• central nervous system
• central peripheral target organ
• multilevel pathological analysis
• nerve regeneration
• peripheral nerve injury
• peripheral nervous system
• target organs
• therapeutic approach

Spinal cord injury (SCI) is a devastating condition with complex pathological mechanisms that lead to sensory, motor, and autonomic dysfunction below the site of injury. To date, no effective therapy is available for the treatment of SCI. Recently, bone marrow-derived mesenchymal stem cells (BMMSCs) have been considered to be the most promising source for cellular therapies following SCI. The objective of the present review is to summarize the most recent insights into the cellular and molecular mechanism using BMMSC therapy to treat SCI. In this work, we review the specific mechanism of BMMSCs in SCI repair mainly from the following aspects: Neuroprotection, axon sprouting and/or regeneration, myelin regeneration, inhibitory microenvironments, glial scar formation, immunomodulation, and angiogenesis. Additionally, we summarize the latest evidence on the application of BMMSCs in clinical trials and further discuss the challenges and future directions for stem cell therapy in SCI models.

• Spinal cord injury
• Bone marrow derived mesenchymal stem cells
• Neuroprotection
• Axon
• Myelin
• Inhibitory microenvironment

• Bone pain
• Epidermal growth factor receptor (EGFR/ErbB2) signaling
• Extracellular vesicles
• Neuronal electrophysiology
• Osteoclast secretome
• Sensory neurons sprouting

Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration.

3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL + MSCs (NGC multi-functionalized with 10⁶ canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75^NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve.

The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75^NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair.

3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.

• 3D printing
• Canine mesenchymal stem cells
• Cell-based therapy
• Fibrin
• Nerve guidance conduits
• Nerve regeneration
• Scaffold
• Sciatic nerve injury
• Tissue engineering

• Bone
• Homeostasis
• Neurophysiology

• SFRH/BD/128771/2017 Ministry of Education and Science | Fundação para a Ciência e a Tecnologia (Portuguese Science and Technology Foundation)

• Animal model of alcoholism
• basic fibroblast growth factor intervention
• bone marrow mesenchymal stem cell intervention
• mechanical property
• sciatic nerve injury

• Dorsal root ganglion
• Neural repair
• Neural tissue-committed stem cells
• Sensory neurons
• Transplantation

• Action Potentials
• Animals
• Behavior, Animal
• Cell Separation
• Cell Shape
• Cell Survival
• Disease Models, Animal
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells/cytology
• Nerve Regeneration
• Nerve Tissue/cytology
• Nerve Tissue Proteins/metabolism
• Neural Conduction
• Neurons/cytology
• Peripheral Nerve Injuries/pathology
• Peripheral Nerve Injuries/physiopathology
• Peripheral Nerve Injuries/therapy
• Rats, Sprague-Dawley
• Sensory Receptor Cells/cytology
• Sensory Receptor Cells/transplantation
• Spheroids, Cellular/cytology

• ZR2014HM009 Shandong Provincial Natural Science Foundation
• BS2015SW021 Shandong Provincial Natural Science Foundation
• 2014GSF118177 Natural Science Foundation of Shandong Province (CN)
• ZR2017MC052 Natural Science Foundation of Shandong Province (CN)
• 81271717 Natural Science Foundation of Jilin Province (CN)
• 81571821 Natural Science Foundation of China
• AWS14C001 The army subject funds of China
• 13CXZ028 The army subject funds of China

Peripheral nerve injury requires optimal conditions in both macro-environment and microenvironment for promotion of axonal regeneration. However, most repair strategies of traumatic peripheral nerve injury often lead to dissatisfying results in clinical outcome. Though various strategies have been carried out to improve the macro-environment, the underlying molecular mechanism of axon regeneration in the microenvironment provided by nerve conduit remains unclear. In this study, we evaluate the effects of from adipose-derived mesenchymal stem cells (adMSCs) originating exosomes with respect to sciatic nerve regeneration and neurite growth. Molecular and immunohistochemical techniques were used to investigate the presence of characteristic exosome markers. A co-culture system was established to determine the effect of exosomes on neurite elongation in vitro. The in vivo walking behaviour of rats was evaluated by footprint analysis, and the nerve regeneration was assessed by immunocytochemistry. adMSCs secrete nano-vesicles known as exosomes, which increase neurite outgrowth in vitro and enhance regeneration after sciatic nerve injury in vivo. Furthermore, we showed the presence of neural growth factors transcripts in adMSC exosomes for the first time. Our results demonstrate that exosomes, constitutively produced by adMSCs, are involved in peripheral nerve regeneration and have the potential to be utilised as a therapeutic tool for effective tissue-engineered nerves.

