Traumatic spinal cord injury (SCI) is a life-altering condition that results in long-term complications, including progressive neurodegeneration and cord atrophy. It presents a significant unmet medical need with extensive social and economic burdens.

To evaluate the safety and preliminary efficacy of allogeneic mesenchymal stem cells derived from Wharton’s jelly (WJ-MSCs) in patients with chronic complete SCI. The primary objective was to assess whether WJ-MSCs could facilitate neurological recovery and improve the quality of life in this patient population.

This open-label, multicenter phase I study investigated the effects of administering WJ-MSCs via three delivery routes: Intrathecal (for localized spinal targeting); intramuscular (for targeting end organ); and intravenous (for systemic immunomodulation). While all three routes were used concurrently to enhance therapeutic synergy, neurological, sensory, and functional scales were used to assess overall efficacy. Participants with chronic SCI (duration of at least 6 months) who had significant impairment and disability were eligible for inclusion. WJ-MSCs were administered twice monthly for 2 months, with each route receiving a dose of 1 × 10⁶ cells/kg. Patients were closely monitored for 1 year following treatment.

At baseline, participants displayed considerable functional deficits, as indicated by the following scores: Functional independence measure of 77.5 ± 2.26; Modified Ashworth Scale of 15.83 ± 4.83; American Spinal Injury Association (ASIA) Motor score of 1.67 ± 2.66; ASIA Light Touch and Pin-Prick scores of 62 ± 18.42 each; Wexner Incontinence Score of 20; and Qualiveen Short Form, a validated questionnaire specifically designed to assess the impact of urinary dysfunction on quality of life in individuals with SCI, score of 32. Following WJ-MSC therapy, significant improvements were observed in all neurological functions over the 1-year follow-up. Notably, the ASIA Motor score improved significantly (χ² = 23.938, P < 0.001), and Qualiveen Short Form scores demonstrated a substantial enhancement in quality of life (z = -2.214, P < 0.05).

This phase I study, conducted without a control group, suggests that the administration of WJ-MSCs through multiple routes is both safe and potentially effective in patients with chronic complete SCI. However, the observed neurological improvements cannot be solely attributed to WJ-MSC therapy, as concurrent pharmacological and rehabilitative interventions were not controlled. These findings indicated that WJ-MSC therapy may offer a promising approach for enhancing neurological function and quality of life in this challenging patient population. Further research with larger cohorts and extended follow-up is necessary to validate these preliminary results.

• Spinal cord injury
• Mesenchymal stem cell
• Transplantation
• Wharton’s jelly
• Neurological recovery

• adipose-derived
• autologous
• case report
• mesenchymal stem cells
• spinal cord injury
• transplantation

• Adipose tissue
• Adipose tissue–derived stem cells
• Allograft
• Cell morphology
• Heterogeneity

• Adipose Tissue
• Adipocytes/metabolism
• Transplantation, Homologous
• Cell Differentiation
• Stem Cells
• Allografts

• 203/PPSP/6171291 Ministry of Higher Education, Malaysia

• degenerative myelopathy
• dogs
• electrical stimulation
• intensive neurorehabilitation
• locomotor training
• mesenchymal stem cells

• Fundação para a Ciência e a Tecnologia
• Agência Nacional de Inovação

• Adipose-derived mesenchymal stem cells (ADSCs)
• Cell sheets
• Cell-based therapy
• Neurogenic bladder (NB)
• Spinal cord injury (SCI)

• exosome
• extracellular vesicle
• mesenchymal stem cell
• spinal cord injury

• Animals
• Disease Models, Animal
• Extracellular Vesicles/genetics
• Extracellular Vesicles/metabolism
• Extracellular Vesicles/transplantation
• Humans
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells/metabolism
• Spinal Cord Injuries/therapy

• Animal study
• Meta-analysis
• Spinal cord injuries
• Stem cell

• AD-MSCs
• BM-MSCs
• ESCs
• EVs
• NPCs
• NSCs
• U-MSCs
• iPSCs
• spinal cord injury
• stem cells

Angiogenesis is considered to mediate the beneficial effects of mesenchymal cell therapy in spinal cord injury. After a moderate balloon-compression injury in rats, injections of either human adipose tissue-derived stromal/stem cells (hADSCs) or their conditioned culture media (CM-hADSC) elicited angiogenesis around the lesion site. Both therapies increased vascular density, but the presence of hADSCs in the tissue was required for the full maturation of new blood vessels. Only animals that received hADSC significantly improved their open field locomotion, assessed by the BBB score. Animals that received CM-hADSC only, presented haemorrhagic areas and lack pericytes. Proteomic analyses of human angiogenesis-related factors produced by hADSCs showed that both pro- and anti-angiogenic factors were produced by hADSCs in vitro, but only those related to vessel maturation were detectable in vivo. hADSCs produced PDGF-AA only after insertion into the injured spinal cord. hADSCs attracted resident pericytes expressing NG2, α-SMA, PDGF-Rβ and nestin to the lesion, potentially contributing to blood vessel maturation. We conclude that the presence of hADSCs in the injured spinal cord is essential for tissue repair.

