Perspectives of researchers and clinicians on patient and public involvement (PPI) in preclinical spinal cord research: An interview study.

INTRODUCTION: Patient and public involvement (PPI) in research is an embedded practice in clinical research, however, its role in preclinical or laboratory-based research is less well established and presents specific challenges. This study aimed to explore the perspectives of two key stakeholder groups, preclinical researchers and clinicians on PPI in preclinical research, using spinal cord research as a case study. METHODS: Semi-structured interviews were conducted online with 11 clinicians and 11 preclinical researchers all working in the area of spinal cord injury (SCI). Interviews were transcribed verbatim and analysed thematically. FINDINGS: Nine themes were developed through analysis. Participants' perspectives included that people living with SCI had a right to be involved, that PPI can improve the relevance of preclinical research, and that PPI can positively impact the experiences of researchers. They identified the distance between lab-based research and the daily experiences of living with SCI to be a barrier and proactive management of accessibility and the motivated and networked SCI community as key facilitators. To develop strong partnerships, participants suggested setting clear expectations, ensuring good communication, and demonstrating respect for the time of PPI contributors involved in the research. CONCLUSIONS: While traditionally PPI has been more commonly associated with clinical research, participants identified several potential benefits of PPI in preclinical spinal cord research that have applicability to preclinical researchers more broadly. Preclinical spinal researchers should explore how to include PPI in their work. PATIENT OR PUBLIC CONTRIBUTION: This study was conducted as part of a broader project aiming to develop an evidence base for preclinical PPI that draws on a 5-year preclinical research programme focused on the development of advanced biomaterials for spinal cord repair as a case study. A PPI Advisory Panel comprising seriously injured rugby players, clinicians, preclinical researchers, and PPI facilitators collaborated as co-authors on the conceptualisation, design of the interview protocol, data analysis and writing of this manuscript.

The Development of Principles for Patient and Public Involvement (PPI) in Preclinical Spinal Cord Research: A Modified Delphi Study.

INTRODUCTION: There is currently limited guidance for researchers on Patient and Public Involvement (PPI) for preclinical spinal cord research, leading to uncertainty about design and implementation. This study aimed to develop evidence-informed principles to support preclinical spinal cord researchers to incorporate PPI into their research. METHODS: This study used a modified Delphi method with the aim of establishing consensus on a set of principles for PPI in spinal cord research. Thirty-eight stakeholders including researchers, clinicians and people living with spinal cord injury took part in the expert panel. Participants were asked to rate their agreement with a series of statements relating to PPI in preclinical spinal cord research over two rounds. As part of Round 2, they were also asked to rate statements as essential or desirable. RESULTS: Thirty-eight statements were included in Round 1, after which five statements were amended and two additional statements were added. After Round 2, consensus (> 75% agreement) was reached for a total of 27 principles, with 13 rated as essential and 14 rated as desirable. The principles with highest agreement related to diversity in representation among PPI contributors, clarity of the purpose of PPI and effective communication. CONCLUSION: This research developed a previously unavailable set of evidence-informed principles to inform PPI in preclinical spinal cord research. These principles provide guidance for researchers seeking to conduct PPI in preclinical spinal cord research and may also inform PPI in other preclinical disciplines. PATIENT AND PUBLIC INVOLVEMENT STATEMENT: This study was conducted as part of a project aiming to develop PPI in preclinical spinal cord injury research associated with an ongoing research collaboration funded by the Irish Rugby Football Union Charitable Trust (IRFU CT) and the Science Foundation Ireland Centre for Advanced Materials and BioEngineering Research (SFI AMBER), with research conducted by the Tissue Engineering Research Group (TERG) at the RCSI University of Medicine and Health Sciences. The project aims to develop an advanced biomaterials platform for spinal cord repair and includes a PPI Advisory Panel comprising researchers, clinicians and seriously injured rugby players to oversee the work of the project. PPI is included in this study through the involvement of members of the PPI Advisory Panel in the conceptualisation of this research, review of findings, identification of key points for discussion and preparation of the study manuscript as co-authors.

Biomaterials targeting the microenvironment for spinal cord injury repair: progression and perspectives.

