• Cancer
• Cell-based therapies
• Exosomes
• Immunomodulation
• Mesenchymal stem cells

• Humans
• Neoplasms/therapy
• Neoplasms/pathology
• Neoplasms/immunology
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/physiology
• Mesenchymal Stem Cells/immunology
• Mesenchymal Stem Cell Transplantation/methods
• Animals
• Cell Differentiation

• Ischemic stroke
• death
• mesenchymal stem cells
• progenitor cells
• stem cell therapy.
• stem cells

• Humans
• Ischemic Stroke/therapy
• Mesenchymal Stem Cell Transplantation/methods
• Network Meta-Analysis
• Treatment Outcome
• Stem Cell Transplantation/methods
• Bone Marrow Cells/cytology
• Randomized Controlled Trials as Topic

• 2018YFA0108604, 2018YFA0108603 National Key Research & Development Program of China
• 2018HXFH008 Clinical Incubation Program of West China Hospital

• Biomedical technology
• Neuronal plasticity
• Rehabilitation
• Stroke
• Stroke rehabilitation

• Humans
• Stroke Rehabilitation
• Stroke/therapy
• Brain
• Neuronal Plasticity/physiology
• Cerebral Cortex
• Recovery of Function

• National University of Colombia

• Bidirectional communication
• Brain
• Exosomes
• Extracellular vesicles
• Microvesicles

• Animals
• Extracellular Vesicles/metabolism
• Brain
• Blood-Brain Barrier
• Biological Transport
• Cell Communication
• Exosomes/metabolism

• 81860225 National Natural Science Foundation of China

• Autism
• dentate gyrus
• hippocampus
• neurodevelopment
• neurogenesis
• stem cell

• Animals
• Autism Spectrum Disorder/therapy
• Hippocampus
• Neurons/physiology
• Neurogenesis/physiology

Retinal diseases are major causes of irreversible vision loss and blindness. Despite extensive research into their pathophysiology and etiology, pharmacotherapy effectiveness and surgical outcomes remain poor. Based largely on numerous preclinical studies, administration of mesenchymal stem cells (MSCs) as a therapeutic strategy for retinal diseases holds great promise, and various approaches have been applied to the therapies. However, hindered by the retinal barriers, the initial vision for the stem cell replacement strategy fails to achieve the anticipated effect and has now been questioned. Accumulating evidence now suggests that the paracrine effect may play a dominant role in MSC-based treatment, and MSC-derived extracellular vesicles emerge as a novel compelling alternative for cell-free therapy. This review summarizes the therapeutic potential and current strategies of this fascinating class of cells in retinal degeneration and other retinal dysfunctions.

• Humans
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells/physiology
• Extracellular Vesicles
• Retinal Diseases/therapy
• Cell- and Tissue-Based Therapy

The goal of this study is to see how combining physical activity with cell treatment impacts functional recovery in a stroke model. Molecular imaging and multimodal nanoparticles assisted in cell tracking and longitudinal monitoring (MNP). The viability of mesenchymal stem cell (MSC) was determined using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and bioluminescent image (BLI) after lentiviral transduction and MNP labeling. At random, the animals were divided into 5 groups (control-G1, and experimental G2-G5). The photothrombotic stroke induction was confirmed by local blood perfusion reduction and Triphenyltetrazolium chloride (TTC), and MSC in the G3 and G5 groups were implanted after 24 h, with BLI and near-infrared fluorescence image (NIRF) tracking these cells at 28 h, 2, 7, 14, and 28 days. During a 28-day period, the G5 also conducted physical training, whereas the G4 simply did the training. At 0, 7, 14, and 28 days, the animals were functionally tested using a cylinder test and a spontaneous motor activity test. MNP internalization in MSC was confirmed using brightfield and fluorescence microscopy. In relation to G1 group, only 3% of cell viability reduced. The G2–G5 groups showed more than 69% of blood perfusion reduction. The G5 group performed better over time, with a progressive recovery of symmetry and an increase of fast vertical movements. Up to 7 days, BLI and NIRF followed MSC at the damaged site, demonstrating a signal rise that could be connected to cell proliferation at the injury site during the acute phase of stroke. Local MSC therapy mixed with physical activity resulted in better results in alleviating motor dysfunction, particularly during the acute period. When it comes to neurorehabilitation, this alternative therapy could be a suitable fit.

