Activation Of Endogenous Stem Cells Research Articles

Treatment of Syringomyelia Characterized by Focal Dilatation of the Central Canal Using Mesenchymal Stem Cells and Neural Stem Cells.

Syringomyelia is a progressive chronic disease that leads to nerve pain, sensory dissociation, and dyskinesia. Symptoms often do not improve after surgery. Stem cells have been widely explored for the treatment of nervous system diseases due to their immunoregulatory and neural replacement abilities. In this study, we used a rat model of syringomyelia characterized by focal dilatation of the central canal to explore an effective transplantation scheme and evaluate the effect of mesenchymal stem cells and induced neural stem cells for the treatment of syringomyelia. The results showed that cell transplantation could not only promote syrinx shrinkage but also stimulate the proliferation of ependymal cells, and the effect of this result was related to the transplantation location. These reactions appeared only when the cells were transplanted into the cavity. Additionally, we discovered that cell transplantation transformed activated microglia into the M2 phenotype. IGF1-expressing M2 microglia may play a significant role in the repair of nerve pain. Cell transplantation can promote cavity shrinkage and regulate the local inflammatory environment. Moreover, the proliferation of ependymal cells may indicate the activation of endogenous stem cells, which is important for the regeneration and repair of spinal cord injury.

Perinatal Tissue-Derived Stem Cells: An Emerging Therapeutic Strategy for Challenging Neurodegenerative Diseases.

Over the past 20 years, stem cell therapy has been considered a promising option for treating numerous disorders, in particular, neurodegenerative disorders. Stem cells exert neuroprotective and neurodegenerative benefits through different mechanisms, such as the secretion of neurotrophic factors, cell replacement, the activation of endogenous stem cells, and decreased neuroinflammation. Several sources of stem cells have been proposed for transplantation and the restoration of damaged tissue. Over recent decades, intensive research has focused on gestational stem cells considered a novel resource for cell transplantation therapy. The present review provides an update on the recent preclinical/clinical applications of gestational stem cells for the treatment of protein-misfolding diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). However, further studies should be encouraged to translate this promising therapeutic approach into the clinical setting.

Nanotherapeutic and Stem Cell Therapeutic Strategies in Neurodegenerative Diseases: A Promising Therapeutic Approach.

Neurodegeneration is characterized by progressive, disabling, and incurable neurological disorders with the massive loss of specific neurons. As one of the most promising potential therapeutic strategies for neurodegenerative diseases, stem cell therapy exerts beneficial effects through different mechanisms, such as direct replacement of damaged or lost cells, secretion of neurotrophic and growth factors, decreased neuroinflammation, and activation of endogenous stem cells. However, poor survival and differentiation rates of transplanted stem cells, insufficient homing ability, and difficulty tracking after transplantation limit their further clinical use. The rapid development of nanotechnology provides many promising nanomaterials for biomedical applications, which already have many applications in neurodegenerative disease treatment and seem to be able to compensate for some of the deficiencies in stem cell therapy, such as transport of stem cells/genes/drugs, regulating stem cell differentiation, and real-time tracking in stem cell therapy. Therefore, nanotherapeutic strategies combined with stem cell therapy is a promising therapeutic approach to treating neurodegenerative diseases. The present review systematically summarizes recent advances in stem cell therapeutics and nanotherapeutic strategies and highlights how they can be combined to improve therapeutic efficacy for the treatment of neurodegenerative diseases.

Overview of risk factors for stress urinary incontinence and strategies in its prevention and treatment

Stress urinary incontinence is a medical problem that afflicts women worldwide. The causes can be mainly divided into 4 parts: increased abdominal pressure and chronic ischemia of pelvic floor muscles, endocrine changes, pelvic structural damages, inflammatory and consumptive states. The choice of prevention and treatment should also be based on a comprehensive assessment of individualized factors. Treatment techniques which are more minimally invasive or even non-invasive than surgery are currently a hot topic of research in the field of pelvic floor and urinary control, including laser and radiofrequency therapy, periurethral injection therapy, exogenous stem cell therapy and technology for activation of endogenous stem cells. They are expected to solve the clinical problem of stress urinary incontinence with a wider scope of application, lower trauma and fewer complications in the future.

Amniotic fluid stem cell administration can prevent epithelial injury from necrotizing enterocolitis.

