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Ischemic stroke is a major cause of mortality and disability worldwide, with limited treatment options available in clinical practice. The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function. Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect. Neural stem cells regulate multiple physiological responses, including nerve repair, endogenous regeneration, immune function, and blood-brain barrier permeability, through the secretion of bioactive substances, including extracellular vesicles/exosomes. However, due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation, limitations in the treatment effect remain unresolved. In this paper, we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke, review current neural stem cell therapeutic strategies and clinical trial results, and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells. We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells. [ABSTRACT FROM AUTHOR]

[INLINE:1] We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver” mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

Ischemic stroke is a major cause of mortality and disability worldwide, with limited treatment options available in clinical practice. The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function. Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect. Neural stem cells regulate multiple physiological responses, including nerve repair, endogenous regeneration, immune function, and blood-brain barrier permeability, through the secretion of bioactive substances, including extracellular vesicles/exosomes. However, due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation, limitations in the treatment effect remain unresolved. In this paper, we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke, review current neural stem cell therapeutic strategies and clinical trial results, and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells. We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.

Tissue engineering for spinal cord injury (SCI) remains a complex and challenging task. Biomaterial scaffolds have been suggested as a potential solution for supporting cell survival and differentiation at the injury site. However, different biomaterials display multiple properties that significantly impact neural tissue at a cellular level. Here, we evaluated the behavior of different cell lines seeded on chitosan (CHI), poly (ε-caprolactone) (PCL), and poly (L-lactic acid) (PLLA) scaffolds. We demonstrated that the surface properties of a material play a crucial role in cell morphology and differentiation. While the direct contact of a polymer with the cells did not cause cytotoxicity or inhibit the spread of neural progenitor cells derived from neurospheres (NPCdn), neonatal rat spinal cord cells (SCC) and NPCdn only attached and matured on PCL and PLLA surfaces. Scanning electron microscopy and computational analysis suggested that cells attached to the material's surface emerged into distinct morphological populations. Flow cytometry revealed a higher differentiation of neural progenitor cells derived from human induced pluripotent stem cells (hiPSC-NPC) into glial cells on all biomaterials. Immunofluorescence assays demonstrated that PCL and PLLA guided neuronal differentiation and network development in SCC. Our data emphasize the importance of selecting appropriate biomaterials for tissue engineering in SCI treatment. [ABSTRACT FROM AUTHOR]

Parkinson’s disease is a neurodegenerative condition characterized by motor impairments caused by the selective loss of dopaminergic neurons in the substantia nigra. Levodopa is an effective and well-tolerated dopamine replacement agent. However, levodopa provides only symptomatic improvements, without affecting the underlying pathology, and is associated with side effects after long-term use. Cell-based replacement is a promising strategy that offers the possibility to replace lost neurons in Parkinson’s disease treatment. Clinical studies of transplantation of human fetal ventral mesencephalic tissue have provided evidence that the grafted dopaminergic neurons can reinnervate the striatum, release dopamine, integrate into the host neural circuits, and improve motor functions. One of the limiting factors for cell therapy in Parkinson’s disease is the low survival rate of grafted dopaminergic cells. Different factors could cause cell death of dopaminergic neurons after grafting such as mechanical trauma, growth factor deprivation, hypoxia, and neuroinflammation. Neurotrophic factors play an essential role in the survival of grafted cells. However, direct, timely, and controllable delivery of neurotrophic factors into the brain faces important limitations. Different types of cells secrete neurotrophic factors constitutively and co-transplantation of these cells with dopaminergic neurons represents a feasible strategy to increase neuronal survival. In this review, we provide a general overview of the pioneering studies on cell transplantation developed in patients and animal models of Parkinson’s disease, with a focus on neurotrophic factor-secreting cells, with a particular interest in mesenchymal stromal cells; that co-implanted with dopaminergic neurons would serve as a strategy to increase cell survival and improve graft outcomes.