• behavioral test
• bioluminescence
• cell therapy
• human bone marrow mesenchymal stem cells
• multimodal nanoparticles
• near-infrared fluorescence image
• physical exercise
• stroke

• Animals
• Cell- and Tissue-Based Therapy
• Exercise
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cells
• Stroke/therapy

Stroke is one of the major causes of disability and death worldwide. Some treatments for stroke exist, but existing treatment methods have limitations such as difficulty in the regeneration of damaged neuronal cells of the brain. Recently, mesenchymal stem cells (MSCs) have been studied as a therapeutic alternative for stroke, and various preclinical and case studies have been reported.

A 55-year-old man suffered an acute stroke, causing paralysis in the left upper and lower limbs. He intravenously transplanted the minimally manipulated human umbilical cord-derived MSCs (MM-UC-MSCs) twice with an 8-d interval. At 65 wk after transplantation, the patient returned to his previous occupation as a veterinarian with no adverse reactions.

MM-UC-MSCs transplantation potentially treats patients who suffer from acute ischemic stroke.

• Acute ischemic stroke
• Behavioral disorder
• Umbilical cord-derived mesenchymal stem cells
• Allogenic
• Cell therapy
• Minimal manipulation
• Case report

Overuse tendon injuries are a major cause of musculoskeletal morbidity in both human and equine athletes, due to the cumulative degenerative damage. These injuries present significant challenges as the healing process often results in the formation of inferior scar tissue. The poor success with conventional therapy supports the need to search for novel treatments to restore functionality and regenerate tissue as close to native tendon as possible. Mesenchymal stem cell (MSC)-based strategies represent promising therapeutic tools for tendon repair in both human and veterinary medicine. The translation of tissue engineering strategies from basic research findings, however, into clinical use has been hampered by the limited understanding of the multifaceted MSC mechanisms of action. In vitro models serve as important biological tools to study cell behavior, bypassing the confounding factors associated with in vivo experiments. Controllable and reproducible in vitro conditions should be provided to study the MSC healing mechanisms in tendon injuries. Unfortunately, no physiologically representative tendinopathy models exist to date. A major shortcoming of most currently available in vitro tendon models is the lack of extracellular tendon matrix and vascular supply. These models often make use of synthetic biomaterials, which do not reflect the natural tendon composition. Alternatively, decellularized tendon has been applied, but it is challenging to obtain reproducible results due to its variable composition, less efficient cell seeding approaches and lack of cell encapsulation and vascularization. The current review will overview pros and cons associated with the use of different biomaterials and technologies enabling scaffold production. In addition, the characteristics of the ideal, state-of-the-art tendinopathy model will be discussed. Briefly, a representative in vitro tendinopathy model should be vascularized and mimic the hierarchical structure of the tendon matrix with elongated cells being organized in a parallel fashion and subjected to uniaxial stretching. Incorporation of mechanical stimulation, preferably uniaxial stretching may be a key element in order to obtain appropriate matrix alignment and create a pathophysiological model. Together, a thorough discussion on the current status and future directions for tendon models will enhance fundamental MSC research, accelerating translation of MSC therapies for tendon injuries from bench to bedside.

• biomaterials
• bioreactors
• in vitro tendon models
• tendinopathy
• tendon

• adipose-derived mesenchymal stromal cell
• advanced therapy medicinal product
• pain
• regenerative medicine
• skin innervation
• wound healing

• Animals
• Burns/therapy
• Cell Plasticity
• Chronic Pain/therapy
• Cicatrix/therapy
• Clinical Trials as Topic
• Humans
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cells/physiology
• Quality of Life
• Regenerative Medicine/methods
• Tissue Engineering/methods
• Wound Healing

• Schwann cells
• angiogenesis
• exosomes
• nerve graft
• nerve regeneration
• peripheral nerve injury
• revascularization
• stem cell delivery
• stem cells
• vascularity

