackle the mechanisms responsible for tumorigenesis and metastasis. Human mesenchymal stem cells (hMSCs) may be actively involved in the constitution of cancer microenvironment.Methods: An orthotopic neuroblastoma murine model was utilized to mimic the clinical scenario. Human neuroblastoma cell line SK-N-LP was transfected with luciferase gene, which were inoculated with/without hMSCs into the adrenal area of SCID-beige mice. The growth and metastasis of neuroblastoma was observed by using Xenogen IVIS 100 in vivo imaging and evaluating gross tumors ex vivo. The homing of hMSCs towards tumor was analyzed by tracing fluorescence signal tagged on hMSCs using CRI Maestro™ imaging system.Results: hMSCs mixed with neuroblastoma cells significantly accelerated tumor growth and apparently enhanced metastasis of neuroblastoma in vivo. hMSCs could be recruited by primary tumor and also become part of the tumor microenvironment in the metastatic lesion. The metastatic potential was consistently reduced in lung and tumor when hMSCs were pre-treated with stromal cell derived factor-1 (SDF-1) blocker, AMD3100, suggesting that the SDF-1/CXCR4 axis was one of the prime movers in the metastatic process.Conclusions: hMSCs accelerated and facilitated tumor formation, growth and metastasis. Furthermore, the homing propensity of hMSCs towards both primary tumor and metastatic loci can also provide new therapeutic insights in utilizing bio-engineered hMSCs as vehicles for targeted anti-cancer therapy. [ABSTRACT FROM AUTHOR]

Neurological disorders are becoming a growing burden as society ages, and there is a compelling need to address this spiraling problem. Stem cell‐based regenerative medicine is becoming an increasingly attractive approach to designing therapies for such disorders. The unique characteristics of mesenchymal stem cells (MSCs) make them among the most sought after cell sources. Researchers have extensively studied the modulatory properties of MSCs and their engineering, labeling, and delivery methods to the brain. The first part of this review provides an overview of studies on the application of MSCs to various neurological diseases, including stroke, traumatic brain injury, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's disease, and other less frequently studied clinical entities. In the second part, stem cell delivery to the brain is focused. This fundamental but still understudied problem needs to be overcome to apply stem cells to brain diseases successfully. Here the value of cell engineering is also emphasized to facilitate MSC diapedesis, migration, and homing to brain areas affected by the disease to implement precision medicine paradigms into stem cell‐based therapies. [ABSTRACT FROM AUTHOR]

Background: The bone marrow mesenchymal stem cell (BMSCs)-derived extracellular vesicles (EVs) open up a new avenue for ulcerative colitis (UC) treatment recently, but they are not selectively enriched in targeted tissues. EphB2, a cell-to-cell signaling receptor, is identified as a regulator for inflammatory response, immune homeostasis and cell migration. In this study, we investigated the therapeutic potential and underlying mechanism for EphB2 over-expressing BMSCs derived EVs (EphB2-EVs) in the treatment of UC. Methods: BMSCs and EVs were obtained and characterized by a series of experiments. Lentivirus vector encoding EphB2 was transfected into BMSCs and verified by qRT-PCR. We analyzed the EphB2-EVs ability of colonic targeting in a DSS-induced colitis model by using confocal microscope and WB. The protective effect of EphB2-EVs in vivo was systematically evaluated by using a series of function experiments. Results: We successfully constructed EphB2-overexpressing BMSCs derived EVs (EphB2-EVs). Overexpression of EphB2 significantly enhanced the homing of EVs to the damaged colon. In addition, EphB2-EVs were effective to attenuate inflammation in intestinal mucosa and restore the damaged colon tissue by inhibiting the release of proinflammatory cytokines and upregulating the anti-inflammatory mediators. EphB2-EVs effectively reduced the oxidative stress and repaired the intestinal mucosal barrier in the UC rats. Moreover, EphB2-EVs demonstrated a robust immunomodulatory effect to restore immune homeostasis via modulating Th17/Treg balance and restraining STAT3 activation. Conclusions: Our results suggest that EphB2-EVs have high colonic targeting ability and could mitigate DSS-induced colitis via maintaining colonic immune homeostasis. These findings provide an effective therapeutic strategy for UC treatment in clinic. [ABSTRACT FROM AUTHOR]

Cord blood transplantation (CBT) has been widely used in the treatment of hematologic malignancies and non-malignant hematologic diseases both in children and adults. Compared with other sources of hematopoietic stem/progenitor cell (HSPC) transplantation, CBT has a higher rate of engraftment failure and delayed hematopoietic system and immune system recovery, thereby increasing the mortality caused by infection and other transplant-related complications. Therefore, how to promote the engraftment of cord blood HSPC has been a hot spot in CBT for many years. The article reviews the latest advances in the strategies to improve the engraftment of HSPC of cord blood. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) represent a major population controlling T cell immune responses. However, little is known about their molecular requirements for homing and T cell interaction to mediate suppression. Here, we investigated the functional role of the homing and collagen IV receptor VLA-1 (α1β1-integrin) on in vitro GM-CSF generated murine MDSCs from wild-type (WT) and CD49a/α1-integrin (Itga1−/−) gene-deficient mice. Here, we found that effector (Teff) but not naive (Tn) CD4+ T cells express VLA-1 and monocytes further up-regulated their expression after culture in GM-CSF when they differentiated into the monocytic subset of resting MDSCs (R-MDSCs). Subsequent activation of R-MDSCs by LPS+IFN-γ (A-MDSCs) showed increased in vitro suppressor potential, which was independent of VLA-1. Surprisingly, VLA-1 deficiency did not influence A-MDSC motility or migration on collagen IV in vitro. However, interaction times of Itga1−/− A-MDSCs with Teff were shorter than with WT A-MDSCs on collagen IV but not on fibronectin substrate in vitro. After injection, A-MDSCs homed to the splenic red pulp where they co-localized with Teff and showed immediate suppression already after 6 h as shown by inhibition of T cell proliferation and induction of apoptosis. Injection of A-MDSCs from Itga1−/− mice showed equivalent homing into the spleen but a reduced suppressive effect. Interaction studies of A-MDSCs with Teff in the subcapsular red pulp with intravital two-photon microscopy revealed also here that MDSC motility and migration parameters were not altered by VLA-1 deficiency, but the interaction times with Teff were reduced. Together, our data point to a new role of VLA-1 adhesion to collagen IV as a prerequisite for extended contact times with Teff required for suppression.