Lithium-ion battery (LIB) remanufacturing holds great potential for CO 2 savings, but there are challenges to productive disassembly. The demand to increase productivity in LIB production has resulted in a number of assembly methods and LIB designs that are unfavorable for automated disassembly. Disassembly by automation must handle a large number of variants. Automated disassembly processes must disassemble LIB and replace cells in a fully automated and non-destructive manner. The development of automated remanufacturing solutions is inevitable in order to repair and reuse LIB components in closed loops, and enable multiple life cycles for remanufactured LIBs. This paper proposes an automated remanufacturing process for LIBs. The proposed concept includes process and remanufactured product design for LIB packs. The proposed LIB pack design enables the separation of ultrasonic wire bonds to replace and reconnect defective cells from wire-bonded LIB packs. Both the process and LIB pack designs are evaluated using a use case, and the stability of cell separation and reconnection with ultrasonic welding is demonstrated. [ABSTRACT FROM AUTHOR]

The importance of energy supply and demand has been emphasized over the past few years. Renewable energy without regional bias continues to attract attention. The improvement of the economic feasibility of renewable energy leads to the expansion of the supply, and the global supply of solar modules is also rapidly increasing. Recently, the price of polysilicon for solar modules is also rising significantly. Interest in recycling waste modules is also increasing. However, the development of cost-effective treatment technology for solar modules that have reached the end of their commercial useful life is still insufficient. We are going to propose the standards necessary to restore and reuse so-called waste solar modules in a more eco-friendly and economical way. A crystalline solar module is an aggregate of individual solar cells. The technology is stable and has good durability. The efficiency of crystalline solar cells has dramatically improved in recent decades. The grade of cell that was mainly used two or three years ago will be discontinued soon. Therefore, electrical mismatch of the cells occurs while repairing an old-manufactured module with recently produced cells. In this paper, we experimentally verify how the increase in cell mismatch affects the module output. We intend to suggest the range of acceptable mismatches by analyzing the tendency. First of all, we repaired and restored the module in which all the existing cells were discontinued after about 10 years of production. The replacement cell had 16.94% higher output than the existing cells. After restoring the module, it was confirmed that the electrical mismatch loss of the cell in this range was very small, about 1.69%. Second, the mismatch loss was confirmed by manufacturing a module by mixing the two cells. The difference in output between the two cells was 5.56%. The mismatch loss compared to the predicted value based on the output of the individual cell and the actual value was very small, less than 0.76%. The long-term reliability results through the DH 1000 hr experiment on the sample that simulated the situation of repair, and the rest of the samples also showed a decrease in output up to 1.13%, which was not a problem. Finally, we hypothesized that a series-connected array should be constructed by reusing modules with different output classes. By cutting into 1/4, 1/3, and 1/2 of cells of the same grade, various unit module samples composed of 0.5 cells to 2.0 cells were manufactured and the output was measured. Electrical mismatch loss was tested by serially combining each unit module at various mismatch ratios. It was confirmed that the output loss in the three or more samples similarly exceeds about 10% with the mismatch ratio of 50% as the starting point. In the previous study, when the mismatch ratio was 70%, the output loss was about 17.98%. The output loss was 18.30% at 86.57%, 17.33% at 77.33%, and 14.37% at 75%. Considering that it is a value measured in a wide range, it is a result that is quite consistent with the results of previous studies. When the cell output difference was less than 50%, the electrical mismatch of the cell had no significant effect on the module output. When it exceeds that, a sudden output loss of 10% or more begins to occur. Consequently, the mismatch range of compatible cells should be less than 50%. If it exceeds that, not only output loss but also safety problems may occur due to heat generation. We can offer a range of interchangeable cell output power when crystalline solar modules are repaired and reused. By recycling modules with different outputs, you can provide a standard for those who want to use it by composing an array. By extending the lifespan of a solar module once used, it is expected that the generation of waste can be reduced from environmental point of view and the resources required to manufacture a new module can be saved from the resource-circulation point of view. [ABSTRACT FROM AUTHOR]