• Axons regeneration
• Microvesicles
• Neurites stimulation
• adMSCs

• Brain-derived neurotrophic factor
• Clinical trials
• Genetic modification
• Mesenchymal stem cells
• Neuroprotection
• Neuroregeneration
• Peripheral nerve regeneration
• Schwann cells
• Transdifferentiation
• Transplantation

• Bone marrow transplantation
• Caspase-3
• Mesenchymal stromal cells
• Mice
• Spinal cord injuries

Mesenchymal stem cells (MSCs) have been used for cell-based therapies in regenerative medicine, with increasing importance in central and peripheral nervous system repair. However, MSCs grafting present disadvantages, such as, a high number of cells required for transplantation and low survival rate when transplanted into the central nervous system (CNS). In line with this, MSCs secretome which present on its composition a wide range of molecules (neurotrophins, cytokines) and microvesicles, can be a solution to surpass these problems. However, the effect of MSCs secretome in axonal elongation is poorly understood. In this study, we demonstrate that application of MSCs secretome to both rat cortical and hippocampal neurons induces an increase in axonal length. In addition, we show that this growth effect is axonal intrinsic with no contribution from the cell body. To further understand which are the molecules required for secretome-induced axonal outgrowth effect, we depleted brain-derived neurotrophic factor (BDNF) from the secretome. Our results show that in the absence of BDNF, secretome-induced axonal elongation effect is lost and that axons present a reduced axonal growth rate. Altogether, our results demonstrate that MSCs secretome is able to promote axonal outgrowth in CNS neurons and this effect is mediated by BDNF.

Ciliary neurotrophic factor has neuroprotective effects mediated through signal transducer and Janus kinase (JAK) 2/activator of transcription 3 (STAT3) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. Whether ciliary neurotrophic factor is neuroprotective for glutamate-induced excitotoxicity of dorsal root ganglion neurons is poorly understood. In the present study, the in vitro neuroprotective effects of ciliary neurotrophic factor against glutamate-induced excitotoxicity were determined in a primary culture of dorsal root ganglion neurons from Wistar rat embryos at embryonic day 15. Whether the JAK2/STAT3 and PI3K/Akt signaling pathways were related to the protective effects of ciliary neurotrophic factor was also determined. Glutamate exposure inhibited neurite outgrowth, cell viability, and growth-associated protein 43 expression and promoted apoptotic neuronal cell death, all of which were reversed by the administration of exogenous ciliary neurotrophic factor. Additionally, preincubation with either JAK2 inhibitor AG490 or PI3K inhibitor LY294002 blocked the neuroprotective effect of ciliary neurotrophic factor. These data indicate that the two pathways JAK2/STAT3 and PI3K/Akt play major roles in mediating the in vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity.

• JAK2/STAT3
• PI3K/Akt
• ciliary neurotrophic factor
• dorsal root ganglion
• excitotoxicity
• glutamate
• growth-associated protein 43
• nerve regeneration
• neural regeneration
• neurite outgrowth
• neuron
• neuroprotection

Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein while maintaining rectal temperature at 34 ± 0.5°C for 6 hours (mild hypothermia). Hematoxylin-eosin staining showed that astrocytes gathered around the injury site and formed scars at 4 weeks post-transplantation. Compared with rats transplanted with bone marrow stem cells under normal temperature, rats transplanted with bone marrow stem cells under hypothermia showed increased numbers of proliferating cells (bromodeoxyuridine-positive cells), better recovery of somatosensory-evoked and motor-evoked potentials, greater Basso, Beattie, and Bresnahan locomotor rating scores, and an increased degree of angle in the incline plate test. These findings suggested that hypothermia combined with bone marrow mesenchymal stem cells transplantation effectively promoted electrical conduction and nerve functional repair in a rat model of spinal cord hemisection injury.

• bone marrow mesenchymal stem cells
• electrophysiological function
• hypothermia
• spinal cord hemisection injury
• transplantation

Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the peripheral nervous system, neurogenesis is thought to be active only during prenatal development, with the exception of the olfactory neuroepithelium. However, sensory ganglia in the adult peripheral nervous system have been reported to contain precursor cells that can proliferate in vitro and be induced to differentiate into neurons. The occurrence of insult-induced neurogenesis, which has been reported by several investigators in the brain, is limited to a few recent reports for the peripheral nervous system. These reports suggest that damage to the adult nervous system induces mechanisms similar to those that control the generation of new neurons during prenatal development. Understanding conditions under which neurogenesis can be induced in physiologically non-neurogenic regions in adults is one of the major challenges for developing therapeutic strategies to repair neurological damage. However, the induced neurogenesis in the peripheral nervous system is still largely unexplored. This review presents the history of research on adult neurogenesis in the peripheral nervous system, which dates back more than 100 years and reveals the evidence on the under estimated potential for generation of new neurons in the adult peripheral nervous system.