The WAC Bennett Dam was completed in 1968 and impounded the Upper Peace River to form the Williston Reservoir in north central British Columbia. In 1990, an enhancement project was initiated to stock Columbia River Kokanee (non-anadromous Sockeye Salmon; Oncorhynchus nerka) from southeastern British Columbia into tributary streams that drained into regions of the reservoir that were accessible by anglers. The current distribution of spawning Columbia-origin Kokanee in the Williston Reservoir watershed, however, does not reflect the locations where these fish were initially stocked and suggests extensive straying. Whether or not Kokanee will develop fidelity to specific spawning locations is not known, but it is important information to effectively manage these introduced fish. We used otolith microchemistry to estimate fidelity to natal streams by Columbia-origin Kokanee in the Williston Reservoir. Otolith elemental signatures for the region of the otolith that formed during the larval period and characterized the natal redd environment showed considerable variation among samples. Natal signatures tended to cluster for each river but not for all spawners, suggesting elemental signatures from other rivers. Homing to one of the four natal streams we examined was classified to be 73% based on linear discriminant analysis, although variation in the elemental signatures within each group suggests that homing by Kokanee to specific natal streams may be as low as 55%. Based on similarity of water elemental signatures for tributaries within large rivers, however, the proportion of fish that returned to their general region was likely higher and estimated to be approximately 83%. The result of regional homing could be reproductive isolation and adaptation to local conditions. It is unclear, however, if the current estimated level of straying will limit genetic differentiation and prevent local adaptation.

Densities of abalone in southern California have been dramatically reduced by overfishing and disease, leading to the collapse of some populations, and low fertilization rates may be hindering population recovery. This is a pattern typical of abalone species globally. However, movement may produce clustered distributions that promote fertilization success in broadcast spawners, such as abalone, even at low regional densities. We translocated wild, adult pink abalone Haliotis corrugata to an existing pink abalone patch to create a high-density aggregation, and then used acoustic telemetry to characterize abalone movement and monitor aggregation maintenance for a period of 14 mo in the Point Loma kelp forest near San Diego, California. Abalone showed a minimal flight response to handling that did not differ between the resident or translocated groups. Most individuals exhibited small home ranges (median area 183 m2) and homing behavior consisting of regular back-and-forth movement to a single point. Nomadic movement was also observed in several individuals. Though site fidelity may help maintain aggregations, abalone density decreased, and nearest neighbor distances increased at our site to nearinitial levels after 18 mo via a combination of mortality, large movements of a few individuals, and small, incremental movements of most individuals. No coordinated movements that would suggest spawning behavior were observed. Translocation of wild abalone to produce aggregations may not result in high rates of fertilization success that promote population recovery. However, the homing behavior observed may provide more opportunities for mating than expectations based on static measures of density and aggregation state. © Inter-Research 2013.

Isolated myeloid sarcoma (MS) is a rare malignancy in which myeloid blast forms tumors at various locations while the bone marrow (BM) remains cytomorphologically free from disease. We analyzed isolated MS from four patients and their BMs at initial diagnosis and follow-up, using a custom next-generation sequencing (NGS) panel. We observed possible clonal evolution and a clonal hematopoiesis of indeterminate potential (CHIP)-like finding in the BM of one of three cases with detectable mutations. Clinical presentation of one patient suggested extramedullary confined homing of blasts to distal sites in the relapse situation still sparing the BM. In summary, our findings shall motivate future work regarding signals of extramedullary blast trafficking and clonal evolution in MS. [ABSTRACT FROM AUTHOR]

Recently, application of stem cell therapy in regenerative medicine has become an active field of study. Mesenchymal stem cells (MSCs) are known to have a strong ability for homing. MSCs labeled with superparamagnetic iron oxide nanoparticles (SPIONs) exhibit enhanced homing due to magnetic attraction. We have designed a SPION that has a cluster core of iron oxide-based nanoparticles coated with PLGA-Cy5.5. We optimized the nanoparticles for internalization to enable the transport of PCS nanoparticles through endocytosis into MSCs. The migration of magnetized MSCs with SPION by static magnets was seen in vitro. The auditory hair cells do not regenerate once damaged, ototoxic mouse model was generated by administration of kanamycin and furosemide. SPION labeled MSC's were administered through different injection routes in the ototoxic animal model. As result, the intratympanic administration group with magnet had the highest number of cells in the brain followed by the liver, cochlea, and kidney as compared to those in the control groups. The synthesized PCS (poly clustered superparamagnetic iron oxide) nanoparticles, together with MSCs, by magnetic attraction, could synergistically enhance stem cell delivery. The poly clustered superparamagnetic iron oxide nanoparticle labeled in the mesenchymal stem cells have increased the efficacy of homing of the MSC's to the target area by synergetic effect of magnetic attraction and chemotaxis (SDF-1/CXCR4 axis). This technique allows delivery of the stem cells to the areas with limited vasculatures. The nanoparticle in the biomedicine allows drug delivery, thus, the combination of nanomedicince together with the regenerative medicine will provide highly effective therapy. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) represent a major population controlling T cell immune responses. However, little is known about their molecular requirements for homing and T cell interaction to mediate suppression. Here, we investigated the functional role of the homing and collagen IV receptor VLA-1 (α1β1-integrin) on in vitro GM-CSF generated murine MDSCs from wild-type (WT) and CD49a/α1-integrin (Itga1 −/−) gene-deficient mice. Here, we found that effector (Teff) but not naive (Tn) CD4+ T cells express VLA-1 and monocytes further up-regulated their expression after culture in GM-CSF when they differentiated into the monocytic subset of resting MDSCs (R-MDSCs). Subsequent activation of R-MDSCs by LPS+IFN-γ (A-MDSCs) showed increased in vitro suppressor potential, which was independent of VLA-1. Surprisingly, VLA-1 deficiency did not influence A-MDSC motility or migration on collagen IV in vitro. However, interaction times of Itga1 −/− A-MDSCs with Teff were shorter than with WT A-MDSCs on collagen IV but not on fibronectin substrate in vitro. After injection, A-MDSCs homed to the splenic red pulp where they co-localized with Teff and showed immediate suppression already after 6 h as shown by inhibition of T cell proliferation and induction of apoptosis. Injection of A-MDSCs from Itga 1−/− mice showed equivalent homing into the spleen but a reduced suppressive effect. Interaction studies of A-MDSCs with Teff in the subcapsular red pulp with intravital two-photon microscopy revealed also here that MDSC motility and migration parameters were not altered by VLA-1 deficiency, but the interaction times with Teff were reduced. Together, our data point to a new role of VLA-1 adhesion to collagen IV as a prerequisite for extended contact times with Teff required for suppression. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effect of erythropoietin (EPO) on the proliferation and migration of bone marrow mesenchymal stem cell (BMSC) in rats. Methods The 5th generation BMSCs were divided into the control (without EPO) and 10, 100, 500, 1 000 IU/mL EPO groups. After 24 h and 48 h of culture, the proliferation rate, migration ability and the expression levels of CXCR4 of BMSCs were detected in each group. The 5th generation BMSCs were further divided into BMSC and EPO-BMSC groups. After 48 h of culture, the effect of EPO upon surface markers, directional differentiation and cytoskeleton morphology of BMSCs were evaluated in both groups. Results After the co-culture of EPO and BMSCs for 48 h, the proliferation rate and migration ability of BMSCs were significantly enhanced, and the expression level of CXCR4 protein was significantly up-regulated in the 100 IU/mL and 500 IU/mL EPO groups compared with those in the control group (all P<0.05). However, EPO exerted no effect upon the expression levels of surface markers and directional differentiation ability of BMSCs in the EPO-BMSC group. In the EPO-BMSC group, the fibrous skeleton of most BMSCs was arranged along the long axis in parallel. Conclusions EPO can improve the proliferation rate, migration ability and tissue repair capability of BMSCs, probably by promoting the directional homing of BMSCs to injured organs and tissues via up-regulating the expression level of CXCR4. [ABSTRACT FROM AUTHOR]