Oxidative stress associated with neuroinflammation is a key process involved in the pathophysiology of neurodegenerative diseases, and therefore, has been proposed as a crucial target for new therapies. Recently, the therapeutic potential of human adipose-derived stem cells (hASCs) has been investigated as a novel strategy for neuroprotection. These cells can be preconditioned by exposing them to mild stress in order to improve their response to oxidative stress. In this study, we evaluate the therapeutic potential of hASCs preconditioned with low doses of H₂O₂ (called HC016 cells) to overcome the deleterious effect of oxidative stress in an in vitro model of oligodendrocyte-like cells (HOGd), through two strategies: i, the culture of oxidized HOGd with HC016 cell-conditioned medium (CM), and ii, the indirect co-culture of oxidized HOGd with HC016 cells, which had or had not been exposed to oxidative stress. The results demonstrated that both strategies had reparative effects, oxidized HC016 cell co-culture being the one associated with the greatest recovery of the damaged HOGd, increasing their viability, reducing their intracellular reactive oxygen species levels and promoting their antioxidant capacity. Taken together, these findings support the view that HC016 cells, given their reparative capacity, might be considered an important breakthrough in cell-based therapies.

• H2O2 preconditioning
• antioxidant capacity
• cell therapy
• human adipose-derived stem cells
• oligodendrocyte-like cells
• oxidative stress

• cell therapy
• extracellular vesicles
• mesenchymal stromal cells
• neurodegenerative disorders
• polyglutamine disorders
• secretome

• Adipose tissue
• Animal model
• Canine
• Immunomodulation
• Inflammatory brain disease
• Mesenchymal stromal cell
• Multiple sclerosis
• Multipotent progenitor cell
• Placenta
• Translational research

• Animals
• Brain
• Brain Diseases
• Cell Proliferation
• Cells, Cultured
• Coculture Techniques
• Dogs
• Female
• Leukocytes, Mononuclear
• Mesenchymal Stem Cells
• Placenta
• Pregnancy
• Vascular Endothelial Growth Factor A

• R01 NS100761 NINDS NIH HHS
• Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (BR)
• National Institutes of Health
• Shriners Hospitals for Children
• School of Veterinary Medicine, University of California, Davis
• National Center for Advancing Translational Sciences

The regenerative capability of the central nervous system is limited after traumatic spinal cord injury (SCI) due to intrinsic and extrinsic factors that inhibit spinal cord regeneration, resulting in deficient functional recovery. It has been shown that strategies, such as pre-degenerated peripheral nerve (PPN) grafts or the use of bone marrow stromal cells (BMSCs) or exogenous molecules, such as chondroitinase ABC (ChABC) promote axonal growth and remyelination, resulting in an improvement in locomotor function. These treatments have been primarily assessed in acute injury models. The aim of the present study is to evaluate the ability of several single and combined treatments in order to modify the course of chronic complete SCI in rats. A complete cord transection was performed at the T9 level. One month later, animals were divided into five groups: original injury only (control group), and original injury plus spinal cord re-transection to create a gap to accommodate BMSCs, PPN, PPN + BMSCs, and PPN + BMSCs + ChABC. In comparison with control and single-treatment groups (PPN and BMSCs), combined treatment groups (PPN + BMSCs and PPN + BMSCs + ChABC) showed significative axonal regrowth, as revealed by an increase in GAP-43 and MAP-1B expression in axonal fibers, which correlated with an improvement in locomotor function. In conclusion, the combined therapies tested here improve locomotor function by enhancing axonal regeneration in rats with chronic SCI. Further studies are warranted to refine this promising line of research for clinical purposes.

• BBB modified score
• axonal regeneration
• bone marrow stromal cell transplant
• functional recovery
• kinematic analysis
• pre-degeneration peripheral nerve transplant

Mesenchymal stem cells (MSCs) are among the most frequently used cell type for regenerative medicine. A large number of studies have shown the beneficial effects of MSC-based therapies to treat different pathologies, including neurological disorders, cardiac ischemia, diabetes, and bone and cartilage diseases. However, the therapeutic potential of MSCs in cancer is still controversial. While some studies indicate that MSCs may contribute to cancer pathogenesis, emerging data reported the suppressive effects of MSCs on cancer cells. Because of this reality, a sustained effort to understand when MSCs promote or suppress tumor development is needed before planning a MSC-based therapy for cancer. Herein, we provide an overview on the therapeutic application of MSCs for regenerative medicine and the processes that orchestrates tissue repair, with a special emphasis placed on cancer, including central nervous system tumors. Furthermore, we will discuss the current evidence regarding the double-edged sword of MSCs in oncological treatment and the latest advances in MSC-based anti-cancer agent delivery systems.