Stem cell therapy has been proven to rescue intestinal injury and stimulate intestinal regeneration in necrotizing enterocolitis (NEC). Specifically, stem cells derived from amniotic fluid (AFSCs) and mesenchymal stem cells (MSCs) derived from bone marrow have shown promising results in the treatment of experimental NEC. This study aims to examine the effects of AFSCs and MSCs on the prevention of intestinal injury during experimental NEC. Supernatants from AFSC and MSC cultures were collected to perform proteomic analysis. Prior to NEC induction, mice received intraperitoneal injections of phosphate-buffered saline (PBS), 2 × 106 AFSCs, or 2 × 106 MSCs. We found that AFSCs grew faster than MSCs. Proteomic analysis indicated that AFSCs are primarily involved in cell development and growth, while MSCs are involved in immune regulation. Administering AFSCs before NEC induction decreased NEC severity and mucosal inflammation. Intestinal proliferation and endogenous stem cell activation were increased after AFSC administration. However, administering MSCs before NEC induction had no beneficial effects. This study demonstrated that AFSCs and MSCs have different protein release profiles. AFSCs can potentially be used as a preventative strategy for neonates at risk of NEC, while MSCs cannot be used. AFSCs and MSCs have distinct protein secretory profiles, and AFSCs are primarily involved in cell development and growth, while MSCs are involved in immune regulation. AFSCs are unique in transiently enhancing healthy intestinal epithelial cell growth, which offers protection against the development of experimental NEC. The prevention of NEC via the administration of AFSCs should be evaluated in infants at great risk of developing NEC or in infants with early signs of NEC.

Role of prostaglandin E2 in tissue repair and regeneration.

Tissue regeneration following injury from disease or medical treatment still represents a challenge in regeneration medicine. Prostaglandin E2 (PGE2), which involves diverse physiological processes via E-type prostanoid (EP) receptor family, favors the regeneration of various organ systems following injury for its capabilities such as activation of endogenous stem cells, immune regulation, and angiogenesis. Understanding how PGE2 modulates tissue regeneration and then exploring how to elevate the regenerative efficiency of PGE2 will provide key insights into the tissue repair and regeneration processes by PGE2. In this review, we summarized the application of PGE2 to guide the regeneration of different tissues, including skin, heart, liver, kidney, intestine, bone, skeletal muscle, and hematopoietic stem cell regeneration. Moreover, we introduced PGE2-based therapeutic strategies to accelerate the recovery of impaired tissue or organs, including 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitors boosting endogenous PGE2 levels and biomaterial scaffolds to control PGE2 release.

The Atrioventricular Junction: A Potential Niche Region for Progenitor Cells in the Adult Human Heart.

A stem cell niche is a microenvironment where stem cells reside in a quiescent state, until activated. In a previous rat model, we combined 5-bromo-2-deoxy-uridine labeling with activation of endogenous stem cells by physical exercise and revealed a distinct region, in the atrioventricular junction (AVj), with features of a stem cell niche. In this study, we aim to investigate whether a similar niche exists in the human heart. Paired biopsies from AVj and left ventricle (LV) were collected both from explanted hearts of organ donors, not used for transplantation (N = 7) and from severely failing hearts from patients undergoing heart transplantation (N = 7). Using antibodies, we investigated the expression of stem cell, hypoxia, proliferation and migration biomarkers. In the collagen-dense region of the AVj in donor hearts, progenitor markers, MDR1, SSEA4, ISL1, WT1, and hypoxia marker, HIF1-α, were clearly detected. The expression gradually decreased with distance from the valve. At the myocardium border in the AVj costaining of the proliferation marker Ki67 with cardiomyocyte nuclei marker PCM1 and cardiac Troponin-T (cTnT) indicated proliferation of small cardiomyocytes. In the same site we also detected ISL1+/WT1+/cTnT cells. In addition, heterogeneity in cardiomyocyte sizes was noted. Altogether, these findings indicate different developmental stages of cardiomyocytes below the region dense in stem cell marker expression. In patients suffering from heart failure the AVj region showed signs of impairment generally displaying much weaker or no expression of progenitor markers. We describe an anatomic structure in the human hearts, with features of a progenitor niche that coincided with the same region previously identified in rats with densely packed cells expressing progenitor and hypoxia markers. The data provided in this study indicate that the adult heart contains progenitor cells and that AVj might be a specific niche region from which the progenitors migrate at the time of regeneration.