Background: Dystrophinopathy, a common neuromuscular disorder caused by the absence of dystrophin, currently lacks effective treatments. Systemic transplantation of adipose-derived stem cells (ADSCs) is a promising treatment approach, but its low efficacy remains a challenge. Chemokine system-mediated stem cell homing plays a critical role in systemic transplantation. Here, we investigated whether overexpression of a specific chemokine receptor could improve muscle homing and therapeutic effects of ADSC systemic transplantation in dystrophic mice. Methods: We analysed multiple microarray datasets from the Gene Expression Omnibus to identify a candidate chemokine receptor and then evaluated the protein expression of target ligands in different tissues and organs of dystrophic mice. The candidate chemokine receptor was overexpressed using the lentiviral system in mouse ADSCs, which were used for systemic transplantation into the dystrophic mice, followed by evaluation of motor function, stem cell muscle homing, dystrophin expression, and muscle pathology. Results: Chemokine-profile analysis identified C–C chemokine receptor (CCR)2 as the potential target for improving ADSC homing. We found that the levels of its ligands C–C chemokine ligand (CCL)2 and CCL7 were higher in muscles than in other tissues and organs of dystrophic mice. Additionally, CCR2 overexpression improved ADSC migration ability and maintained their multilineage-differentiation potentials. Compared with control ADSCs, transplantation of those overexpressing CCR2 displayed better muscle homing and further improved motor function, dystrophin expression, and muscle pathology in dystrophic mice. Conclusions: These results demonstrated that CCR2 improved ADSC muscle homing and therapeutic effects following systemic transplantation in dystrophic mice. [ABSTRACT FROM AUTHOR]

Insects play important roles as predators, prey, pollinators, recyclers, hosts, parasitoids, and sources of economically important products. They can also destroy crops; wound animals; and serve as vectors for plant, animal, and human diseases. Gene drive—a process by which genes, gene complexes, or chromosomes encoding specific traits are made to spread through wild populations, even if these traits result in a fitness cost to carriers—provides new opportunities for altering populations to benefit humanity and the environment in ways that are species specific and sustainable. Gene drive can be used to alter the genetic composition of an existing population, referred to as population modification or replacement, or to bring about population suppression or elimination. We describe technologies under consideration, progress that has been made, and remaining technological hurdles, particularly with respect to evolutionary stability and our ability to control the spread and ultimate fate of genes introduced into populations. [ABSTRACT FROM AUTHOR]

C-X-C chemokine receptor type 4 (CXCR4), initially recognized as a co-receptor for HIV, contributes to several disorders, including the WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome. CXCR4 binds to its ligand SDF-1 to make an axis involved in the homing property of stem cells. This study aimed to employ WHIM syndrome pathogenesis as an inspirational approach to reinforce cell therapies. Wild type and WHIM-type variants of the CXCR4 gene were chemically synthesized and cloned in the pCDH-513B-1 lentiviral vector. Molecular cloning of the synthetic genes was confirmed by DNA sequencing, and expression of both types of CXCR4 at the protein level was confirmed by western blotting in HEK293T cells. Human adipose-derived mesenchymal stem cells (Ad-MSCs) were isolated, characterized, and subjected to lentiviral transduction with Wild type and WHIM-type variants of CXCR4. The presence of copGFP-positive MSCs confirmed the high efficiency of transduction. The migration ability of both groups of transduced cells was then assessed by transwell migration assay in the presence or absence of a CXCR4-blocking agent. Our qRT-PCR results showed overexpression of CXCR4 at mRNA level in both groups of transduced MSCs, and expression of WHIM-type CXCR4 was significantly higher than Wild type CXCR4 (P <0.05). Our results indicated that the migration of genetically modified MSCs expressing WHIM-type CXCR4 had significantly enhanced towards SDF1 in comparison with Wild type CXCR4 (P <0.05), while it was reduced after treatment with CXCR4 antagonist. These data suggest that overexpression of WHIM-type CXCR4 could lead to enhanced and sustained expression of CXCR4 on human MSCs, which would increase their homing capability; hence it might be an appropriate strategy to improve the efficiency of cell-based therapies. [ABSTRACT FROM AUTHOR]

The frequency of reproduction and homing success are crucial in determining the lifetime reproductive fitness of iteroparous salmonids. We examined consecutive spawning and homing by Sakhalin taimen (Parahucho perryi), one of the least-studied iteroparous salmonids. The average consecutive return rate was 69.5%, the highest ever reported for an iteroparous salmonid. The consecutive return rates were highest for large spawners, females, and individuals with active inter-tributary movements in the preceding year. We estimated tributary-scale repeat homing rates to be 50–87%, which was significantly higher than expected by chance alone. The repeat homing rates were higher for spawners that entered tributaries with more abundant spawners in the preceding year, which is consistent with the pheromone hypothesis because the abundance of spawners in a tributary is expected to correlate to the concentration of chemical homing cues emanating from offspring in the following year. These extremely high consecutive return and homing rates likely facilitated local adaptation over evolutionary time scales and have contributed to population stability in this river system. These same traits, however, may impede species recovery following habitat restoration efforts within the species historic range (e.g. dam barrier removal or improved passage) due to their limited rate of dispersal. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) have a critical role in maintaining self‐tolerance and immune homeostasis. There is much interest in using Tregs as a cell therapy to re‐establish tolerance in conditions such as inflammatory bowel disease and type 1 diabetes, with many ongoing clinical studies testing the safety and efficacy of this approach. Manufacturing of Tregs for therapy typically involves ex vivo expansion to obtain sufficient cell numbers for infusion and comes with the risk of altering the activity of key biological processes. However, this process also offers an opportunity to tailor Treg function to maximize in vivo activity. In this review, we focus on the roles of antigen‐presenting cells (APCs) in the generation and function of Tregs in humans. In addition to stimulating the development of Tregs, APCs activate Tregs and provide signals that induce specialized functional and homing marker expression. Cross talk between Tregs and APCs is a critical, often under‐appreciated, aspect of Treg biology, with APCs mediating the key properties of infectious tolerance and bystander suppression. Understanding the biology of human Treg‐APC interactions will reveal new ways to optimize Treg‐based therapeutic approaches. [ABSTRACT FROM AUTHOR]

CD44 is a ubiquitous leukocyte adhesion molecule involved in cell-cell interaction, cell adhesion, migration, homing and differentiation. CD44 can mediate the interaction between leukemic stem cells and the surrounding extracellular matrix, thereby inducing a cascade of signaling pathways to regulate their various behaviors. In this review, we focus on the impact of CD44s/CD44v as biomarkers in leukemia development and discuss the current research and prospects for CD44-related interventions in clinical application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Tan, Li, Han, Zhang and Lin.)