• anti-tumor activity
• cancer
• cell therapy
• mesenchymal stem cells
• therapeutic agents

• Cell-based therapy
• Clinical trials
• Mesenchymal stem cells
• Nervous system disorders
• Neuronal differentiation

• Cell therapy
• Neurodegenerative disease
• Neuroprotection
• Oxidative damage
• Stem cells

Immune cell trafficking into the CNS is considered to contribute to pathogenesis in MS and its animal model, EAE. Disruption of the blood–brain barrier (BBB) is a hallmark of these pathologies and a potential target of therapeutics. Human embryonic stem cell-derived mesenchymal stem/stromal cells (hES-MSCs) have shown superior therapeutic efficacy, compared to bone marrow-derived MSCs, in reducing clinical symptoms and neuropathology of EAE. However, it has not yet been reported whether hES-MSCs inhibit and/or repair the BBB damage associated with neuroinflammation that accompanies EAE.

BMECs were cultured on Transwell inserts as a BBB model for all the experiments. Disruption of BBB models was induced by TNF-α, a pro-inflammatory cytokine that is a hallmark of acute and chronic neuroinflammation.

Results indicated that hES-MSCs reversed the TNF-α-induced changes in tight junction proteins, permeability, transendothelial electrical resistance, and expression of adhesion molecules, especially when these cells were placed in direct contact with BMEC.

hES-MSCs and/or products derived from them could potentially serve as novel therapeutics to repair BBB disturbances in MS.

The online version of this article (10.1186/s12987-019-0138-5) contains supplementary material, which is available to authorized users.

• Blood brain barrier
• Brain endothelial cells
• MS and EAE
• Mesenchymal stem/stromal cells
• Tight junction

The main treatment available for idiopathic macular holes is represented by pars plana vitrectomy with internal limiting membrane peeling. However, late-stage macular holes are affected by a higher risk of surgical failure. Although adjuvant techniques can be employed, a satisfactory functional recovery is difficult to achieve in refractory macular holes. Given their neuroprotective and antiapoptotic properties, mesenchymal stem cells (MSCs) may represent an appealing approach to treat these extreme cases. The purpose of this review is to highlight the findings regarding healing mechanisms exerted by mesenchymal stem cells and preliminary application in cases of refractory macular holes. When compared with MSCs, MSC-derived exosomes may represent a feasible alternative, given their reduced risk of undesired proliferation and easiness of use.

• IKVAV
• human mesenchymal stem cell
• neurons
• peptide amphiphile
• transdifferentiation

• Bone Marrow Cells
• Cell Transdifferentiation/drug effects
• Humans
• Laminin/chemistry
• Laminin/pharmacology
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/metabolism
• Nanofibers/chemistry
• Neurons/cytology
• Neurons/metabolism
• Peptide Fragments/chemistry
• Peptide Fragments/pharmacology

• ischemic stroke
• stem cell types
• stem cells
• treatment

Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have been shown to prevent brain damage and improve neurocognition following intraventricular hemorrhage (IVH). However, the molecular mechanisms underlying the effects of hUCB-MSCs are still elusive. Thus, as the hippocampus is essential for learning, memory, and cognitive functions and is intimately involved in the ventricular system, making it a potential site of IVH-induced injury, we determined the molecular basis of the effects of hUCB-derived MSCs on hippocampal neurogenesis and the recovery of hippocampal neural circuits after IVH in a rodent model.

We inflicted severe IVH injury on postnatal day 4 (P4) in rats. After confirmation of successful induction of IVH using MRI (P5), intracerebroventricular administration of MSCs (ICV-MSC) was performed at 2 days post-injury (P6). For hippocampal synaptic determination, a rat entorhinal-hippocampus (EH) organotypic slice co-culture (OSC) was performed using day 3 post-IVH brains (P7) with or without ICV-MSCs. A similar strategy of experiments was applied to those rats receiving hUCB-MSC transfected with BDNF-Si-RNA for knockdown of BDNF or scrambled siRNA controls after IVH. The molecular mechanism of the MSCs effects on neurogenesis and the attenuation of neuron death was determined by evaluation of BDNF-TrkB-Akt-CREB signaling axis.