MicroRNAs and Regeneration in Animal Models of CNS Disorders.

microRNAs (miRNAs) are recently identified small RNA molecules that regulate gene expression and significantly influence the essential cellular processes associated with CNS repair after trauma and neuropathological conditions including stroke and neurodegenerative disorders. A number of specific miRNAs are implicated in regulating the development and propagation of CNS injury, as well as its subsequent regeneration. The review focuses on the functions of the miRNAs and their role in brain recovery following CNS damage. The article introduces a brief description of miRNA biogenesis and mechanisms of miRNA-induced gene suppression, followed by an overview of miRNAs involved in the processes associated with CNS repair, including neuroprotection, neuronal plasticity and axonal regeneration, vascular reorganization, neuroinflammation, and endogenous stem cell activation. Specific emphasis is placed on the role of multifunctional miRNA miR-155, as it appears to be involved in multiple neurorestorative processes during different CNS pathologies. In association with our own studies on miR-155, I introduce a new and unexplored approach to cerebral regeneration: regulation of brain tissue repair through a direct modulation of specific miRNA activity. The review concludes with discussion on the challenges and the future potential of miRNA-based therapeutic approaches to CNS repair.

Investigating Nrg1 Signaling in the Regenerating Axolotl Spinal Cord Using Multiplexed FISH.

Amputation of a salamander tail leads to functional spinal cord regeneration through activation of endogenous stem cells. Identifying the signaling pathways that control cell proliferation in these neural stem cells will help elucidate the mechanisms underlying the salamander's regenerative ability. Here, we show that neuregulin 1 (Nrg1)/ErbB2 signaling is an important pathway in the regulation of neural stem cell proliferation in the spinal cord of the axolotl salamander (Ambystoma mexicanum). Simultaneous localization of nrg1 mRNA and Nrg1 protein was performed by utilizing a hybridization chain reaction fluorescence in situ hybridization (FISH) methodology in tissue sections. Multiplexed FISH also permitted the phenotyping of multiple cell types on a single fixed section allowing the characterization of mRNA expression, protein expression, and tissue architecture. Pharmacological inhibition of ErbB2 showed that intact Nrg1/ErbB2 signaling is critical for adult homeostatic regeneration as well as for injury-induced spinal cord regeneration. Overall, our results highlight the importance of the NRG1/ErbB2 signaling pathway in neural stem cell proliferation in the axolotl.

Stem Cells: A New Hope for Hearing Loss Therapy.

Permanent hearing loss was considered which cannot be cured since cochlear hair cells and primary afferent neurons cannot be regenerated. In recent years, due to the in-depth study of stem cell and its therapeutic potential, regenerating auditory sensory cells is made possible. By using two strategies of endogenous stem cell activation and exogenous stem cell transplantation, researchers hope to find methods to restore hearing function. However, there are complex factors that need to be considered in the in vivo application of stem cell therapy, such as stem cell-type choice, signaling pathway regulations, transplantation approaches, internal environment of the cochlea, and external stimulation. After years of investigations, some theoretic progress has been made in the treatment of hearing loss using stem cells, but there are also many problems which limited its application that need to be solved. Understanding the future perspective of stem cell therapy in hearing loss, solving the encountered problems, and promoting its development are the common goals of audiological researchers. In this review, we present critical experimental findings of stem cell therapy on treatment of hearing loss and intend to bring hope to researchers and patients.

Perspectives of pharmacological intervention promoting liver regeneration

Effective drug therapy promoting liver regeneration is a challenging goal in pharmacotherapy of liver diseases. Several plant phytochemicals recommended in traditional medicine from over hundred plants have been investigated for its use in various liver disorders. Regeneration of injured liver depend on a proliferative potential of mature hepatocytes as well as different subsets of intrahepatic and extrahepatic stem/progenitor cells. In clinical trials a stem cell therapy resulted in a limited improvement of liver functions. Animal studies have demonstrated the involvement of bone marrow-derived stem/progenitor cells in liver regeneration. For this reason, the pharmacological activation of endogenous stem cells and pharmacological control of macrophage phenotypic polarization could be an effective method of mobilizing progenitor cells to injured liver.