Spinal cord injury (SCI) disrupts nerve pathways and affects sensory, motor, and autonomic function. There is currently no effective treatment for SCI. SCI occurs within three temporal periods: acute, subacute, and chronic. In each period there are different alterations in the cells, inflammatory factors, and signaling pathways within the spinal cord. Many biomaterials have been investigated in the treatment of SCI, including hydrogels and fiber scaffolds, and some progress has been made in the treatment of SCI using multiple materials. However, there are limitations when using individual biomaterials in SCI treatment, and these limitations can be significantly improved by combining treatments with stem cells. In order to better understand SCI and to investigate new strategies for its treatment, several combination therapies that include materials combined with cells, drugs, cytokines, etc. are summarized in the current review.

DLP printed hDPSC-loaded GelMA microsphere regenerates dental pulp and repairs spinal cord.

Dental pulp regeneration is ideal for irreversible pulp or periapical lesions, and in situ stem cell therapy is one of the most effective therapies for pulp regeneration. In this study, we provided an atlas of the non-cultured and monolayer cultured dental pulp cells with single-cell RNA sequencing and analysis. Monolayer cultured dental pulp cells cluster more closely together than non-cultured dental pulp cells, suggesting a lower heterogeneous population with relatively consistent clusters and similar cellular composition. We successfully fabricated hDPSC-loaded microspheres by layer-by-layer photocuring with a digital light processing (DLP) printer. These hDPSC-loaded microspheres have improved stemness and higher multi-directional differentiation potential, including angiogenic, neurogenic, and odontogenic differentiation. The hDPSC-loaded microspheres could promote spinal cord regeneration in rat spinal cord injury models. Moreover, in heterotopic implantation tests on nude mice, CD31, MAP2, and DSPP immunofluorescence signals were observed, implying the formation of vascular, neural, and odontogenetic tissues. In situ experiments in minipigs demonstrated highly vascularized dental pulp and uniformly arranged odontoblast-like cells in root canals of incisors. In short, hDPSC-loaded microspheres can promote full-length dental pulp regeneration at the root canals' coronal, middle, and apical sections, particularly for blood vessels and nerve formation, which is a promising therapeutic strategy for necrotic pulp.

Knockdown of polypyrimidine tract binding protein facilitates motor function recovery after spinal cord injury.

After spinal cord injury (SCI), a fibroblast- and microglia-mediated fibrotic scar is formed in the lesion core, and a glial scar is formed around the fibrotic scar as a result of the activation and proliferation of astrocytes. Simultaneously, a large number of neurons are lost in the injured area. Regulating the dense glial scar and replenishing neurons in the injured area are essential for SCI repair. Polypyrimidine tract binding protein (PTB), known as an RNA-binding protein, plays a key role in neurogenesis. Here, we utilized short hairpin RNAs (shRNAs) and antisense oligonucleotides (ASOs) to knock down PTB expression. We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro. In a mouse model of compression-induced SCI, adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area. Basso Mouse Scale scores and forced swim, inclined plate, cold allodynia, and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI. Furthermore, ASO-mediated PTB knockdown improved motor function restoration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure. Together, these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.

Circulating exosomal lncRNA contributes to the pathogenesis of spinal cord injury in rats.

Exosome-derived long non-coding RNAs (lncRNAs) are extensively engaged in recovery and repair of the injured spinal cord, through different mechanisms. However, to date no study has systematically evaluated the differentially expressed lncRNAs involved in the development of spinal cord injury. Thus, the aim of this study was to identify key circulating exosome-derived lncRNAs in a rat model of spinal cord injury and investigate their potential actions. To this end, we established a rat model of spinal cord hemisection. Circulating exosomes were extracted from blood samples from spinal cord injury and control (sham) rats and further identified through Western blotting and electron microscopy. RNA was isolated from the exosomes and sequenced. The enrichment analysis demonstrated that there were distinctively different lncRNA and mRNA expression patterns between the two groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) functional analysis were performed to determine the possible involvements of upregulated and downregulated lncRNAs in various pathways and different biological processes, as well as their cellular locations and molecular functions. Furthermore, quantitative reverse transcription-polymerase chain reaction showed that the expression of five lncRNAs--ENSRN0T00000067908, XR_590093, XR_591455, XR_360081, and XR_346933--was increased, whereas the expression of XR_351404, XR_591426, XR_353833, XR_590076, and XR_590719 was decreased. Of note, these 10 lncRNAs were at the center of the lncRNA-miRNA-mRNA coexpression network, which also included 198 mRNAs and 41 miRNAs. Taken together, our findings show that several circulating exosomal lncRNAs are differentially expressed after spinal cord injury, suggesting that they may be involved in spinal cord injury pathology and pathogenesis. These lncRNAs could potentially serve as targets for the clinical diagnosis and treatment of spinal cord injury.