We showed that treatment with hUCB-MSCs attenuated neuronal loss and promoted neurogenesis in the hippocampus, an area highly vulnerable to IVH-induced brain injury. hUCB-MSCs activate BDNF-TrkB receptor signaling, eliciting intracellular activation of Akt and/or Erk and subsequent phosphorylation of CREB, which is responsible for promoting rat BDNF transcription. In addition to the beneficial effects of neuroprotection and neurogenesis, hUCB-MSCs also contribute to the restoration of impaired synaptic circuits in the hippocampus and improve neurocognitive functions in IVH-injured neonatal rat through BDNF-TrkB-CREB signaling axis activation.

Our data suggest that hUCB-MSCs possess therapeutic potential for treating neuronal loss and neurocognitive dysfunction in IVH through the activation of intracellular TrkB-CREB signaling that is invoked by hUCB-MSC-secreted BDNF.

The online version of this article (10.1186/s13287-018-1052-5) contains supplementary material, which is available to authorized users.

• BDNF
• CREB
• Hippocampus
• Intraventricular hemorrhage
• Mesenchymal stem cells

• Cerebral ischemia
• Human bone marrow–derived mesenchymal stem cell
• Minocycline

• Exosomes
• Macular hole
• Mesenchymal stem cells
• Pars plana vitrectomy

• Aged
• Cataract Extraction
• Endotamponade
• Exosomes/transplantation
• Female
• Flow Cytometry
• Fluorocarbons/administration & dosage
• Follow-Up Studies
• Humans
• Intravitreal Injections
• Male
• Mesenchymal Stem Cell Transplantation
• Middle Aged
• Pilot Projects
• Retinal Perforations/diagnostic imaging
• Retinal Perforations/physiopathology
• Retinal Perforations/therapy
• Retrospective Studies
• Silicone Oils/administration & dosage
• Tomography, Optical Coherence
• Visual Acuity/physiology
• Vitrectomy
• Wound Healing/physiology

• 81371005 National Natural Science Foundation of China
• 15JCZDJC35600 Tianjin Municipal Science and Technology Commission

Stroke induces complex and dynamic, local and systemic changes including inflammatory reactions, immune responses, and repair and recovery processes. Mesenchymal stem cells (MSCs) have been shown to enhance neurological recovery after stroke. We hypothesized that serum factors play a critical role in the activation of bone marrow (BM) MSCs after stroke such as by increasing proliferation, paracrine effects, and rejuvenation. Human MSCs (hMSCs) were grown in fetal bovine serum (FBS), normal healthy control serum (NS), or stroke patient serum (SS). MSCs cultured in growth medium with 10% SS or NS exhibited higher proliferation indices than those cultured with FBS (P < 0.01). FBS-, NS-, and SS-hMSCs showed differences in the expression of trophic factors; vascular endothelial growth factor, glial cell–derived neurotrophic factor, and fibroblast growth factor were densely expressed in samples cultured with SS (P < 0.01). In addition, SS-MSCs revealed different cell cycle– or aging-associated messenger RNA expression in a later passage, and β-galactosidase staining showed the senescence of MSCs observed during culture expansion was lower in MSCs cultured with SS than those cultured with NS or FBS (P < 0.01). Several proteins related to the activity of receptors, growth factors, and cytokines were more prevalent in the serum of stroke patients than in that of normal subjects. Neurogenesis and angiogenesis were markedly increased in rats that had received SS-MSCs (P < 0.05), and these rats showed significant behavioral improvements (P < 0.01). Our results indicate that stroke induces a process of recovery via the activation of MSCs. Culture methods for MSCs using SS obtained during the acute phase of a stroke could constitute a novel MSC activation method that is feasible and efficient for the neurorestoration of stroke.