Tissue infiltration by circulating leukocytes occurs via adhesive interactions with the local vasculature, but how the adhesive quality of circulating cells guides the homing of specific phenotypes to different vascular microenvironments remains undefined. We developed an optofluidic system enabling fluorescent labeling of photoactivatable cells based on their adhesive rolling velocity in an inflamed vasculature-mimicking microfluidic device under physiological fluid flow. In so doing, single-cell level multidimensional profiling of cellular characteristics could be characterized and related to the associated adhesive phenotype. When applied to CD8 + T cells, ligand/receptor expression profiles and subtypes associated with adhesion were revealed, providing insight into inflamed tissue infiltration capabilities of specific CD8 + T lymphocyte subsets and how local vascular microenvironmental features may regulate the quality of cellular infiltration. This methodology facilitates rapid screening of cell populations for enhanced homing capabilities under defined biochemical and biophysical microenvironments, relevant to leukocyte homing modulation in multiple pathologies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Suppressive function of regulatory T cells (Treg) is dependent on signaling of their antigen receptors triggered by cognate self, dietary, or microbial peptides presented on MHC II. However, it remains largely unknown whether distinct or shared repertoires of Treg TCRs are mobilized in response to different challenges in the same tissue or the same challenge in different tissues. Here we use a fixed TCRβ chain FoxP3-GFP mouse model to analyze conventional (eCD4) and regulatory (eTreg) effector TCRα repertoires in response to six distinct antigenic challenges to the lung and skin. This model shows highly 'digital' repertoire behavior with easy-to-track challenge-specific TCRα CDR3 clusters. For both eCD4 and eTreg subsets, we observe challenge-specific clonal expansions yielding homologous TCRα clusters within and across animals and exposure sites, which are also reflected in the draining lymph nodes but not systemically. Some CDR3 clusters are shared across cancer challenges, suggesting a response to common tumor-associated antigens. For most challenges, eCD4 and eTreg clonal response does not overlap. Such overlap is exclusively observed at the sites of certain tumor challenges, and not systematically, suggesting transient and local tumor-induced eCD4=>eTreg plasticity. This transition includes a dominant tumor-responding eCD4 CDR3 motif, as well as characteristic iNKT TCRα CDR3. In addition, we examine the homeostatic tissue residency of clonal eTreg populations by excluding the site of challenge from our analysis. We demonstrate that distinct CDR3 motifs are characteristic of eTreg cells residing in particular lymphatic tissues, regardless of the challenge. This observation reveals the tissue-resident, antigen-specific clonal Treg populations., Competing Interests: TN, BM, EP, SL, DB, OB, MS, DC No competing interests declared, (© 2023, Nakonechnaya, Moltedo, Putintseva et al.)

A transplanted stem cell's engagement with a pathologic niche is the first step in its restoring homeostasis to that site. Inflammatory chemokines are constitutively produced in such a niche; their binding to receptors on the stem cell helps direct that cell's "pathotropism." Neural stem cells (NSCs), which express CXCR4, migrate to sites of CNS injury or degeneration in part because astrocytes and vasculature produce the inflammatory chemokine CXCL12. Binding of CXCL12 to CXCR4 (a G protein-coupled receptor, GPCR) triggers repair processes within the NSC. Although a tool directing NSCs to where needed has been long-sought, one would not inject this chemokine in vivo because undesirable inflammation also follows CXCL12-CXCR4 coupling. Alternatively, we chemically "mutated" CXCL12, creating a CXCR4 agonist that contained a strong pure binding motif linked to a signaling motif devoid of sequences responsible for synthetic functions. This synthetic dual-moity CXCR4 agonist not only elicited more extensive and persistent human NSC migration and distribution than did native CXCL 12, but induced no host inflammation (or other adverse effects); rather, there was predominantly reparative gene expression. When coadministered with transplanted human induced pluripotent stem cell-derived hNSCs in a mouse model of a prototypical neurodegenerative disease, the agonist enhanced migration, dissemination, and integration of donor-derived cells into the diseased cerebral cortex (including as electrophysiologically-active cortical neurons) where their secreted cross-corrective enzyme mediated a therapeutic impact unachieved by cells alone. Such a "designer" cytokine receptor-agonist peptide illustrates that treatments can be controlled and optimized by exploiting fundamental stem cell properties (e.g., "inflammo-attraction"). [ABSTRACT FROM AUTHOR]

Coho Salmon Oncorhynchus kisutch show fidelity to natal spawning watersheds. Fine‐scale homing, however, within rivers is not well understood. Interior Fraser Coho (IFC) salmon eggs were incubated at known spawning locations in the Coldwater River, two main stem sites and one‐off channel pond site, providing otolith reference data for comparison to otolith signatures for returning adults using laser ablation inductively coupled plasma mass spectrometry. Elemental ratios for Ba:Ca and Sr:Ca in otoliths of juvenile O. kisutch differed significantly among the spawning locations examined. Juvenile otolith data were used to conduct a linear discriminant analysis to assess fine‐scale homing in adults. Juvenile data were all assigned to the location where they had been incubated, producing a robust data set used to compare adult otoliths and define natal locations based on elemental signatures in otoliths of adult spawners. Homing and straying were apparent at the reach level; 57.1% of adults returned to their natal spawning locations, while 42.9% strayed to other spawning sites within the Coldwater River. Straying to novel incubation sites at the reach scale demonstrated plasticity in homing within a watershed. [ABSTRACT FROM AUTHOR]

In altricial birds, to address which cues are used by parents to recognize their offspring, and when they switch between cues during reproduction, it has not been well determined. In this study, we address this question in a Tibetan population of the azure-winged magpie Cyanopica cyanus , by examining the dependence of parents on a nest's spatial position in offspring recognition. During the egg and nestling phases, azure-winged magpie nests were translocated to new positions across various distances from their original site, and parental responses to the translocated nests were investigated. Our findings show that a nest's spatial position is not connected with the survival of its young, but might be used as a cue in parental offspring recognition. When nests are translocated to a new position within a certain distance, parents could recognize their nests and returned to resume their parenting behaviors. Parental dependence on the nest's spatial position in offspring recognition is higher during the egg phase than during the nestling phase, and it decreases with the growth of nestlings. After nestlings reach a certain age, the nest' s spatial position was no longer used by parents as the single cue for offspring recognition. These findings suggest that azure-winged magpies switch their cues in offspring recognition during the different stages of reproduction. After parent–offspring communication has been established, the offspring's phenotypic traits may become a more reliable cue than the nest's spatial position in offspring recognition. [ABSTRACT FROM AUTHOR]