Recycling of problematic photovoltaic modules as raw materials requires considerable energy. The technology to restore cells in hotspot modules at a relatively low cost is more economical than replacing them with new modules. Moreover, a technology that restores power by replacing a cell-in-hotspot of a photovoltaic module with a new cell rather than replacing the whole module is useful for operating power plants. In particular, power plants that receive government subsidies have to use certified modules of specific models; the modules cannot be replaced with other modules. Before putting resources into module restoration, predicting the power of a module to be restored by replacing a cracked cell with a new cell is essential. Therefore, in this study, the module output amount after restoration was calculated using the previously proposed relative power loss analysis method and the recently proposed cell-to-module factor analysis method. In addition, the long-term degradation coefficient of the initial cell and the loss due to the electrical mismatch between the initial and new cell were considered. The output of the initial cell was estimated by inversely calculating the cell-to-module factor. The differences between the power prediction value and the actual experimental result were 1.12% and 3.20% for samples 190 A and 190 B, respectively. When the initial rating power and tolerance of the module were corrected, the differences decreased to 0.10% and 2.01%, respectively. The positive mismatch, which restores cells with a higher power, has no loss due to the reverse current; thus, the efficiency of the modules is proportional to the average efficiency of each cell. In this experiment, the electrical mismatches were only 0.37% and 0.34%. This study confirmed that even if a replacement cell has a higher power (<20%) than the existing cell, the power loss is not significantly affected, and heat generation of the existing normal cell is not observed. Hence, it was concluded that when some cells are damaged in a crystalline solar cell, the module could be restored by replacing only those cells instead of disposing of the entire module. However, for commercialization of the proposed method, a long-term reliability test of the module repaired using this method must be performed to confirm the results. Following this, recycling cells instead of recycling modules will be an economical and eco-friendly alternative. [ABSTRACT FROM AUTHOR]

Stem cells play a critical role in regulatory operations, overseeing tissue regeneration and tissue homeostasis. In this paper, a mathematical model is proposed and analyzed to study the impact of stem cell transplantation on the dynamical behavior of stroke therapy, which is assumed to be based on transplanting dead brain cells following a stroke. We transform the method of using hierarchical cell systems into a method of using different compartment variables by using ordinary differential equations, each of which elucidates a well-defined differentiation stage along with the effect of mature cells in improving the brain function after a stroke. Stem cells, progenitor cells, and the impacts of the stem cells transplanted on brain cells are among the variables considered. The model is studied analytically and solved numerically using the fourth-order Runge-Kutta method. We analyze the structure of equilibria, the ability of neural stem cells to proliferate and differentiate, and the stability properties of equilibria for stem cell transplantation. The model is considered to be stable after transplantation if the stem cells and progenitor cells differentiate into mature nerve cells in the brain. The results of the model analysis and simulation facilitate the identification of various biologically probable parameter sets that can explain the optimal time for stem cell replacement of damaged brain cells. Associating the classified parameter sets with recent experimental and clinical findings contributes to a better understanding of therapeutic mechanisms that promote the reconstitution of brain cells after an ischemic stroke.

Abstract Brain degeneration and damage is difficult to cure due to the limited endogenous repair capability of the central nervous system. Furthermore, drug development for treatment of diseases of the central nervous system remains a major challenge. However, it now appears that using human pluripotent stem cell‐derived neural cells to replace degenerating cells provides a promising cell‐based medicine for rejuvenation of brain function. Accordingly, a large number of studies have carried out preclinical assessments, which have involved different neural cell types in several neurological diseases. Recent advances in animal models identify the transplantation of neural derivatives from pluripotent stem cells as a promising path toward the clinical application of cell therapies [Stem Cells Transl Med 2019;8:681‐693; Drug Discov Today 2019;24:992‐999; Nat Med 2019;25:1045‐1053]. Some groups are moving toward clinical testing in humans. However, the difficulty in selection of valuable critical quality criteria for cell products and the lack of functional assays that could indicate suitability for clinical effect continue to hinder neural cell‐based medicine development [Biologicals 2019;59:68‐71]. In this review, we summarize the current status of preclinical studies progress in this area and outline the biological characteristics of neural cells that have been used in new developing clinical studies. We also discuss the requirements for translation of stem cell‐derived neural cells in examples of stem cell‐based clinical therapy.