• adult neurogenesis
• autonomic ganglia
• dorsal root ganglia
• mammals
• peripheral nervous system
• stem cells

The microenvironment of the injured spinal cord is hypothesized to be involved in driving the differentiation and survival of engrafted neural stem cells (NSCs). Hypothermia is known to improve the microenvironment of the injured spinal cord in a number of ways. To investigate the effect of NSC transplantation in combination with hypothermia on the recovery of rat spinal cord injury, 60 Sprague-Dawley female rats were used to establish a spinal cord hemisection model. They were divided randomly into three groups: A, spinal cord injury group; B, NSC transplantation group; and C, NSC transplantation + hypothermia group. At 1, 2, 4, 6 and 8 weeks post-injury, the motor function of all animals was evaluated using the Basso, Beattie and Besnaham locomotor scoring system and the inclined plane test. At 4 weeks post-transplantation, histological analysis and immunocytochemistry were performed. At 8 weeks post-transplantation, horseradish peroxidase nerve tracing and transmission electron microscopy were conducted to observe axonal regeneration. The outcome of hind limb motor function recovery in group C significantly surpassed that in group B at 4 weeks post-injury (P<0.05). Recovery was also observed in group A, but to a lesser degree. For the pathological sections no neural axonal were observed in group A. A few axon-like structures were observed in group B and more in group C. Horseradish peroxidase-labeled neurofibers and bromodeoxyuridine-positive cells were observed in the spinal cords of group C. Fewer of these cells were found in group B and fewer still in group A. The differences among the three groups were significant (P<0.05). Using transmission electron microscopy, newly formed nerve fibers and myelinated nerve fibers were observed in the central transverse plane in groups B and C, although these nerve fibers were not evident in group A. In conclusion, NSC transplantation promoted the recovery of hind limb function in rats, and combination treatment with hypothermia produced synergistic effects.

• NSFC grant
• bone marrow mesenchymal stem cells
• cell transplantation
• microtubule-associated protein 1B
• nerve regeneration
• neural regeneration
• phosphorylation
• protein phosphatase 2A
• signal transduction
• spinal cord injury

We studied the morphology and the cortical representation of the median nerve (MN), 10 weeks after a transection immediately followed by treatment with tubulization using a polycaprolactone (PCL) conduit with or without bone marrow-derived mesenchymal stem cell (MSC) transplant. In order to characterize the cutaneous representation of MN inputs in primary somatosensory cortex (S1), electrophysiological cortical mapping of the somatosensory representation of the forepaw and adjacent body parts was performed after acute lesion of all brachial plexus nerves, except for the MN. This was performed in ten adult male Wistar rats randomly assigned in three groups: MN Intact (n = 4), PCL-Only (n = 3), and PCL+MSC (n = 3). Ten weeks before mapping procedures in animals from PCL-Only and PCL+MSC groups, animal were subjected to MN transection with removal of a 4-mm-long segment, immediately followed by suturing a PCL conduit to the nerve stumps with (PCL+MSC group) or without (PCL-Only group) injection of MSC into the conduit. After mapping the representation of the MN in S1, animals had a segment of the regenerated nerve processed for light and transmission electron microscopy. For histomorphometric analysis of the nerve segment, sample size was increased to five animals per experimental group. The PCL+MSC group presented a higher number of myelinated fibers and a larger cortical representation of MN inputs in S1 (3,383 ± 390 fibers; 2.3 mm², respectively) than the PCL-Only group (2,226 ± 575 fibers; 1.6 mm²). In conclusion, MSC-based therapy associated with PCL conduits can improve MN regeneration. This treatment seems to rescue the nerve representation in S1, thus minimizing the stabilization of new representations of adjacent body parts in regions previously responsive to the MN.