Background: Limited knowledge of stem cell therapies` mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested whether adhesion receptors and chemokine receptors on stem cells can be functionally modulated, and consequently if such modulation may substantially affect therapeutically relevant stem cell interactions with the host endothelium. Methods: We investigated the effects of cationic molecule polyethylenimine (PEI) treatment with or without nanoparticles on the functions of adhesion receptors and chemokine receptors of human bone marrow-derived Mesenchymal Stem Cells (MSC). Analyses included MSC functions in vitro, as well as homing and therapeutic efficacy in rodent models of central nervous system´s pathologies in vivo. Findings: PEI treatment did not affect viability, immunomodulation or differentiation potential of MSC, but increased the CCR4 expression and functionally blocked their adhesion receptors, thus decreasing their adhesion capacity in vitro. Intravenously applied in a rat model of brain injury, the homing rate of PEI-MSC in the brain was highly increased with decreased numbers of adherent PEI-MSC in the lung vasculature. Moreover, in comparison to untreated MSC, PEI-MSC featured increased tumour directed migration in a mouse glioblastoma model, and superior therapeutic efficacy in a murine model of stroke. Interpretation: Balanced stem cell adhesion and migration in different parts of the vasculature and tissues together with the local microenvironment impacts their therapeutic efficacy. Funding: Robert Bosch Stiftung, IZEPHA grant, EU grant 7 FP Health

Acute myeloid leukemia (AML) is a heterogeneous, complex, and deadly disease, whose treatment has hardly evolved for decades and grounds on the use of intensive chemotherapy regimens. Chemotherapy helps reduce AML bulk, but promotes relapse in the long-run by selection of chemoresistant leukemia stem cells (LSC). These may diversify and result in progression to more aggressive forms of AML. In vivo models suggest that the bone marrow stem cell niche helps LSC stay dormant and protected from chemotherapy. Here, we summarize relevant changes in stem cell niche homing and adhesion of AML LSC vs. healthy hematopoietic stem cells, and provide an overview of clinical trials aiming at targeting these processes for AML treatment and future directions within this field. Promising results with various non-mutation-targeted novel therapies directed to LSC eradication via interference with their anchoring to the stem cell niche have encouraged on-going or future advanced phase III clinical trials. In the coming years, we may see a shift in the focus of AML treatment to LSC-directed therapies if the prospect of improved cure rates holds true. In the future, AML treatment should lean toward personalized therapies using combinations of these compounds plus mutation-targeted agents and/or targeted delivery of chemotherapy, aiming at LSC eradication with reduced side effects.

Despite anecdotal reports of the astonishing homing abilities in dogs, their homing strategies are not fully understood. We equipped 27 hunting dogs with GPS collars and action cams, let them freely roam in forested areas, and analyzed components of homing in over 600 trials. When returning to the owner (homewards), dogs either followed their outbound track (‘tracking’) or used a novel route (‘scouting’). The inbound track during scouting started mostly with a short (about 20 m) run along the north-south geomagnetic axis, irrespective of the actual direction homewards. Performing such a ‘compass run’ significantly increased homing efficiency. We propose that this run is instrumental for bringing the mental map into register with the magnetic compass and to establish the heading of the animal.

With high clinical interest to be applied in regenerative medicine, Mesenchymal Stem/Stromal Cells have been widely studied due to their multipotency, wide distribution, and relative ease of isolation and expansion in vitro. Their remarkable biological characteristics and high immunomodulatory influence have opened doors to the application of MSCs in many clinical settings. The therapeutic influence of these cells and the interaction with the immune system seems to occur both directly and through a paracrine route, with the production and secretion of soluble factors and extracellular vesicles. The complex mechanisms through which this influence takes place is not fully understood, but several functional manipulation techniques, such as cell engineering, priming, and preconditioning, have been developed. In this review, the knowledge about the immunoregulatory and immunomodulatory capacity of MSCs and their secretion products is revisited, with a special focus on the phenomena of migration and homing, direct cell action and paracrine activity. The techniques for homing improvement, cell modulation and conditioning prior to the application of paracrine factors were also explored. Finally, multiple assays where different approaches were applied with varying success were used as examples to justify their exploration.

Abstract Background Bone marrow is an important source of stem cells, which can promote bone fracture healing. Methods We investigated the optimal time to inject bone marrow mesenchymal stem cells (BMSCs) in a C57 murine unilateral, transverse, femur fracture model. BMSCs transfected with red fluorescent protein (RFP-BMSCs) were injected via the tail vein on day 1, 7, or 14 post-fracture. AMD3100 (inhibitor of stromal cell-derived factor 1 [SDF-1]) was also injected before RFP-BMSCs in one group for comparison; a control group received saline injections. RFP-BMSC migration and fracture healing were evaluated by in vivo fluorescence assay. Micro-CT was performed and mechanical testing and histological analysis. Chemokine levels were evaluated by quantitative real-time PCR and western blotting. Results Following injection on day 7 post-fracture, RFP-BMSCs more frequently homed to the fracture site and remained for a longer duration. Bone volume and bone mineral density were increased when BMSCs were injected on day 7 post-fracture (P

Abstract The development of mesenchymal stem cells (MSCs) as cell‐based drug delivery vectors for numerous clinical indications, including cancer, has significant promise. However, a considerable challenge for effective translation of these approaches is the limited tumor tropism and broad biodistribution observed using conventional MSCs, which raises concerns for toxicity to nontarget peripheral tissues (i.e., the bad). Consequently, there are a variety of synthetic engineering platforms in active development to improve tumor‐selective targeting via increased homing efficiency and/or specificity of drug activation, some of which are already being evaluated clinically (i.e., the good). Unfortunately, the lack of robust quantification and widespread adoption of standardized methodologies with high sensitivity and resolution has made accurate comparisons across studies difficult, which has significantly impeded progress (i.e., the ugly). Herein, we provide a concise review of active and passive MSC homing mechanisms and biodistribution postinfusion; in addition to in vivo cell tracking methodologies and strategies to enhance tumor targeting with a focus on MSC‐based drug delivery strategies for cancer therapy. Stem Cells Translational Medicine 2018;1–13

The CXCL12–CXCR4 axis plays a key role in the retention of stem cells and progenitors in dedicated bone marrow niches. It is well-known that CXCR4 responsiveness in B lymphocytes decreases dramatically during the final stages of their development in the bone marrow. However, the molecular mechanism underlying this regulation and whether it plays a role in B-cell homeostasis remain unknown. In the present study, we show that the differentiation of pre-B cells into immature and mature B cells is accompanied by modifications to the relative expression of chemokine receptors, with a two-fold downregulation of CXCR4 and upregulation of CCR7. We demonstrate that expression of CCR7 in B cells is involved in the selective inactivation of CXCR4, and that mature B cells from CCR7−/− mice display higher responsiveness to CXCL12 and improved retention in the bone marrow. We also provide molecular evidence supporting a model in which upregulation of CCR7 favors the formation of CXCR4–CCR7 heteromers, wherein CXCR4 is selectively impaired in its ability to activate certain G-protein complexes. Collectively, our results demonstrate that CCR7 behaves as a novel selective endogenous allosteric modulator of CXCR4.