The importance of energy supply and demand has been emphasized over the past few years. Renewable energy without regional bias continues to attract attention. The improvement of the economic feasibility of renewable energy leads to the expansion of the supply, and the global supply of solar modules is also rapidly increasing. Recently, the price of polysilicon for solar modules is also rising significantly. Interest in recycling waste modules is also increasing. However, the development of cost-effective treatment technology for solar modules that have reached the end of their commercial useful life is still insufficient. We are going to propose the standards necessary to restore and reuse so-called waste solar modules in a more eco-friendly and economical way. A crystalline solar module is an aggregate of individual solar cells. The technology is stable and has good durability. The efficiency of crystalline solar cells has dramatically improved in recent decades. The grade of cell that was mainly used two or three years ago will be discontinued soon. Therefore, electrical mismatch of the cells occurs while repairing an old-manufactured module with recently produced cells. In this paper, we experimentally verify how the increase in cell mismatch affects the module output. We intend to suggest the range of acceptable mismatches by analyzing the tendency. First of all, we repaired and restored the module in which all the existing cells were discontinued after about 10 years of production. The replacement cell had 16.94% higher output than the existing cells. After restoring the module, it was confirmed that the electrical mismatch loss of the cell in this range was very small, about 1.69%. Second, the mismatch loss was confirmed by manufacturing a module by mixing the two cells. The difference in output between the two cells was 5.56%. The mismatch loss compared to the predicted value based on the output of the individual cell and the actual value was very small, less than 0.76%. The long-term reliability results through the DH 1000 hr experiment on the sample that simulated the situation of repair, and the rest of the samples also showed a decrease in output up to 1.13%, which was not a problem. Finally, we hypothesized that a series-connected array should be constructed by reusing modules with different output classes. By cutting into 1/4, 1/3, and 1/2 of cells of the same grade, various unit module samples composed of 0.5 cells to 2.0 cells were manufactured and the output was measured. Electrical mismatch loss was tested by serially combining each unit module at various mismatch ratios. It was confirmed that the output loss in the three or more samples similarly exceeds about 10% with the mismatch ratio of 50% as the starting point. In the previous study, when the mismatch ratio was 70%, the output loss was about 17.98%. The output loss was 18.30% at 86.57%, 17.33% at 77.33%, and 14.37% at 75%. Considering that it is a value measured in a wide range, it is a result that is quite consistent with the results of previous studies. When the cell output difference was less than 50%, the electrical mismatch of the cell had no significant effect on the module output. When it exceeds that, a sudden output loss of 10% or more begins to occur. Consequently, the mismatch range of compatible cells should be less than 50%. If it exceeds that, not only output loss but also safety problems may occur due to heat generation. We can offer a range of interchangeable cell output power when crystalline solar modules are repaired and reused. By recycling modules with different outputs, you can provide a standard for those who want to use it by composing an array. By extending the lifespan of a solar module once used, it is expected that the generation of waste can be reduced from environmental point of view and the resources required to manufacture a new module can be saved from the resource-circulation point of view.

Stem cell therapy using human skin-derived neural precursors holds much promise for the treatment of stroke patients. Two main mechanisms have been proposed to give rise to the improved recovery in animal models of stroke after transplantation of these cells. First, the so called by-stander effect, which could modulate the environment during early phases after brain tissue damage, resulting in moderate improvements in the outcome of the insult. Second, the neuronal replacement and functional integration of grafted cells into the impaired brain circuitry, which will result in optimum long-term structural and functional repair. Recently developed sophisticated research tools like optogenetic control of neuronal activity and rabies virus monosynaptic tracing, among others, have made it possible to provide solid evidence about the functional integration of grafted cells and its contribution to improved recovery in animal models of brain damage. Moreover, previous clinical trials in patients with Parkinson’s Disease represent a proof of principle that stem cell-based neuronal replacement could work in humans. Our studies with in vivo and ex vivo transplantation of human skin-derived cells neurons in animal model of stroke and organotypic cultures of adult human cortex, respectively, also support the hypothesis that human somatic cells reprogrammed into neurons can get integrated in the human lesioned neuronal circuitry. In the present short review, we summarized our data and recent studies from other groups supporting the above hypothesis and opening new avenues for development of the future clinical applications.