• mesenchymal stem cells
• stem cell activation
• stroke

Adult neurogenesis involves persistent proliferative neuroprogenitor populations that reside within distinct regions of the brain. This phenomenon was first described over 50 years ago and it is now firmly established that new neurons are continually generated in distinct regions of the adult brain. The potential of enhancing the neurogenic process lies in improved brain cognition and neuronal plasticity particularly in the context of neuronal injury and neurodegenerative disorders. In addition, adult neurogenesis might also play a role in mood and affective disorders. The factors that regulate adult neurogenesis have been broadly studied. However, the underlying molecular mechanisms of regulating neurogenesis are still not fully defined. In this review, we will provide critical analysis of our current understanding of the factors and molecular mechanisms that determine neurogenesis. We will further discuss pre-clinical and clinical studies that have investigated the potential of modulating neurogenesis as therapeutic intervention in neurodegeneration.

• Cytokines
• Extrinsic factors
• Neurotrophins
• Niche
• Stem cells
• Therapy
• Transcription factors

Bone marrow mesenchymal stem cells (BM-MSCs) elicit neuroprotective effects, and their repair ability has been investigated in different experimental models. We aimed to investigate the effect of multiple i.p. BM-MSCs injections in the cuprizone model of multiple sclerosis in mice.

Adult male C57BL/6 mice (n = 40) were fed a regular diet or a diet containing cuprizone (0.2% w/w) for six weeks. Bone marrow samples were taken from patients with spinal cord injury. BM-MSCs (2 × 10⁶ in 1 milliliter medium) were administered intraperitoneally for two consecutive weeks at the end of the forth weeks of cuprizone administration. Animals (n = 12) were perfused with 10% paraformaldehyde at the end of sixth week. The brains were sectioned coronally in 6-8-μm thickness (-2.3 to 1.8 mm from bregma). The sections were stained by luxol fast blue-cresyl violet, and images were captured via a microscope. Demyelination ratio was estimated in corpus callosum in a blind manner. A quantitative real-time PCR was used to measure the myelin basic protein gene expression at sixth week.

Histologically, cuprizone induced demyelination in the corpus callosum. Demyelinated area was diminished in the corpus callosum of cell-administered group. Cuprizone could decrease myelin-binding protein mRNAs expression in corpus callosum, which was significantly recovered after BM-MSCs injections.

Our data indicated a remyelination potency of multiple i.p. BM-MSCs in the cuprizone model of multiple sclerosis in mice.

• Cuprizone
• Mesenchymal stem cells
• Mice
• Multiple sclerosis

• Alzheimer's disease
• Human umbilical cord-derived mesenchymal stem cells
• Resveratrol, SIRT1
• Transgenic mice

• Immunomodulation
• Mesenchymal stem cells
• Neurodegenerative diseases
• Neurogenesis
• Neurotrophic factors

• Gerotarget
• behavioural disorders
• doublecortin (DCX)
• hippocampal neurogenesis
• mesenchymal stem cells (MSC)
• valproic acid (VPA)

• Animals
• Cell Differentiation/physiology
• Disease Models, Animal
• Doublecortin Protein
• Female
• GABA Agents/toxicity
• Hippocampus
• Immunohistochemistry
• Maze Learning
• Mesenchymal Stem Cell Transplantation/methods
• Mice
• Neurodevelopmental Disorders/chemically induced
• Neurodevelopmental Disorders/complications
• Neurogenesis/physiology
• Neurons/cytology
• Pregnancy
• Prenatal Exposure Delayed Effects/etiology
• Prenatal Exposure Delayed Effects/therapy
• Social Behavior
• Valproic Acid/toxicity

The dental follicle is an ectomesenchymal tissue surrounding the developing tooth germ. Human dental follicle cells (hDFCs) have the capacity to commit to differentiation into multiple cell types. Here we investigated the capacity of hDFCs to differentiate into neural cells and the efficiency of a two-step strategy involving floating neurosphere-like bodies for neural differentiation. Undifferentiated hDFCs showed a spindle-like morphology and were positive for neural markers such as nestin, β-III-tubulin, and S100β. The cellular morphology of several cells was neuronal-like including branched dendrite-like processes and neurites. Next, hDFCs were used for neurosphere formation in serum-free medium containing basic fibroblast growth factor, epidermal growth factor, and B27 supplement. The number of cells with neuronal-like morphology and that were strongly positive for neural markers increased with sphere formation. Gene expression of neural markers also increased in hDFCs with sphere formation. Next, gene expression of neural markers was examined in hDFCs during neuronal differentiation after sphere formation. Expression of Musashi-1 and Musashi-2, MAP2, GFAP, MBP, and SOX10 was upregulated in hDFCs undergoing neuronal differentiation via neurospheres, whereas expression of nestin and β-III-tubulin was downregulated. In conclusion, hDFCs may be another optimal source of neural/glial cells for cell-based therapies to treat neurological diseases.