Microsurgical repair of severed thoracic spinal cord and clinical outcome: technical case report.

BACKGROUND: This report describes a case of successful repair of severed thoracic spine in a young man who presented with a penetrating stab injury to spine resulting in Brown-Séquard syndrome. Surgical technique and post-operative management is discussed. CASE PRESENTATION: A 34-year-old fit and well healthy man was admitted with a history of stab injury to the thoracic spine at thoracic T2/3 level with ASIA impairment score (AIS) score D with an incomplete spinal cord affecting his left lower limb with complete paralysis and right lower limb paresis with impaired sensation below T6 level to L5. Neuroimaging confirmed a penetrating knife injury traversing the T2/3 level causing hemi-section of the spinal cord confirmed intraoperatively. He underwent an urgent exploratory surgery of his spine and a T2/3 laminectomy was performed to aid removal of the knife. The dura was noted to be contused and severed spinal cord was noted to be severed with associated cord oedema. A microsurgical repair of the severed cord was performed with duroplasty followed by intense neuro-rehabilitation. On a 3 month follow up his AIS score is E with lower limb power is 5/5 bilaterally and he is able to mobilise independently up to 8-10 steps without any supportive aid and with crutches he is independently functional and mobile. CONCLUSION: This is the first documented case of microsurgical repair of severed thoracic spinal cord secondary to traumatic knife injury. In the management of such scenario, apart from the removal of foreign body, repair of the cord with duroplasty should be carefully considered. The role of spinal neuroplasticity in healing following timely repair of the spinal cord along with intense rehabilitation remains the key. This had resulted in a good clinical and functional outcome with in a 18-month follow up.

Cell Therapies for Spinal Cord Injury: Trends and Challenges of Current Clinical Trials.

Cell therapies have the potential to revolutionize the treatment of spinal cord injury. Basic research has progressed significantly in recent years, with a plethora of cell types now reaching early-phase human clinical trials, offering new strategies to repair the spinal cord. However, despite initial enthusiasm for preclinical and early-phase clinical trials, there has been a notable hiatus in the translation of cell therapies to routine clinical practice. Here, we review cell therapies that have reached clinical trials for spinal cord injury, providing a snapshot of all registered human trials and a summary of all published studies. Of registered trials, the majority have used autologous cells and approximately a third have been government funded, a third industry sponsored, and a third funded by university or healthcare systems. A total of 37 cell therapy trials have been published, primarily using stem cells, although a smaller number have used Schwann cells or olfactory ensheathing cells. Significant challenges remain for cell therapy trials in this area, including achieving stringent regulatory standards, ensuring appropriately powered efficacy trials, and establishing sustainable long-term funding. However, cell therapies hold great promise for human spinal cord repair and future trials must continue to capitalize on the exciting developments emerging from preclinical studies.

Multichannel Bioactive Silk Nanofiber Conduits Direct and Enhance Axonal Regeneration after Spinal Cord Injury.

After a spinal cord injury, axonal regeneration over long distances is challenging due to the lack of physical guidance cues and bioactive signals. In this study, a multichannel bioactive silk fibroin nanofiber conduit was fabricated to improve spinal cord injury repair by enhancing axonal regeneration. The conduit was composed of longitudinally oriented silk fibroin nanofibers and then functionalized with laminin. In vitro, the bioactive conduits could promote neuron-like development and directional neurite extension of PC12 cells by providing a bioactive stimulus and physical guidance. In a spinal cord injury model in Sprague-Dawley rats, the biofunctionalized conduits displayed superior integration with the host tissue due to enhanced cell infiltration and tissue ingrowth. The glial scar was significantly reduced, allowing axonal ingrowth along with the channel direction. Compared to a single-channel conduit, the multichannel conduit improved spinal cord regeneration by boosting tissue ingrowth and axonal regeneration, indicating that the conduit architectures play critical roles in spinal cord regeneration. These silk fibroin conduits, along with the multichannel architecture, nanoscale cues, and the ability to bind bioactive compounds, represent promising candidates for spinal cord regeneration.