Abstract Background Neurodegenerative disorders have a complex pathology and are characterized by a progressive loss of neuronal architecture in the brain or spinal cord. Neuroprotective agents have demonstrated promising results at the preclinical stage, but this has not been confirmed at the clinical stage. Thus far, no neuroprotective drug that can prevent neuronal degeneration in patients with neurodegenerative disorders is available. Main body Recent studies have focused on neurorestorative measures, such as cell-based therapy, rather than neuroprotective treatment. The utility of cell-based approaches for the treatment of neurodegenerative disorders has been explored extensively, and the results have been somewhat promising with regard to reversing the outcome. Because of their neural crest origin, ease of harvest, accessibility, ethical suitability, and potential to differentiate into the neurogenic lineage, dental-derived stem cells (DSCs) have become an attractive source for cell-based neurorestoration therapies. In the present review, we summarize the possible use of DSC-based neurorestoration therapy as an alternative treatment for neurodegenerative disorders, with a particular emphasis on the mechanism underlying recovery in neurodegenerative disorders. Conclusion Transplantation research in neurodegenerative diseases should aim to understand the mechanism providing benefits both at the molecular and functional level. Due to their ease of accessibility, plasticity, and ethical suitability, DSCs hold promise to overcome the existing challenges in the field of neurodegeneration through multiple mechanisms, such as cell replacement, bystander effect, vasculogenesis, synaptogenesis, immunomodulation, and by inhibiting apoptosis.

A large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach for the treatment of cardiovascular diseases. Since the first transplantation into human patients, several stem cell types have been applied in this field, including bone marrow derived stem cells, cardiac progenitors as well as embryonic stem cells and their derivatives. However, results obtained from clinical studies are inconsistent and stem cell-based improvement of heart performance and cardiac remodeling was found to be quite limited. In order to optimize stem cell efficiency, it is crucial to elucidate the underlying mechanisms mediating the beneficial effects of stem cell transplantation. Based on these mechanisms, researchers have developed different improvement strategies to boost the potency of stem cell repair and to generate the “next generation” of stem cell therapeutics. Moreover, since cardiovascular diseases are complex disorders including several disease patterns and pathologic mechanisms it may be difficult to provide a uniform therapeutic intervention for all subgroups of patients. Therefore, future strategies should aim at more personalized SC therapies in which individual disease parameters influence the selection of optimal cell type, dosage and delivery approach.

Adrenal insufficiency requires lifelong corticoid replacement therapies. However, current therapies are not able to replace the physiological circadian pattern of the adrenal cortex and are associated with many metabolic, vascular, neuroendocrine, and mental perturbations. Therefore, regenerative and more curative strategies would be desirable. In the current perspective, we describe emerging new regenerative therapies for the treatment of adrenal insufficiency. In particular, we discuss gene therapy and cell replacement strategies. Furthermore, we discuss how adrenal cells might be used as a source for regenerative therapies of nonadrenal neurodegenerative diseases such as Parkinson disease. [ABSTRACT FROM AUTHOR]

Glaucoma is a neurodegenerative eye disease that causes permanent vision impairment. The main pathological characteristics of glaucoma are retinal ganglion cell (RGC) loss and optic nerve degeneration. Glaucoma can be caused by elevated intraocular pressure (IOP), although some cases are congenital or occur in patients with normal IOP. Current glaucoma treatments rely on medicine and surgery to lower IOP, which only delays disease progression. First-line glaucoma medicines are supported by pharmacotherapy advancements such as Rho kinase inhibitors and innovative drug delivery systems. Glaucoma surgery has shifted to safer minimally invasive (or microinvasive) glaucoma surgery, but further trials are needed to validate long-term efficacy. Further, growing evidence shows that adeno-associated virus gene transduction and stem cell-based RGC replacement therapy hold potential to treat optic nerve fiber degeneration and glaucoma. However, better understanding of the regulatory mechanisms of RGC development is needed to provide insight into RGC differentiation from stem cells and help choose target genes for viral therapy. In this review, we overview current progress in RGC development research, optic nerve fiber regeneration, and human stem cell-derived RGC differentiation and transplantation. We also provide an outlook on perspectives and challenges in the field. [ABSTRACT FROM AUTHOR]

Glaucoma is a group of irreversible blinding eye diseases characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons. Currently, there is no effective method to fundamentally resolve the issue of RGC degeneration. Recent advances have revealed that visual function recovery could be achieved with stem cell-based therapy by replacing damaged RGCs with cell transplantation, providing nutritional factors for damaged RGCs, and supplying healthy mitochondria and other cellular components to exert neuroprotective effects and mediate transdifferentiation of autologous retinal stem cells to accomplish endogenous regeneration of RGC. This article reviews the recent research progress in the above-mentioned fields, including the breakthroughs in the fields of in vivo transdifferentiation of retinal endogenous stem cells and reversal of the RGC aging phenotype, and discusses the obstacles in the clinical translation of the stem cell therapy.