Enhanced ACL Graft Incorporation by Novel Minimally Invasive Activation of Endogenous Stem Cells

Objectives:The ultimate healing of a ligament graft to bone is a lengthy process that results in reparative tissue that is distinctly different from a native ligament insertion. This known structural aberration results in inferior biomechanical properties and can contribute significantly to recurrent injury as well as compromised function. Thus, technology allowing for accelerated biologic incorporation as well as the recapitulation of a native insertion would be of great benefit to patients. We hypothesized that the treatment of anterior cruciate ligament (ACL) reconstruction bone tunnels with bone morphogenetic protein (BMP) DNA combined with a pulse of ultrasound (US) energy would lead to activation of endogenous stem cells and result in enhanced graft incorporation.Methods:Soft tissue allograft ACL reconstruction was performed in nine mini-pigs using cortical screw post fixation. A collagen scaffold was added to the terminus of each tendon graft limb contained within the corresponding bone tunnel. On post-operative day 14, a lipid microsphere solution containing DNA encoding either green fluorescence protein (GFP, n=3 pigs) or BMP-6 (n=6 pigs) was delivered into the bone tunnels percutaneously under fluoroscopic guidance. The bone tunnels in the US treated group were then immediately treated with a transcutaneous US energy pulse at the site of the bone tunnels, whereas the control group did not receive US delivery. At five days post-treatment the cells occupying the bone tunnels of the GFP treated pigs (n=3) were harvested and subjected to fluorescence-activated cell sorting (FACS) analysis to assess for expression of GFP as well as known mesenchymal stem cell (MSC) markers (CD29, CD44, CD90). Six weeks post-treatment the BMP/US treated pigs (n=3) and control pigs (n=3) were sacrificed and their knee joints were scanned using microCT. Biomechanical testing of anterior-posterior (AP) knee laxity was performed via application of sinusoidal AP-directed shear loads for 12 cycles. Load to failure was assessed by removal of the joint capsule, menisci, collateral ligaments, and the PCL leaving only the ACL graft intact. The tibia and femur were then mounted on a universal material testing machine with a 5kN load cell and distracted until failure of the ACL graft or graft-bone interface.Results:FACS analysis done 5 days after GFP gene delivery showed that 40-50% of the cells occupying the US treated bone tunnels expressed GFP and this was significantly more than the cells in untreated bone tunnels (p< 0.05). In addition, 12-22% of the cells in the bone tunnels expressed MSC markers. Quantification of bone volume in ACL reconstruction tunnels showed significantly higher values in BMP-6/US treated animals (fig 1A,B,C; *p<0.05, t-test). AP laxities at ±20N of BMP-6/US treated pigs were lower than untreated pigs (fig 1D). The linear stiffness (fig 1E) and maximum load to failure (fig 1F) were both significantly higher than untreated pigs, demonstrating stronger graft-bone integration among the treated animals. (*p<0.05, t-test).Conclusion:Endogenous stem cell gene expression can be altered in a large animal model via novel minimally invasive techniques and this can result in enhanced ligament biomechanical properties. Minimally invasive biologic technology such as this would likely be of significant benefit to the treatment of patients undergoing ligament reconstruction procedures and more research regarding these technologies is certainly warranted.

Resveratrol pre- and post-treatment in doxorubicin-induced cardiac injury in relation to endogenous stem cell activation

Background: Doxorubicin (DOX), is a highly efficient anti-neoplastic drug used for treatment of solid tumors includingbreast cancer (BC). Resveratrol (RES) is considered an interesting molecule in hormone dependent cancer therapy. Stem cell activation may induce less cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of cardiomyocytes. Materials and Methods: Twenty seven adult male albino rats, were divided into: control group including 6 rats, group II (DOX group) including 7 rats that received intraperitoneal (IP) injection with DOX 3 mg /kg 3 times a week for 2 weeks. Group III (RES post-treatment group) included 7 rats that were injected with DOX followed by 50 mg/Kg RES daily orally for another 2 weeks. Group IV (RES pretreatment group) included 7 rats that were injected with DOX and received concomitantly 50 mg/Kg RES daily orally for 2 weeks and left untreated for another 2 weeks. By the end of the 4th week all animals were sacrificed. Cardiac muscle specimens were subjected to histological, immunohistochemical, morphometric and serological studies. Results: Myocardial injury appeared as obvious congestion, apoptosis, degeneration, increased collagen fibers content,obvious caspase3 expression and minimal proliferating cell nuclear antigen (PCNA) +ve and CD44 +ve expression in DOX group. Regression of the previous changes was more remarkable in group IV than in group III except for PCNA and CD44 expression that was more obvious in both treatment groups.Conclusion: RES proved amelioration of DOX induced myocardial injury that was more noticeable in RES early administration. RES post-treatment might have been more efficient if longer duration was applied.