Use of ebselen as a neuroprotective agent in rat spinal cord subjected to traumatic injury.

Spinal cord injury (SCI) causes disturbances of motor skills. Free radicals have been shown to be essential for the development of spinal cord trauma. Despite some progress, until now no effective pharmacological therapies against SCI have been verified. The purpose of our experiment was to investigate the neuroprotective effects of ebselen on experimental SCI. Twenty-two rats subjected to SCI were randomly subjected to SCI with no further treatment (n = 10) or intragastric administration of ebselen (10 mg/kg) immediately and 24 hours after SCI. Behavioral changes were assessed using the Basso, Beattie, and Bresnahan locomotor scale and footprint test during 12 weeks after SCI. Histopathological and immunohistochemical analyses of spinal cords and brains were performed at 12 weeks after SCI. Magnetic resonance imaging analysis of spinal cords was also performed at 12 weeks after SCI. Rats treated with ebselen presented only limited neurobehavioral progress as well as reduced spinal cord injuries compared with the control group, namely length of lesions (cysts/scars) visualized histopathologically in the spinal cord sections was less but cavity area was very similar. The same pattern was found in T2-weighted magnetic resonance images (cavities) and diffusion-weighted images (scars). The number of FluoroGold retrogradely labeled neurons in brain stem and motor cortex was several-fold higher in ebselen-treated rats than in the control group. The findings suggest that ebselen has only limited neuroprotective effects on injured spinal cord. All exprimental procedures were approved by the Local Animal Ethics Committee for Experiments on Animals in Katowice (Katowice, Poland) (approval No. 19/2009).

Hair Follicle-Associated Pluripotent(HAP) Stem Cells.

The hair follicle has been known, since 1990, to contain stem cells located in the bulge area. In 2003, we reported a new type of stem cell in the hair follicle that expresses the brain stem-cell marker nestin. We have termed these cells as hair-follicle-associated pluripotent (HAP) stem cells. HAP stem cells can differentiate into neuronal and glial cells, beating cardiac-muscle cells, and other cell types in culture. HAP stem cells can be used for nerve and spinal-cord repair such that locomotor activity is recovered. A major function in situ of the HAP stem cells is for growth of the hair follicle sensory nerve. HAP stem cells have critical advantages over embryonic stem cells and induced pluripotent stem (IPS) cells for regenerative medicine in that they are highly accessible, require no genetic manipulation, are nontumorigenic, and do not present ethical issues.

From transplanting Schwann cells in experimental rat spinal cord injury to their transplantation into human injured spinal cord in clinical trials.

Among the potential therapies designed to repair the injured spinal cord is cell transplantation, notably the use of autologous adult human Schwann cells (SCs). Here, we detail some of the critical research accomplished over the last four decades to establish a foundation that enables these cells to be tested in clinical trials. New culture systems allowed novel information to be gained about SCs, including discovering ways to stimulate their proliferation to acquire adequately large numbers for transplantation into the injured human spinal cord. Transplantation of rat SCs into rat models of spinal cord injury has demonstrated that SCs promote repair of injured spinal cord. Additional work required to gain approval from the Food and Drug Administration for the first SC trial in the Miami Project is disclosed. This trial and a second one now underway are described.

From the Rodent Spinal Cord Injury Model to Human Application: Promises and Challenges.

Repair of the spinal cord and improvement of mobility after injury has been a matter of basic and clinical research for several decades. A number of repair approaches were performed in animals, mainly rodent models of spinal cord injury (SCI). Some of these experimental therapies resulted in significant regeneration of tract fibers, formation of new connections and circuits, and associated improvement of mobility. Some clinical trials aiming at translating these approaches to the human condition of an SCI are currently on-going. The present therapy, however, remains rehabiliation: Mobility of patients with an SCI can be improved to a limited extent by the exploition of neuroplasticity. In this article the present state of the art in the field of SCI research will be discussed. Studies dealing with the promotion of spinal cord repair and those directed to improve mobility by exploition of neuroplasticity will be summarized. The promises and challenges of translational basic research in rodent SCI models will be presented.