• Apoptosis
• Epidural fat-mesenchymal stem cells extracellular vesicles (EF-MSCs-extracellular vesicles)
• Functional recovery
• NLRP3 inflammasome
• Spinal cord injury (SCI)

• Adult astrocyte
• Conversion
• In vivo reprogramming
• Neural stem cells
• Reprogramming
• Spinal cord injury
• Zfp521

• Animals
• Astrocytes/metabolism
• Disease Models, Animal
• Gene Expression Regulation/genetics
• Male
• Neural Stem Cells/metabolism
• Neurons/metabolism
• Rats
• Rats, Sprague-Dawley
• Spinal Cord Injuries/genetics
• Transcription Factors/genetics
• Zinc Fingers/genetics

• Royan Institute

Mesenchymal stem cells (MSCs) and their cellular response to various stimuli have been characterized in great detail in culture conditions. In contrast, the cellular response of MSCs in an in vivo setting is still uncharted territory. In this study, we investigated the cellular response of MSCs following transplantation into spinal cord injury (SCI).

Mouse bone marrow-derived MSCs were transplanted 24 h following severe contusion SCI in mice. As controls, MSCs transplanted to the uninjured spinal cord and non-transplanted MSCs were used. At 7 days post transplantation, the MSCs were isolated from the SCI, and their global transcriptional changes, survival, differentiation, proliferation, apoptosis, and phenotypes were investigated using RNA sequencing, immunohistochemistry, and flow cytometry.

MSCs transplanted into SCI downregulated genes related to cell-cycle regulation/progression, DNA metabolic/biosynthetic process, and DNA repair and upregulated genes related to immune system response, cytokine production/response, response to stress/stimuli, signal transduction and signaling pathways, apoptosis, and phagocytosis/endocytosis. MSCs maintained their surface expression of Sca1 and CD29 but upregulated expression of CD45 following transplantation. Transplanted MSCs maintained their surface expression of MHC-I but upregulated surface expression of MHC-II. Transplanted MSCs survived and proliferated to a low extent, did not express Caspase-3, and did not differentiate into neurons or astrocytes.

MSCs transplanted into SCI upregulate expression of CD45 and MHC-II and expression of genes related to cytokine production, phagocytosis/endocytosis, and immune cells/response and thereby adopt immune cell-like characteristics within the recipient.

The online version of this article (10.1186/s13287-019-1218-9) contains supplementary material, which is available to authorized users.

• Cellular response
• Differentiation
• Graft survival
• Mesenchymal stem cells
• Phenotypes
• Proliferation
• Spinal cord injury
• Transcriptional changes

Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI.

rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, S100β, brain derived neurotrophic factor (BDNF), 2’,3’-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor [TGF]-β, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors.

rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), β3-tubulin and nestin as well as antiinflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined.

Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

• Islets of langerhans
• Regeneration
• Spinal cord
• Stem cells
• Wounds and injuries

Peripheral nerve injury (PNI) is a worldwide issue associated with severe social and economic burden. Autologous nerve grafting, the gold standard treatment for peripheral nerve defects, still has a number of technical limitations. Tissue engineering technology is a novel therapeutic strategy, and mesenchymal stromal cells (MSCs) are promising seed cells for nerve tissue engineering. However, the efficiency of traditional methods for inducing the differentiation of MSCs to Schwann cell-like cells (SCLCs) remains unsatisfactory.

Here, we propose an intermittent induction method with alternate use of complete and incomplete induction medium to induce differentiation of adipose-derived stem cells (ASCs) to SCLCs. The time dependence of traditional induction methods and the efficiency of the intermittent induction method and traditional induction methods were evaluated and compared using immunocytochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and co-culture with the dorsal root ganglion (DRG) in vitro. Cell transplantation was used to compare the effects of the traditional induction method and the intermittent induction method in repairing sciatic nerve defects in vivo.

The results of the present study indicated that the intermittent induction method is more efficient than traditional methods for inducing ASCs to differentiate into SCLCs. In addition, SCLCs induced by this method were closer to mature myelinating Schwann cells and were capable of secreting neurotrophins and promoting DRG axon regeneration in vitro. Furthermore, SCLCs induced by the intermittent induction method could repair sciatic nerve defects in rats by cell transplantation in vivo more effectively than those produced by traditional methods.

Intermittent induction represents a novel strategy for obtaining seed cells for use in nerve tissue engineering.

The online version of this article (10.1186/s13287-018-0884-3) contains supplementary material, which is available to authorized users.

• Adipose-derived stem cells
• Cell transplantation
• Differentiation
• Intermittent induction
• Peripheral nerve regeneration
• Schwann cell-like cells

• spinal cord injuries
• wistar rats
• granulocyte colony-stimulating factor
• methylprednisolone

• Animals
• Disease Models, Animal
• Drug Combinations
• Granulocyte Colony-Stimulating Factor/pharmacokinetics
• Male
• Methylprednisolone/pharmacokinetics
• Neuroprotective Agents/pharmacokinetics
• Random Allocation
• Rats, Wistar
• Recovery of Function/drug effects
• Reference Values
• Reproducibility of Results
• Spinal Cord Injuries/drug therapy
• Spinal Cord Injuries/pathology
• Spinal Cord Injuries/rehabilitation
• Time Factors
• Treatment Outcome