• cortical plasticity
• median nerve lesion
• nerve regeneration
• polycaprolactone conduits
• rat
• stem-cell therapy

The goal of this study was to determine and compare the effects of the secretome of mesenchymal stem cells (MSCs) isolated from human bone-marrow (BMSCs) and the Wharton jelly surrounding the vein and arteries of the umbilical cord (human umbilical cord perivascular cells (HUCPVCs)) on the survival and differentiation of a human neuroblastoma cell line (SH-SY5Y). For this purpose, SH-SY5Y cells were differentiated with conditioned media (CM) from the MSCs populations referred above. Retinoic acid cultured cells were used as control for neuronal differentiated SH-SY5Y cells. SH-SY5Y cells viability assessment revealed that the secretome of BMSCs and HUCPVCs, in the form of CM, was able to induce their survival. Moreover, immunocytochemical experiments showed that CM from both MSCs was capable of inducing neuronal differentiation of SH-SY5Y cells. Finally, neurite lengths assessment and quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) analysis demonstrated that CM from BMSCs and HUCPVCs differently induced neurite outgrowth and mRNA levels of neuronal markers exhibited by SH-SY5Y cells. Overall, our results show that the secretome of both BMSCs and HUCPVCs was capable of supporting SH-SY5Y cells survival and promoting their differentiation towards a neuronal phenotype.

• mesenchymal stromal cells
• neuroprotection
• paracrine

• Bone marrow mesenchymal stem cells
• Cell-based therapy
• Mechanisms
• Nerve regeneration
• Therapeutic strategies

• Clinical trials
• Mesenchymal stem cells
• Neurotrauma
• Pre-clinical studies
• Stem cell therapy

Administration of mesenchymal stromal cells (MSC) improves functional outcome in the SOD1G93A mouse model of the degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS) as well as in models of other neurological disorders. We have now investigated the effect of the interaction between MSC and motor neurons (derived from both non-transgenic and mutant SOD1G93A transgenic mice), NSC-34 cells and glial cells (astrocytes, microglia) (derived again from both non-transgenic and mutant SOD1G93A ALS transgenic mice) in vitro. In primary motor neurons, NSC-34 cells and astrocytes, MSC conditioned medium (MSC CM) attenuated staurosporine (STS) - induced apoptosis in a concentration-dependent manner. Studying MSC CM-induced expression of neurotrophic factors in astrocytes and NSC-34 cells, we found that glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) gene expression in astrocytes were significantly enhanced by MSC CM, with differential responses of non-transgenic and mutant astrocytes. Expression of Vascular Endothelial Growth Factor (VEGF) in NSC-34 cells was significantly upregulated upon MSC CM-treatment. MSC CM significantly reduced the expression of the cytokines TNFα and IL-6 and iNOS both in transgenic and non-transgenic astrocytes. Gene expression of the neuroprotective chemokine Fractalkine (CX3CL1) was also upregulated in mutant SOD1G93A transgenic astrocytes by MSC CM treatment. Correspondingly, MSC CM increased the respective receptor, CX3CR1, in mutant SOD1G93A transgenic microglia. Our data demonstrate that MSC modulate motor neuronal and glial response to apoptosis and inflammation. MSC therefore represent an interesting candidate for further preclinical and clinical evaluation in ALS.

• Amyotrophic Lateral Sclerosis/genetics
• Amyotrophic Lateral Sclerosis/metabolism
• Animals
• Apoptosis/drug effects
• Astrocytes/drug effects
• Astrocytes/metabolism
• Cells, Cultured
• Chemokine CX3CL1/metabolism
• Ciliary Neurotrophic Factor/metabolism
• Culture Media, Conditioned/pharmacology
• Glial Cell Line-Derived Neurotrophic Factors/metabolism
• Humans
• Mesenchymal Stem Cells/drug effects
• Mesenchymal Stem Cells/metabolism
• Mice
• Microglia/drug effects
• Microglia/metabolism
• Motor Neurons/drug effects
• Motor Neurons/metabolism
• Staurosporine/pharmacology

It has been demonstrated that the infusion of bone marrow stromal cells (BMSCs) through the cerebrospinal fluid (CSF) has beneficial effects on acute spinal cord injury (SCI) in rats. The present study examined whether BMSC infusion into the CSF is effective for subacute (1- and 2-week post-injury), and/or chronic (4-week post-injury) SCI in rats. The spinal cord was contused by dropping a weight at the thoracic 8-9 levels. BMSCs cultured from GFP-transgenic rats of the same strain were injected three times (once weekly) into the CSF through the fourth ventricle, beginning at 1, 2 and 4 weeks post-injury. At 4 weeks after initial injection, the average BBB score for locomotor assessment increased from 1.0–3.5 points before injection to 9.0-10.9 points in the BMSC-injection subgroups, while, in the PBS (vehicle)-injection subgroups, it increased only from 0.5–4.0 points before injection to 3.0-5.1 points. Numerous axons associated with Schwann cells extended longitudinally through the connective tissue matrices in the astrocyte-devoid lesion without being blocked at either the rostral or the caudal borders in the BMSC-injection subgroups. A small number of BMSCs were found to survive within the spinal cord lesion in SCI of the 1-week post-injury at 2 days of injection, but none at 7 days. No BMSCs were found in the spinal cord lesion at 2 days or at 7 days in the SCI of the 2-week and the 4-week post-injury groups. In an in vitro experiment, BMSC-injected CSF promoted the survival and the neurite extension of cultured neurons more effectively than did the PBS-injected CSF. These results indicate that BMSCs had beneficial effects on locomotor improvement as well as on axonal regeneration in both subacute and chronic SCI rats, and the results also suggest that BMSCs might function as neurotrophic sources via the CSF.