• peripheral nerve
• regeneration
• stem cells
• transplantation

• Animals
• Cell Differentiation
• Cell- and Tissue-Based Therapy/methods
• Cell- and Tissue-Based Therapy/trends
• Humans
• Nerve Regeneration
• Peripheral Nerve Injuries/physiopathology
• Peripheral Nerve Injuries/therapy
• Peripheral Nerves/pathology
• Peripheral Nerves/physiopathology
• Schwann Cells/cytology
• Stem Cell Transplantation/methods
• Stem Cells/classification
• Stem Cells/cytology

• R01 HL118084 NHLBI NIH HHS

• electroretinogram
• mesenchymal stem cells
• optical coherence tomography
• recurrent experimental autoimmune uveitis

• Arthritis
• Endothelial cells
• Endothelial cell–mesenchymal stem cell interactions
• Extracellular vesicles
• Mesenchymal stem cells
• Muscle-derived stem cells
• Neurotrophic activity

• Adult Stem Cells/physiology
• Animals
• Cell- and Tissue-Based Therapy/methods
• Humans
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cells/physiology
• Musculoskeletal Diseases/therapy
• Regeneration/physiology
• Vascular Diseases/therapy

• U18 TR000532 NCATS NIH HHS
• T32 EB001026 NIBIB NIH HHS
• Commonwealth of Pennsylvania Department of Health
• National Institutes of Health
• U.S. Department of Defense

Bone marrow and umbilical cord stromal cells are multipotential stem cells that have the ability to produce growth factors that play an important role in survival and generation of axons. The goal of this study was to evaluate the effects of the two different mesenchymal stem cells on peripheral nerve regeneration.

In this experimental study, a 10 mm segment of the left sciatic nerve of male Wistar rats (250-300 g) was removed with a silicone tube interposed into this nerve gap. Bone marrow stromal cells (BMSCs) and human umbilical cord stromal cells (HUCSCs) were respectively obtained from rat and human. The cells were sepa- rately cultured and transplanted into the nerve gap. The sciatic nerve regeneration was evaluated by immunohistochemistry, and light and electron microscopy. Moreover, histo- morphology of the gastrocnemius muscle was observed.

The nerve regeneration in the BMSCs and HUCSCs groups that had received the stem cells was significantly more favorable than the control group. In addition, the BM- SCs group was significantly more favorable than the HUCSCs group (P<0.05).

The results of this study suggest that both homograft BMSCs and het- erograft HUCSCs may have the potential to regenerate peripheral nerve injury and transplantation of BMSCs may be more effective than HUCSCs in rat.

• Bone Marrow Stromal Cells
• Human Umbilical Cord Stromal Cells
• Peripheral Nerve
• Regeneration
• Trans- plantation

Mesenchymal stem cells are posing as a promising character in the most recent therapeutic strategies and, since their discovery, extensive knowledge on their features and functions has been gained. In recent years, innovative sources have been disclosed in alternative to the bone marrow, conveying their associated ethical concerns and ease of harvest, such as the umbilical cord tissue and the dental pulp. These are also amenable of cryopreservation and thawing for desired purposes, in benefit of the donor itself or other patients in pressing need. These sources present promising possibilities in becoming useful cell sources for therapeutic applications in the forthcoming years. Effective and potential applications of these cellular-based strategies for the regeneration of peripheral nerve are overviewed, documenting recent advances and identified issues for this research area in the near future. Finally, besides the differentiation capacities attributed to mesenchymal stem cells, advances in the recognition of their effective mode of action in the regenerative theatre have led to a new area of interest: the mesenchymal stem cells' secretome. The paracrine modulatory pathway appears to be a major mechanism by which these are beneficial to nerve regeneration and comprehension on the specific growth factors, cytokine, and extracellular molecules secretion profiles is therefore of great interest.