The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues.

Endothelial progenitor cells (EPCs) derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regeneration in musculoskeletal and neural tissues including the bone, skeletal muscle, ligaments, spinal cord, and peripheral nerves. EPCs can be mobilized from bone marrow and recruited to injured tissue to contribute to neovascularization and tissue repair. In addition, EPCs or stem cell populations containing EPCs promote neovascularization and tissue repair through their differentiation to endothelial cells or tissue-specific cells, the upregulation of growth factors, and the induction and activation of endogenous stem cells. Human peripheral blood CD34(+) cells containing EPCs have been used in clinical trials of bone repair. Thus, EPCs are a promising cell source for the treatment of musculoskeletal and neural tissue injury.

Exogenous stem cells pioneer a biobridge to the advantage of host brain cells following stroke: New insights for clinical applications.

Stroke continues to maintain its status as one of the top causes of mortality within the United States. Currently, the only Food and Drug Administration (FDA)-approved drug in place for stroke patients, tissue plasminogen activator (tPA), has a rigid therapeutic window, closing at approximately 4.5 h after stroke onset. Due to this short time frame and other restrictions, such as any condition that increases a patient's risk for hemorrhaging, it has been predicted that <5% of ischemic stroke patients benefit from tPA. Given that rehabilitation therapy remains the only other option for stroke victims, there is a clear unmet clinical need for treatment available for the remaining 95%. While still considered an experimental treatment, the utilization of stem cell therapies for stroke holds consistent promise. Copious preclinical studies report the capacity for transplanted stem cells to rescue the brain parenchyma surrounding the stroke-induced infarct core. At present, the exact mechanisms in which stem cells contribute a robust therapeutic benefit remains unclear. Following stem cell administration, researchers have observed cell replacement, an increase in growth factors, and a reduction in inflammation. With a deeper understanding of the precise mechanism of stem cells, these therapies can be optimized in the clinic to afford the greatest therapeutic benefit. Recent studies have depicted a unique method of endogenous stem cell activation as a result of stem cell therapy. In both traumatic brain injury and stroke models, transplanted mesenchymal stromal cells (MSCs) facilitated a pathway between the neurogenic niches of the brain and the damaged area through extracellular matrix remodeling. The biobridge pioneered by the MSCs was utilized by the endogenous stem cells, and these cells were able to travel to the damaged areas distal to the neurogenic niches, a feat unachievable without prior remodeling. These studies broaden our understanding of stem cell interactions within the injured brain and help to guide both researchers and clinicians in developing an effective stem cell treatment for stroke. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors’ experiences.

Mesenchymal stem cells promote augmented response of endogenous neural stem cells in spinal cord injury of rats

Traumatic spinal cord injury results in severe neurological deficits, mostly irreversible. The cell therapy represents a strategy for treatment particularly with the use of stem cells with satisfactory results in several experimental models. The aim of the study was to compare the treatment of spinal cord injury (SCI) with and without mesenchymal stem cells (MSC), to investigate whether MSCs migrate and/or remain at the site of injury, and to analyze the effects of MSCs on inflammation, astrocytic reactivity and activation of endogenous stem cells. Three hours after SCI, animals received bone marrow-derived MSCs (1×107 in 1mL PBS, IV). Animals were euthanized 24 hours, 7 and 21 days post-injury. The MSC were not present in the site of the lesion and the immunofluorescent evaluation showed significant attenuation of inflammatory response with reduction in macrophages labeled with anti-CD68 antibody (ED1), decreased immunoreactivity of astrocytes (GFAP+) and greater activation of endogenous stem cells (nestin+) in the treated groups. Therefore, cell transplantation have a positive effect on recovery from traumatic spinal cord injury possibly due to the potential of MSCs to attenuate the immune response.

Changing Paradigms in Cranio-Facial Regeneration: Current and New Strategies for the Activation of Endogenous Stem Cells.