Biomechanical properties of the spinal cord: implications for tissue engineering and clinical translation.

Spinal cord injury is a severely debilitating condition which can leave individuals paralyzed and suffering from autonomic dysfunction. Regenerative medicine may offer a promising solution to this problem. Previous research has focused primarily on exploring the cellular and biological aspects of the spinal cord, yet relatively little remains known about the biomechanical properties of spinal cord tissue. Given that a number of regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding the biomechanical properties of host spinal cord tissue is important. We review the relevant biomechanical properties of spinal cord tissue and provide the baseline knowledge required to apply these important physical concepts to spinal cord tissue engineering.

Introduction to Hair-Follicle-Associated Pluripotent Stem Cells.

Nestin-expressing stem cells of the hair follicle, discovered by our laboratory, have been shown to be able to form outer-root sheaths of the follicle as well as neurons and many other non-follicle cell types. We have termed the nestin-expressing stem cells of the hair follicle as hair-follicle-associated pluripotent (HAP) stem cells. We have shown that the HAP stem cells from the hair follicle can effect the repair of peripheral nerve and spinal cord injury. The hair follicle stem cells differentiate into neuronal and glial cells after transplantation to the injured peripheral nerve and spinal cord, and enhance injury repair and locomotor recovery. When the excised hair follicle with its nerve stump was placed in Gelfoam(®) 3D histoculture, HAP stem cells grew and extended the hair follicle nerve which consisted of ßIII-tubulin-positive fibers with F-actin expression at the tip. These findings indicate that ßIII-tubulin-positive fibers elongating from the whisker follicle sensory nerve stump were growing axons. The growing whisker sensory nerve was highly enriched in HAP stem cells, which appeared to play a major role in its elongation and interaction with other nerves in 3D Gelfoam(®) histoculture, including the sciatic nerve, the trigeminal nerve, and the trigeminal nerve ganglion. These results suggest that a major function of the HAP stem cells in the hair follicle is for growth of the follicle sensory nerve. Recently, we have shown that HAP stem cells can differentiate into beating cardiac muscle cells. HAP stem cells have critical advantages for regenerative medicine over embryonic stem (ES) cells and induced pluripotent stem (iPS) cells in that they are highly accessible from each patient, thereby eliminating immunological issues since they are autologous, require no genetic manipulation, are non-tumorigenic, and do not present ethical issues.

Improving outcome of sensorimotor functions after traumatic spinal cord injury.

In the rehabilitation of a patient suffering a spinal cord injury (SCI), the exploitation of neuroplasticity is well established. It can be facilitated through the training of functional movements with technical assistance as needed and can improve outcome after an SCI. The success of such training in individuals with incomplete SCI critically depends on the presence of physiological proprioceptive input to the spinal cord leading to meaningful muscle activations during movement performances. Some actual preclinical approaches to restore function by compensating for the loss of descending input to spinal networks following complete/incomplete SCI are critically discussed in this report. Electrical and pharmacological stimulation of spinal neural networks is still in the experimental stage, and despite promising repair studies in animal models, translations to humans up to now have not been convincing. It is possible that a combination of techniques targeting the promotion of axonal regeneration is necessary to advance the restoration of function. In the future, refinement of animal models according to clinical conditions and requirements may contribute to greater translational success.

A Proposal for a Rat Model of Spinal Cord Injury Featuring the Rubrospinal Tract and its Contributions to Locomotion and Skilled Hand Movement.

Spinal cord injury and repair is a dynamic field of research. The development of reliable animal models of traumatic spinal cord injury has been invaluable in providing a wealth of information regarding the pathological consequences and recovery potential of this condition. A number of injury models have been instrumental in the elaboration and the validation of therapeutic interventions aimed at reversing this once thought permanent condition. In general, the study of spinal cord injury and repair is made difficult by both its anatomical complexity and the complexity of the behavior it mediates. In this perspective paper, we suggest a new model for spinal cord investigation that simplifies problems related to both the functional and anatomical complexity of the spinal cord. We begin by reviewing and contrasting some of the most common animal models used for investigating spinal cord dysfunction. We then consider two widely used models of spinal deficit-recovery, one involving the corticospinal tracts (CTS) and the other the rubrospinal tract (RST). We argue that the simplicity of the function of the RST makes it a useful model for studying the cord and its functional repair. We also reflect on two obstacles that have hindered progress in the pre-clinical field, delaying translation to the clinical setup. The first is recovery of function without reconnection of the transected descending fibers and the second is the use of behavioral paradigms that are not under the control of the descending fiber pathway under scrutiny.