Abstract Background Direct intra-articular injection (DIAI) of mesenchymal stem cells (MSCs) is a promising technique for cartilage repair. However, the repair process was hindered by the absence of scaffold and poor cell–matrix interactions. Methods In this study, we developed a pericellular collagen I coating (PCC) on MSCs. The overall performances of MSC-PCC homing, chondrogenic differentiation, and cartilage regeneration have been comprehensively evaluated in a New Zealand rabbit model. Firstly, we examined the morphology and physical characteristics of PCC. Secondly, MSC ex-vivo cartilage slice adhesion and in-vivo cartilage defect homing were observed using multiscale methods. Thirdly, the precartilage condensation of cell pellets formed by aggregation of MSCs was examined to evaluate the cartilage-inducing potential of PCC. Finally, the cartilage regeneration by DIAI of PCC-coated MSCs was observed and scored macroscopically and histologically. Results In general, the cell adhesion and homing assay revealed that PCC facilitated MSC adhesion on cartilage slices, enhancing MSC homing and retention to cartilage defect. This increased homing ratio was accompanied by an increasing cell–cell contact. Compared with naked MSCs, the cell pellets formed by PCC-coated MSCs exhibited more evident appearance of condensation. In pellets, cell–cell interaction has been significantly stimulated, inducing the expression of condensation marker N-cadherin, and subsequent chondrogenic marker collagen II and aggrecan. By 12 weeks after DIAI, cartilage defects have been repaired by MSCs to varying degrees. Overall, PCC significantly enhances the quality of cartilage regeneration judging from macroscopic observation, ICRS score, histological examination, and collagen type I, II, and X immunohistochemical staining. Conclusions The capacity and viability of MSCs can be enhanced by collagen I coating, which provides cues for enhancing cell homing and differentiation. Our method provides a novel strategy for stem cell therapy.

Research in migrant practices has recognised that home crystallises into multiple forms subject to constant re-enactment when viewed from the perspective of mobile populations such as nomads and refugees. In this article, we illustrate how artisan journeymen who went on the tramp around the turn of the 20th century performed home in multiple ways when on the road and at arrival in new locations. Using a historical example, we oppose the suggestion, which is common in contemporary migration and transnational studies that recent years have witnessed a paradigmatic new way of enacting belonging. Ultimately, the argument is that instead of idealising certain notions of the traveller, or ways of practicing home, we need to keep an eye to the real-life tensions of homing and the multiplicity through which it expresses; we need to understand homing as the performance of “belonging trouble.”

Abstract Background Endothelial progenitor cell (EPC) numbers are increased in septic patients and correlate with survival. In this study, we investigated, whether surface expression of chemokine receptors and other receptors important for EPC homing is upregulated by EPC from septic patients and if this is associated with clinical outcome. Methods Peripheral blood mononuclear cells from septic patients (n = 30), ICU control patients (n = 11) and healthy volunteers (n = 15) were isolated by Ficoll density gradient centrifugation. FACS-analysis was used to measure the expression of the CXC motif chemokine receptors (CXCR)-2 and − 4, the receptor for advanced glycation endproducts (RAGE) and the stem cell factor receptor c-Kit. Disease severity was assessed via the Simplified Acute Physiology Score (SAPS) II. The serum concentrations of vascular endothelial growth factor (VEGF), stromal cell-derived factor (SDF)-1α and angiopoietin (Ang)-2 were determined with Enzyme linked Immunosorbent Assays. Results EPC from septic patients expressed significantly more CXCR-4, c-Kit and RAGE compared to controls and were associated with survival-probability. Significantly higher serum concentrations of VEGF, SDF-1α and Ang-2 were found in septic patients. SDF-1α showed a significant association with survival. Conclusions Our data suggest that SDF-1α and CXCR-4 signaling could play a crucial role in EPC homing in the course of sepsis.

Abstract Nowadays, orthotopic liver transplantation is considered the most efficient approach to the end stage of chronic hepatic cirrhosis. Because of the limitations of orthotopic liver transplantation, stem cells are an attractive therapeutic option. Mesenchymal stem cells (MSCs) especially show promise as an alternative treatment for hepatic cirrhosis in animal models and during clinical trials. Nevertheless, the homing of transplanted MSCs to the liver occurs in limited numbers. Therefore, we review the strategies for enhancing the homing of MSCs, mainly via the delivery routes, optimizing cell culture conditions, stimulating the target sites, and genetic modification.

Abstract CXCR4 was the first receptor identified for CXCL12, but a second receptor, CXCR7, has also been described and its function in hematopoietic cells remains unknown. By inhibition of CXCR4 and/or CXCR7, we showed that CXCR7 participates in normal CD34+ and U937 cell migration and prevents downregulation of CXCR4 by CXCL12 stimulation. In addition, CXCR7 contributes to homing of acute myeloid leukemia and normal progenitor cells to the bone marrow and spleen of NOD/SCID mice. In summary, this study shows an essential role of CXCR7, together with CXCR4, in the control of normal and malignant hematopoietic cell migration and homing induced by CXCL12.

Conservation efforts addressing the impacts of habitat loss and fragmentation on movements must rely on operational definitions of land-cover types that are relevant to the behavioral decisions made by the species of interest. Travel costs, and ultimately landscape resistance (or permeability to movement) can be assessed through experiments standardizing the motivation of individuals to move across specific landscape elements, including habitat patches, the matrix, and their edges. So far, most studies modeling landscape permeability based on cost values have focused on habitat-specialist species and characterized landscape composition based on contrasting, human-defined cover types such as forest and open land. We experimentally evaluated the permeability to movement of different forest-cover types for the Ovenbird (Seiurus aurocapilla), a neotropical migratory species breeding in mature deciduous or mixed forest. We compared homing time and movement patterns of 60 radio-tracked males translocated over 500 m and released in untreated or partially harvested mature deciduous stands, as well as in conifer plantations, in northwestern New Brunswick, Canada. Although there was no strong effect of forest-cover type on homing time, path tortuosity, or travel speed, individuals released in conifer plantations tended to move faster and straighter than those released within untreated forest. Considering that translocated Ovenbirds have been shown to be less likely to return to capture sites in landscapes dominated by conifer plantations, our results suggest that they minimize time spent in inhospitable cover types. Responses to conifer plantation edges and similar interfaces may thus represent decisive components of time-based functional connectivity estimates. Hence, it appears that not all forest-cover types offer an equal resistance to Ovenbird movements and, consequently, a dichotomic habitat/non-habitat view may be too simplistic when assessing or modeling landscape permeability for passerine birds.

