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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.

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

The home is a unique location in the life of humans and animals. In rats, home presents itself as a multicompartmental space that involves integrating navigation through subspaces. Here we embedded the laboratory rat's home cage in the arena, while recording neurons in the animal's parasubiculum and medial entorhinal cortex, two brain areas encoding the animal's location and head direction. We found that head direction signals were unaffected by home cage presence or translocation. Head direction cells remain globally stable and have similar properties inside and outside the embedded home. We did not observe egocentric bearing encoding of the home cage. However, grid cells were distorted in the presence of the home cage. While they did not globally remap, single firing fields were translocated toward the home. These effects appeared to be geometrical in nature rather than a home-specific distortion and were not dependent on explicit behavioral use of the home cage during a hoarding task. Our work suggests that medial entorhinal cortex and parasubiculum do not remap after embedding the home, but local changes in grid cell activity overrepresent the embedded space location and might contribute to navigation in complex environments. NEW & NOTEWORTHY Neural findings in the field of spatial navigation come mostly from an abstract approach that separates the animal from even a minimally biological context. In this article we embed the home cage of the rat in the environment to address some of the complexities of natural navigation. We find no explicit home cage representation. While both head direction cells and grid cells remain globally stable, we find that embedded spaces locally distort grid cells. [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]

Homing behavior for autonomous underwater vehicles (AUVs) is vital for autonomous docking and indispensable for recovery of vehicles in logistically difficult or hazardous conditions. Homing to a single acoustic beacon is a low-logistics solution to this engineering challenge. A homing application has been developed in C++ that applies a multilateration-based localization algorithm to estimate transponder location for homing. Mission oriented operating suite interval programming (MOOS-IvP) was implemented as a backseat driver on a Teledyne Gavia AUV to enhance the AUV with adaptive maneuvering capabilities; thus, enabling mission waypoints to be dynamically updated by the homing application (pHomeToBeacon) through the MOOS database and a developed iGavia crewmember. To demonstrate MOOS-IvP-GAVIA and homing capabilities using this first-principles approach to localization, field trials were undertaken in Kópavogur, Iceland, in June 2015 and proved consistent homing to a single beacon within 15 m accuracy. These trials were an industry-first of deploying a user-developed application on MOOS-IvP-GAVIA and of having a Gavia enhanced with adaptive maneuvering capabilities for homing. This new capability enables Gavia AUV to be used as a platform for future developer-led autonomy and applications. Ultimately, pHomeToBeacon will enable any AUV enhanced with MOOS-IvP to use acoustics to home to a surface vessel (stationary or underway) in preparation for autonomous subsea docking and recovery. [ABSTRACT FROM AUTHOR]

In the event of a failure that will prevent an Autonomous Underwater Vehicle (AUV) from executing a specified task, the vehicle must be recovered safely to avoid further damage to itself or to other vehicles/agents in the neighbourhood. Motivated by this operational requirement, this work presents an optimal fault-tolerant controller to drive an underactuated AUV to a recovery point (so-called automatic homing manoeuvre). The case of a critical failure that leaves only one of two stern thrusters available to drive it to the desired recovery area is considered. The control law proposed relies on the use of a Fourier series-based strategy to compute the control action as a function of the relative orientation of the vehicle with respect to the target recovery point. Energy consumption is also considered in the proposed control law, so that an appropriate trade-off can be achieved between reaching the destination faster and reducing the energy consumed as a function of mission requirements and vehicle specifications. The stability and convergence of the proposed scheme are demonstrated analytically, a comparison with MPC scheme is shown and simulation examples illustrate how the control law effectively drives the vehicle to a neighbourhood of the desired target point even in the presence of unknown constant currents. • Fault-tolerant control designed to steer an underactuated AUV with a single thruster. • Control law based on Fourier series and relative orientation between vehicle and target. • Vehicle battery energy consumption is analysed and optimised. • Trade-off solutions between time and energy consumption are proposed. • Stability and convergence of the proposed control law are analytically demonstrated. [ABSTRACT FROM AUTHOR]

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.