Craniofacial area represent a unique district of human body characterized by a very high complexity of tissues, innervation and vascularization, and being deputed to many fundamental function such as eating, speech, expression of emotions, delivery of sensations such as taste, sight, and earing. For this reasons, tissue loss in this area following trauma or for example oncologic resection, have a tremendous impact on patients' quality of life. In the last 20 years regenerative medicine has emerged as one of the most promising approach to solve problem related to trauma, tissue loss, organ failure etc. One of the most powerful tools to be used for tissue regeneration is represented by stem cells, which have been successfully implanted in different tissue/organs with exciting results. Nevertheless, both autologous and allogeneic stem cell transplantation raise many practical and ethical concerns that make this approach very difficult to apply in clinical practice. For this reason different cell free approaches have been developed aiming to the mobilization, recruitment, and activation of endogenous stem cells into the injury site avoiding exogenous cells implant but instead stimulating patients' own stem cells to repair the lesion. To this aim many strategies have been used including functionalized bioscaffold, controlled release of stem cell chemoattractants, growth factors, BMPs, Platelet–Rich-Plasma, and other new strategies such as ultrasound wave and laser are just being proposed. Here we review all the current and new strategies used for activation and mobilization of endogenous stem cells in the regeneration of craniofacial tissue.

Abstract W P89: Functional Recovery Depends on Donor Age after Stem Cell Transplantation for Stroke

Introduction: Cell transplantation therapy hold great potential to improve impairments after cerebral ischemia. However, it is still unclear whether the donor age affects functional recovery after cerebral ischemia. Here, we investigate the hypothesis that donor age (young vs. old) drastically affects the repair mechanism after cell transplantation for stroke. Materials and methods: Male Sprague Dawley rats were subjected to transient middle cerebral artery occlusion. At 24 hours after stroke, rats were randomly assigned to receive PBS (control), human mesenchymal stem cells (MSC) derived from 24 years old man (young MSC) and MSC derived from 64 years old man (old MSC) via internal carotid artery. Behavioral recovery was assessed with modified Neurological severity score (mNSS) until 21 days after stroke. Animals were euthanized at 21 days, and histological analysis was performed regarding inflammatory reaction, neovascularization and endogenous stem cell activation. Result: Young MSC showed an significant recovery in mNSS (3.7±0.6) compared with control (6.1±0.5) and old MSC (5.2±0.7) at 21 days after stroke (P&lt;0.01). In histological analysis, infarct volume was not significantly different among the groups. However, IBA-1 positive microglia was significantly inhibited in young MSC (9.3±5.9%) compared with control (22.1±13.1%) and old MSC (15.2%±14.2%) both in the peri-infarct cortex and striatum (P&lt;0.01). Moreover, RECA-1 positive vessels significantly increased in young MSC (5.4±1.1%) compared with control (5.0±1.6%) and old MSC (4.6%±1.5%) in the peri-infarct cortex (P&lt;0.01). Interestingly, Young MSC showed massive GFAP positive reactive astrocyte running radially into the peri-infarct area with Musashi-1 (Msi-1) positive neural progenitor cells. Conclusion: Donor age drastically affect the host environment, endogenous progenitor cell activation and functional recovery after cell transplantation for stroke.

Cell replacement therapy: Lessons from teleost fish

Many disorders of the CNS are characterized by a massive loss of neurons. A promising therapeutic strategy to cure such conditions is based on the activation of endogenous stem cells. Implementation of this strategy will benefit from a better understanding of stem cell dynamics and the local CNS microenvironment in regeneration-competent vertebrate model systems. Using a spinal cord injury paradigm in zebrafish larvae, Briona and Dorsky (2014) have provided evidence for the existence of two distinct neural stem cell populations. One population has the characteristics of radial glia and expresses the homeobox transcription factor Dbx. The other lacks Dbx but expresses Olig2. These results are placed in the context of other studies that also support the notion of heterogeneity of adult stem cells in the CNS. The implication that differences among stem cell populations, in combination with specific factors from the local cellular microenvironment, might have a decisive impact on the fate choices of the new cells, is discussed. Reviewed evidence suggests that rather few modifications in the signaling pathways involved in the control of stem cell behavior have led, in the course of evolution, to the pronounced differences between mammals and regeneration-competent organisms. As a consequence, rather minor pharmacological manipulations may be sufficient to reactivate the hidden neurogenic potential of the mammalian CNS, and thus make it available for therapeutic applications.

O12: Exercise training restores the regenerative potential of injured skeletal muscle via activation of endogenous stem cells

O12: Exercise training restores the regenerative potential of injured skeletal muscle via activation of endogenous stem cells