The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce a localized retinal detachment to perform the subretinal placement of the transplanted cell; (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.

BACKGROUND As the number of patients with end-stage lung disease continues to rise, there is a growing need to increase the limited number of lungs available for transplantation. Unfortunately, attempts at engineering functional lung de novo have been unsuccessful, and artificial mechanical devices have limited utility as a bridge to transplant. This difficulty is largely due to the size and inherent complexity of the lung; however, recent advances in cell-based therapeutics offer a unique opportunity to enhance traditional tissue-engineering approaches with targeted site- and cell-specific strategies. METHODS Human lungs considered unsuitable for transplantation were procured and supported using novel cannulation techniques and modified ex-vivo lung perfusion. Targeted lung regions were treated using intratracheal delivery of decellularization solution. Labeled mesenchymal stem cells or airway epithelial cells were then delivered into the lung and incubated for up to 6 hours. RESULTS Tissue samples were collected at regular time intervals and detailed histologic and immunohistochemical analyses were performed to evaluate the effectiveness of native cell removal and exogenous cell replacement. Regional decellularization resulted in the removal of airway epithelium with preservation of vascular endothelium and extracellular matrix proteins. After incubation, delivered cells were retained in the lung and showed homogeneous topographic distribution and flattened cellular morphology. CONCLUSIONS Our findings suggest that targeted cell replacement in extracorporeal organs is feasible and may ultimately lead to chimeric organs suitable for transplantation or the development of in-situ interventions to treat or reverse disease, ultimately negating the need for transplantation. [ABSTRACT FROM AUTHOR]

The neurons of the retina can be affected by a wide variety of inherited or environmental degenerations that can lead to vision loss and even blindness. Retinal ganglion cell (RGC) degeneration is the hallmark of glaucoma and other optic neuropathies that affect millions of people worldwide. Numerous strategies are being trialed to replace lost neurons in different degeneration models, and in recent years, stem cell technologies have opened promising avenues to obtain donor cells for retinal repair. Stem cell–based transplantation has been most frequently used for the replacement of rod photoreceptors, but the same tools could potentially be used for other retinal cell types, including RGCs. However, RGCs are not abundant in stem cell–derived cultures, and in contrast to the short‐distance wiring of photoreceptors, RGC axons take a long and intricate journey to connect with numerous brain nuclei. Hence, a number of challenges still remain, such as the ability to scale up the production of RGCs and a reliable and functional integration into the adult diseased retina upon transplantation. In this review, we discuss the recent advancements in the development of replacement therapies for RGC degenerations and the challenges that we need to overcome before these technologies can be applied to the clinic. Developmental Dynamics 248:118–128, 2019. © 2018 Wiley Periodicals, Inc. Key Findings: We summarize the current protocols to generate Retinal Ganglion Cells from pluripotent stem cell cultures.We review the current status of the transplantation methods and the challenges that we still need to overcome before these approaches can be translated to the clinic.We offer some avenues to overcome the current challenges. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) diseases are a leading cause of death and disability. Due to CNS neurons have no self-renewal and regenerative ability as they mature, their loss after injury or disease is irreversible and often leads to functional impairments. Unfortunately, therapeutic options for CNS diseases are still limited, and effective treatments for these notorious diseases are warranted to be explored. At present, stem cell therapy has emerged as a potential therapeutic strategy for improving the prognosis of CNS diseases. Accumulating preclinical and clinical evidences have demonstrated that multiple molecular mechanisms, such as cell replacement, immunoregulation and neurotrophic effect, underlie the use of stem cell therapy for CNS diseases. However, several issues have yet to be addressed to support its clinical application. Thus, this review article aims to summarize the role and underlying mechanisms of stem cell therapy in treating CNS diseases. And it is worthy of further evaluation for the potential therapeutic applications of stem cell treatment in CNS disease. [ABSTRACT FROM AUTHOR]