INTRODUCTIONWilliam Bevis has argued that, whereas the classic American novel tells a story of “leaving,” in which characters find growth and fulfillment away from the homes they grew up in, the typical Native American novel is based around “homing.” In homing stories, the characters do not “find themselves” through independence but rather discover value and meaning by returning to their homes, pasts, and people. Although Bevis’s notion provides insight into many Native American works, one novel calling for a somewhat different approach is Louise Erdrich’s Tracks. Although notions of “leaving” and “homing” are central to Tracks, they operate in ways far more complex than Bevis’s view suggests.Since the novel’s 1988 publication, scholars have probed its depictions of characters losing, reclaiming, searching for, and finding home. Most have focused on the displacement and marginality the characters experience. Tracks has been described as “a novel entirely haunted by historical dispossession” in which the characters experience “dislocation from their heritage, their environment, and themselves.” A number of scholars have argued that displacement is manifested in the novel thematically and in the disparate voices and multiple perspectives it employs as narrative strategies.This concern with displacement obscures the fact that the novel is about losing home and about finding it. As Tom Berninghausen has pointed out, Erdrich’s characters are working toward “coming home in a social sense, being at home in the tribe’s history, and returning to the particular landscape that is home.” Lydia A. Schultz and E. Shelley Reid have disputed the suggestion that the novel’s narrative discontinuities reflect chaos and dispossession in the lives of the Anishinaabe, arguing instead that they represent the multivocalic strategies of traditional Anishinaabe storytelling—that is, they reflect continuity rather than disruption of Anishinaabe culture. Gloria Bird has pointed out that, although many of Erdrich’s characters live on the margins of society, they are people for whom those margins are home. Similarly, Pauline Woodward writes that Erdrich “offers a new rendering of community” concentrating on the endurance of the Anishinaabe even through the discontinuity they experience. Forces for and movements toward homing are intricately interwoven with energies and actions toward displacement throughout Tracks.

Procellariiform seabirds (petrels, albatrosses and shearwaters) navigate vast distances over seemingly featureless ocean habitat by mechanisms that are not well understood. These birds have large olfactory bulbs, and the use of smell has been implicated in both foraging and homing behavior. While many olfactory cues relevant to these behaviors have been identified, ammonia is a potentially significant, biogenic, scented compound that has not been studied in this context. Ammonium (NH4+) constitutes a primary waste product produced by many of the prey species on which procellariiforms forage. Nitrogen waste products, including volatilized ammonia (NH3) also scent the terrestrial landscape of sub-Antarctic islands where newly breeding procellariiform seabirds recruit and raise their young. Since an ability to smell ammonia may be relevant to both prey detection and locating colonies or islands, we used a non-invasive, behavioral assay to examine whether this scented compound is detectable by a candidate test species, the blue petrel Halobaena caerulea Gmelin. Our results suggest that these birds can detect volatilized ammonia within a concentration range that they may naturally encounter (10(-11) to 10(-5) M), and point to ammonia as a potential signal molecule in the sub-Antarctic.

Cord blood (CB) has been used as a viable source of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) in over 35,000 clinical hematopoietic cell transplantation (HCT) efforts to treat the same variety of malignant and non-malignant disorders treated by bone marrow (BM) and mobilized peripheral blood (mPB) using HLA-matched or partially HLA-disparate related or unrelated donor cells for adult and children recipients. This review documents the beginning of this clinical effort that started in the 1980’s, the pros and cons of CB HCT compared to BM and mPB HCT, and recent experimental and clinical efforts to enhance the efficacy of CB HCT. These efforts include means for increasing HSC numbers in single CB collections, expanding functional HSCs ex vivo, and improving CB HSC homing and engraftment, all with the goal of clinical translation. Concluding remarks highlight the need for phase I/II clinical trials to test the experimental procedures that are described, either alone or in combination.

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.