SIKVAV-modified highly superporous PHEMA scaffolds with oriented pores for spinal cord injury repair.

The architecture and mechanical properties of a scaffold for spinal cord injury treatment must provide tissue integration as well as effective axonal regeneration. Previous work has demonstrated the cell-adhesive and growth-promoting properties of the SIKVAV (Ser-Ile-Lys-Val-Ala-Val)-modified highly superporous poly(2-hydroxethyl methacrylate) (PHEMA) hydrogels. The aim of the current study was to optimize the porosity and mechanical properties of this type of hydrogel in order to develop a suitable scaffold for the repair of spinal cord tissue. Three types of highly superporous PHEMA hydrogels with oriented pores of ~60 µm diameter, porosities of 57-68% and equivalent stiffness characterized by elasticity moduli in the range 3-45 kPa were implanted into a spinal cord hemisection, and their integration into the host tissue, as well as the extent of axonal ingrowth into the scaffold pores, were histologically evaluated. The best tissue response was found with a SIKVAV-modified PHEMA hydrogel with 68% porosity and a moderate modulus of elasticity (27 kPa in the direction along the pores and 3.6 kPa in the perpendicular direction). When implanted into a spinal cord transection, the hydrogel promoted tissue bridging as well as aligned axonal ingrowth. In conclusion, a prospective oriented scaffold architecture of SIKVAV-modified PHEMA hydrogels has been developed for spinal cord injury repair; however, to develop an effective treatment for spinal cord injury, multiple therapeutic approaches are needed.

Interaction of polyethylene glycol (PEG) with the membrane-binding domains following spinal cord injury (SCI): introduction of a mechanism for SCI repair.

Lipid-binding domains regulate positioning of the membrane proteins via specific interactions with phospholipid's head groups. Spinal cord injury (SCI) diminishes the integrity of neural fiber membranes at nanoscopic level. In cases that the ruptured zone size is beyond the natural resealing ability, there is a need for reinforcing factors such as polymers (e.g. Polyethylene glycol) to patch the dismantled axoplasm. Certain conserved sequential and structural patterns of interacting residues specifically bind to PEGs. It is also found that PEG600, PEG400 and PEG200 share the strongest interaction with the lipid-binding domains even more successful than phospholipid head groups. The alpha helix structure composed of hydrophobic, neutral and acidic residues prepares an opportunity for PEG400 to play an amphipathic role in the interaction with injured membrane. This in-silico study introduces a mechanism for PEG restorative ability at the molecular level. It is believed that PEG400 interrelates the injured membrane to their underneath axoplasm while retaining the integrity of ruptured membrane via interaction with ENTH domains of membrane proteins. This privilege of PEG400 in treating injured membrane must be considered in designing of polymeric biomaterials that are introduced for SCI repair.

Stem cell injection in the hindlimb skeletal muscle enhances neurorepair in mice with spinal cord injury.

AIMS: To develop a low-risk, little-invasive stem cell-based method to treat acute spinal cord injuries. methods: Adult mice were submitted to an incomplete spinal cord injury, and mesenchymal stem cells injected intramuscularly into both hindlimbs. Behavior tests and MRI of the spinal cord were periodically performed for up to 6 months, along with immunohistochemical analysis. Immunohistochemical and PCR analysis of the muscles were used to detect the grafted cells as well as the soluble factors released. RESULTS: The stem cell-treated mice presented significant improvements in their motor skills 5 months after treatment. Spinal cord repair was detected by magnetic resonance and immunohistochemistry. In the hindlimb muscles, the stem cells activated muscle and motor neuron repair mechanisms, due to the secretion of several neurotrophic factors. CONCLUSION: Bone marrow mesenchymal stem cell injection into hindlimb muscles stimulates spinal cord repair in acute spinal cord lesions.