Homing was studied in the Forest dormouse, Dryomys nitedula. The distance of the experimental travels of trapped and marked dormice varied between the minimum (50 m) and the maximum (10 km). Fifty-seven experimental releases were carried out. Based on the distribution of 11 animal returns, a low probability of return was revealed from a distance of up to 5 km. The expected return probability was calculated using Furrer's formula. The time of absence from a place of capture was up to four days when transferred to a distance of up to 100 m, from four to seven days when the distance was up to 1000 m, and it began to grow exponentially after a transfer to a distance of more than 1 km. The return time increased nonlinearly with the increase in the transfer distance. This suggests that the displaced animals discover their home area as a result of random walks. [ABSTRACT FROM AUTHOR]

Unusual amongst dung beetles, Scarabaeus galenus digs a burrow that it provisions by making repeated trips to a nearby dung pile. Even more remarkable is that these beetles return home moving backwards, with a pellet of dung between their hind legs. Here, we explore the strategy that S. galenus uses to find its way home. We find that, like many other insects, they use path integration to calculate the direction and distance to their home. If they fail to locate their burrow, the beetles initiate a distinct looping search behaviour that starts with a characteristic sharp turn, we have called a 'turning point'. When homing beetles are passively displaced or transferred to an unfamiliar environment, they initiate a search at a point very close to the location of their fictive burrow—that is, a spot at the same relative distance and direction from the pick-up point as the original burrow. Unlike other insects, S. galenus do not appear to supplement estimates of the burrow location with landmark information. Thus, S. galenus represents a rare case of a consistently backward-homing animal that does not use landmarks to augment its path integration strategy. [ABSTRACT FROM AUTHOR]

Adequate homing is essential for the survival of any animal when it leaves its home to find prey or a mate. There are several strategies by which homing can be carried out: (a) retrace the outbound path; (b) use a 'cognitive map'; or (c) use path integration (PI). Here, I review the state of the art of research on spiders (Araneae) and whip spiders (Amblypygi) homing behaviour. The main strategy described in the literature as being used by these arachnids is PI. Behavioural and neural substrates of PI are described in a small group of spider families (Agelenidae, Lycosidae, Gnaphosidae, Ctenidae and Theraphosidae) and a whip spider family (Phrynidae). In spiders, the cues used to detect the position of the animal relative to its home are the position of the sun, polarized light patterns, web elasticity and landmarks. In whip spiders, the cues used are olfactory, tactile and, with a more minor role, visual. The use of a magnetic field in whip spiders has been rejected both with field and laboratory studies. Concerning the distance walked in PI, the possibility of using optic flow and idiothetic information in spiders is considered. The studies about outbound and inbound paths in whip spiders seem to suggest they do not follow the PI rules. As a conclusion, these arachnids' navigation relies on multimodal cues. We have detailed knowledge about the sensory origin (visual, olfactory, mechanosensory receptors) of neural information, but we are far from knowing the central neural structures where sensory information is integrated. [ABSTRACT FROM AUTHOR]

Pax7expression marks stem cells in developing skeletal muscles and adult satellite cells during homeostasis and muscle regeneration. The genetic determinants that control the entrance into the myogenic program and the appearance of PAX7+ cells during embryogenesis are poorly understood. SIX homeoproteins are encoded by the sine oculis-related homeobox Six1-Six6 genes in vertebrates. Six1, Six2, Six4 and Six5 are expressed in the muscle lineage. Here, we tested the hypothesis that Six1 and Six4 could participate in the genesis of myogenic stem cells. We show that fewer PAX7+ cells occupy a satellite cell position between the myofiber and its associated basal lamina in Six1 and Six4 knockout mice (s1s4KO) at E18. However, PAX7+ cells are detected in remaining muscle masses present in the epaxial region of the double mutant embryos and are able to divide and contribute to muscle growth. To further characterize the properties of s1s4KO PAX7+ cells, we analyzed their transcriptome and tested their properties after transplantation in adult regenerating tibialis anterior muscle. Mutant stem cells contribute to hypotrophic myofibers that are not innervated but retain the ability to self-renew. [ABSTRACT FROM AUTHOR]

Stem cell homing is a multistep endogenous physiologic process that is also used by exogenously administered hematopoietic stem and progenitor cells (HSPCs). This multistep process involves cell migration and is essential for hematopoietic stem cell transplantation. The process can be manipulated to enhance ultimate engraftment potential, and understanding stem cell homing is also important to the understanding of stem cell mobilization. Homing is also of potential importance in the recruitment of marrow mesenchymal stem and stromal cells (MSCs) to sites of injury and regeneration. This process is less understood but assumes importance when these cells are used for repair purposes. In this review, the process of HSPC and MSC homing is examined, as are methods to enhance this process. [ABSTRACT FROM AUTHOR]

Background: Ischaemic stroke has become the main cause of death and severe neurological disorders, for which effective restorative treatments are currently limited. While stem cell transplantation offers therapeutic potential through neural regeneration, this approach is associated with the challenges of limited applicable sources. Hair follicle stem cells (HFSCs) are multipotential cells that can differentiate into ectodermal and mesodermal lineages and proliferate for long periods. The therapeutic potentials of HFSCs have not been investigated in ischaemic stroke models, and therefore, in this study, we aimed to determine whether they could survive and migrate to ischaemic areas after a stroke attack. Methods: A rat model of middle cerebral artery ischaemia/reperfusion was established and intravenously administered HFSCs. The potential of HFSCs to migrate and differentiate into neuron-like cells as well as their ability to reduce the infarct size was evaluated. Rat brain tissue samples were collected 2 weeks after cell transplantation and analysed via TTC staining, immunofluorescence and immunohistochemistry methods. The data were statistically analysed and presented as the means ± standard deviations. Results: Intravenously administrated rat HFSCs were able to migrate to the penumbra where they expressed neuron-specific markers, reduced the infarct volume and promoted neurological recovery. Conclusion: HFSC transplantation has therapeutic potential for ischaemic stroke and is, therefore, worthy of further investigation toward possible clinical development for treating stroke patients. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common joint disease in the middle and old age group with obvious cartilage damage, and the regeneration of cartilage is the key to alleviating or treating OA. In stem cell therapy, bone marrow stem cell (BMSC) has been confirmed to have cartilage regeneration ability. However, the role of stem cells in promoting articular cartilage regeneration is severely limited by their low homing rate. Stromal cell‐derived factor‐1α (SDF‐1α) plays a vital role in MSC migration and involves activation, mobilization, homing and retention. So, we aim to develop SDF‐1α‐loaded microbubbles MB(SDF‐1α), and to verify the migration of BMSCs with the effect of ultrasound combined with MB(SDF‐1α) in vitro and in vivo. The characteristics of microbubbles and the content of SDF‐1α were examined in vitro. To evaluate the effect of ultrasound combined with chemotactic microbubbles on stem cell migration, BMSCs were injected locally and intravenously into the knee joint of the OA model, and the markers of BMSCs in the cartilage were detected. We successfully prepared MB(SDF‐1α) through covalent bonding with impressive SDF‐1α loading efficacy loading content. In vitro study, ultrasound combined with MB(SDF‐1α) group can promote more stem cell migration with highest migrating cell counts, good cell viability and highest CXCR4 expression. In vivo experiment, more BMSCs surface markers presented in the ultrasound combined with MB(SDF‐1α) group with or without exogenous BMSCs administration. Hence, ultrasound combined with MB(SDF‐1α) could promote the homing of BMSCs to cartilage and provide a novel promising therapeutic approach for OA. [ABSTRACT FROM AUTHOR]