Pluripotent stem cells (embryonic stem cells, ESCs, and induced pluripotent stem cells, iPSCs) have the capacity to generate neural progenitors that are intrinsically patterned to undergo differentiation into specific neuronal subtypes and express in vivo properties that match the ones formed during normal embryonic development. Remarkable progress has been made in this field during recent years thanks to the development of more refined protocols for the generation of transplantable neuronal progenitors from pluripotent stem cells, and the access to new tools for tracing of neuronal connectivity and assessment of integration and function of grafted neurons. Recent studies in brains of neonatal mice or rats, as well as in rodent models of brain or spinal cord damage, have shown that ESC- or iPSC-derived neural progenitors can be made to survive and differentiate after transplantation, and that they possess a remarkable capacity to extend axons over long distances and become functionally integrated into host neural circuitry. Here, we summarize these recent developments in the perspective of earlier studies using intracerebral and intraspinal transplants of primary neurons derived from fetal brain, with special focus on the ability of human ESC- and iPSC-derived progenitors to reconstruct damaged neural circuitry in cortex, hippocampus, the nigrostriatal system and the spinal cord, and we discuss the intrinsic and extrinsic factors that determine the growth properties of the grafted neurons and their capacity to establish target-specific long-distance axonal connections in the damaged host brain.

A large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach for the treatment of cardiovascular diseases. Since the first transplantation into human patients, several stem cell types have been applied in this field, including bone marrow derived stem cells, cardiac progenitors as well as embryonic stem cells and their derivatives. However, results obtained from clinical studies are inconsistent and stem cell-based improvement of heart performance and cardiac remodeling was found to be quite limited. In order to optimize stem cell efficiency, it is crucial to elucidate the underlying mechanisms mediating the beneficial effects of stem cell transplantation. Based on these mechanisms, researchers have developed different improvement strategies to boost the potency of stem cell repair and to generate the "next generation" of stem cell therapeutics. Moreover, since cardiovascular diseases are complex disorders including several disease patterns and pathologic mechanisms it may be difficult to provide a uniform therapeutic intervention for all subgroups of patients. Therefore, future strategies should aim at more personalized SC therapies in which individual disease parameters influence the selection of optimal cell type, dosage and delivery approach. [ABSTRACT FROM AUTHOR]

The absence of effective and satisfactory treatments that contribute to repairing the dopaminergic damage caused by Parkinson’s Disease (PD) and the limited recovery capacity of the nervous system are troubling issues and the focus of many research and clinical domains. Recent advances in the treatment of PD through stem cell (SC) therapy have recognized their promising restorative and neuroprotective effects that are implicated in the potentiation of endogenous mechanisms of repair and contribute to functional locomotor improvement. Physical exercise (PE) has been considered an adjuvant intervention that by itself induces beneficial effects in patients and animal models with Parkinsonism. In this sense, the combination of both therapies could provide synergic or superior effects for motor recovery, in contrast with their individual use. This review aims to provide an update on recent progress and the potential effectiveness of SC transplantation and PE for the treatment of locomotor deficits in PD. It has reviewed the neuropathological pathways involved in the classical motor symptoms of this condition and the mechanisms of action described in experimental studies that are associated with locomotor enhancement through exercise, cellular transplantation, and their union in some neurodegenerative conditions. [ABSTRACT FROM AUTHOR]

Many human diseases relating to central nervous system (CNS) are mimicked in animal models to evaluate the efficacy of stem cell therapy. The therapeutic role of stem cells in animal models of CNS diseases include replacement of diseased or degenerated neuron, oligodendrocytes or astrocytes with healthy ones, secretion of neurotrophic factors and delivery of therapeutics/genes. Scaffolds can be utilized for delivering stem cells in brain. Sustained delivery of stem cells, lineage specific differentiation, and enhanced neuronal network integration are the hallmarks of scaffold mediated stem cell delivery in CNS diseases. This review discusses the therapeutic role, challenges and future perspectives of stem cell therapy in animal models of CNS diseases.