• Animals
• Bone Marrow Transplantation/methods
• Female
• Locomotion
• Neurons/pathology
• Rats
• Rats, Sprague-Dawley
• Rats, Transgenic
• Spinal Cord Injuries/cerebrospinal fluid
• Spinal Cord Injuries/pathology
• Spinal Cord Injuries/physiopathology
• Spinal Cord Injuries/surgery
• Stromal Cells/transplantation

• Analysis of Variance
• Animals
• Animals, Newborn
• Cells, Cultured
• Coculture Techniques
• Culture Media, Conditioned/pharmacology
• Enzyme-Linked Immunosorbent Assay
• Intercellular Signaling Peptides and Proteins/metabolism
• Mesenchymal Stem Cells/chemistry
• Mesenchymal Stem Cells/physiology
• Motor Neurons/cytology
• Motor Neurons/drug effects
• Neurites/drug effects
• Neurites/physiology
• Neurofilament Proteins/metabolism
• Rats
• Rats, Sprague-Dawley
• Spinal Cord/cytology

The mechanisms underlying the potentially beneficial effect of bone marrow stem cells (BMSCs) on spinal cord injury (SCI) are unknown. Therefore, the aim of the present study was to explore the protective effect of BMSCs in rats with SCI. A total of 45 adult male Sprague-Dawley rats were randomly divided into three groups; the SCI group (n=15), the BMSC group (n=15) and the sham-operation group (n=15). In the SCI and BMSC treatment groups, a modified Allen’s weight-drop technique was used to induce SCI. The BMSC treatment group received an injection of BMSCs using a microneedle into the epicenter of the spinal cord 24 h after injury. Rats in the sham-operation group were not subjected to SCI; however, the corresponding vertebral laminae were removed. Seven days after transplantation, a rapid recovery was observed in the Basso, Beattie and Bresnahan (BBB) scores of the BMSC treatment group, whereas the BBB scores in the SCI group remained low (P<0.05). Caspase-12 expression in the SCI group was increased compared with that in the sham-operation group, whereas caspase-12 expression was attenuated 24 h after transplantation in the BMSC treatment group (P<0.05). In conclusion, the transplantation of BMSCs may improve locomotor function and attenuate caspase-12 expression following SCI. Therefore, it is likely to be an effective strategy for preventing severe injury of the spinal cord.

• bone marrow stromal cells
• caspase-12
• endoplasmic reticulum stress
• spinal cord injury

• BMSCs
• GABAergic neurons
• combined therapy
• spinal cord injury

• Animals
• Bone Marrow Transplantation/methods
• Female
• Mesenchymal Stem Cells/physiology
• Nerve Regeneration/physiology
• Neurotransmitter Agents/metabolism
• Rats
• Rats, Sprague-Dawley
• Recovery of Function/physiology
• Spinal Cord Injuries/therapy
• gamma-Aminobutyric Acid/pharmacology

• msi
• maldi
• aplysia
• cell cultures

• Animals
• Aplysia/cytology
• Cells, Cultured
• Cytological Techniques
• Image Processing, Computer-Assisted
• Microscopy, Electron, Scanning
• Molecular Imaging/methods
• Neurons/chemistry
• Neurons/ultrastructure
• Neuropeptides/chemistry
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods

• 5R01 DA017940 NIDA NIH HHS
• P30 DA018310 NIDA NIH HHS
• P30 DA018310-06 NIDA NIH HHS
• P30 DA018310-05 NIDA NIH HHS
• R01 DA017940-05 NIDA NIH HHS
• R01 DE018866 NIDCR NIH HHS
• R01 DE018866-04 NIDCR NIH HHS
• R01 DA017940 NIDA NIH HHS
• 5R01 DE018866 NIDCR NIH HHS

• Bone marrow stromal cell
• cerebral stroke
• spinal cord injury
• translational study
• transplantation