Recent socio-political situations in the Middle East and elsewhere have resulted in a large number of refugees searching for new places to settle. To understand how a new place could become a home, the authors conducted qualitative research in the Netherlands. The study looked at the home experiences and (micro)homemaking practices of young Syrian refugees in an innovative housing project in Amsterdam. In this project, Dutch and Syrian young adults are housed together to foster integration. This article also looks at Boccagni's model for understanding immigrant live-in workers' homes. The authors further develop the model by introducing a mobility lens, which offers the possibility of elaborating on theoretical notions between now-and-then and here-and-there and the empirical findings derived from this study. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is a major cause of mortality and morbidity worldwide. Exosome therapies are promising for cardiac repair. Exosomes transfer cargo between cells, have high uptake by native cells and are ideal natural carriers for proteins and nucleic acids. Despite their proreparative potential, exosome production is dependent on parent cell state with typically low yields and cargo variability. Therefore, there is potential value in engineering exosomes to maximize their benefits by delivering customized, potent cargo for cardiovascular disease. Here, we outline several methods of exosome engineering focusing on three important aspects: optimizing cargo, homing to target tissue and minimizing clearance. Finally, we put these methods in context of the cardiac field and discuss the future potential of vesicle design. [ABSTRACT FROM AUTHOR]

Foetal onset hydrocephalus is a disease starting early in embryonic life; in many cases it results from a cell junction pathology of neural stem (NSC) and neural progenitor (NPC) cells forming the ventricular zone (VZ) and sub-ventricular zone (SVZ) of the developing brain. This pathology results in disassembling of VZ and loss of NSC/NPC, a phenomenon known as VZ disruption. At the cerebral aqueduct, VZ disruption triggers hydrocephalus while in the telencephalon, it results in abnormal neurogenesis. This may explain why derivative surgery does not cure hydrocephalus. NSC grafting appears as a therapeutic opportunity. The present investigation was designed to find out whether this is a likely possibility. HTx rats develop hereditary hydrocephalus; 30–40% of newborns are hydrocephalic (hyHTx) while their littermates are not (nHTx). NSC/NPC from the VZ/SVZ of nHTx rats were cultured into neurospheres that were then grafted into a lateral ventricle of 1-, 2- or 7-day-old hyHTx. Once in the cerebrospinal fluid, neurospheres disassembled and the freed NSC homed at the areas of VZ disruption. A population of homed cells generated new multiciliated ependyma at the sites where the ependyma was missing due to the inherited pathology. Another population of NSC homed at the disrupted VZ differentiated into βIII-tubulin+ spherical cells likely corresponding to neuroblasts that progressed into the parenchyma. The final fate of these cells could not be established due to the protocol used to label the grafted cells. The functional outcomes of NSC grafting in hydrocephalus remain open. The present study establishes an experimental paradigm of NSC/NPC therapy of foetal onset hydrocephalus, at the etiologic level that needs to be further explored with more analytical methodologies. [ABSTRACT FROM AUTHOR]

Most arachnids are central-place foragers that return to retreats or burrows after excursions to hunt. In general, arachnids are relatively large and accessible to behavioral and physiological investigations, and in several cases the animals have special sensory structures that facilitate homing. Here we review the mechanisms used by non-arachnid walking animals to return to specific sites and compare them to what is known for several groups of arachnids. Much of what we know about path integration, in which an animal estimates the angle and distance of a homeward vector using information gathered during an outbound journey, has been gleaned through systematic behavioral experiments on spiders. We focus on the most heavily studied spider models, highlighting the methodology used to deduce various aspects of the path integration machinery. We also highlight some work being done on longer range spider navigators, and emerging work with other arachnid groups. We provide additional thoughts concerning the evolution of homing systems and suggest promising leads for further investigation. [ABSTRACT FROM AUTHOR]

The trabecular meshwork (TM) is an ocular tissue that maintains intraocular pressure (IOP) within a physiologic range. Glaucoma patients have reduced TM cellularity and, frequently, elevated IOP. To establish a stem cell‐based approach to restoring TM function and normalizing IOP, human adipose‐derived stem cells (ADSCs) were induced to differentiate to TM cells in vitro. These ADSC‐TM cells displayed a TM cell‐like genotypic profile, became phagocytic, and responded to dexamethasone stimulation, characteristic of TM cells. After transplantation into naive mouse eyes, ADSCs and ADSC‐TM cells integrated into the TM tissue, expressed TM cell markers, and maintained normal IOP, outflow facility, and extracellular matrix. Cell migration and affinity results indicated that the chemokine pair CXCR4/SDF1 may play an important role in ADSC‐TM cell homing. Our study demonstrates the possibility of applying autologous or allogeneic ADSCs and ADSC‐TM cells as a potential treatment to restore TM structure and function in glaucoma. [ABSTRACT FROM AUTHOR]

Determining bee flight capacity is crucial for developing management strategies for bee conservation and/or crop pollination and purposes. In this study, we determined the flight distance of the stingless bee Melipona fasciculata using the radiofrequency identification (RFID) technology. For this, we conducted two translocation experiments using workers equipped with RFID microsensors: (1) release of bees at seven distances between 100 and 3000 m from experimental colonies in Belém, Brazil, and (2) at six distances between 1500 and 10,000 m at Carajás National Forest Reserve. Return rates of workers were negatively correlated to release distance, with typical flight distances of 2 km, but a maximum homing distance of 10 km. Use of RFID tags revealed how past experiments may have greatly underestimated homing abilities of stingless bees. [ABSTRACT FROM AUTHOR]