Safety and possible outcome assessment of autologous Schwann cell and bone marrow mesenchymal stromal cell co-transplantation for treatment of patients with chronic spinal cord injury.

BACKGROUND AIMS: Cell replacement therapy has become a promising issue that has raised much hope in the regeneration of central nervous system injury. Evidence indicates that successful functional recovery in patients with spinal cord injury will not simply emphasize a single therapeutic strategy. Therefore, many recent studies have used combination strategies for spinal cord regeneration. METHODS: We assessed the safety and feasibility of a bone marrow mesenchymal stromal cell and Schwann cell combination for the treatment of patients with chronic spinal cord injury. Eight subjects who received a complete traumatic spinal cord injury (American Spinal Injury Association [ASIA] classification A) enrolled in this study. The patients received this autologous combination of cells directly into the injury site. The mean duration of follow-up was approximately 24 months. RESULTS: No magnetic resonance imaging evidence of neoplastic tissue overgrowth, syringomyelia or psuedomeningocele in any of the patients was seen during the study. There was no deterioration in sensory or motor function in any of the patients during the course of the study. Three patients had negligible improvement in ASIA sensory scale. No motor score improvement and no change in ASIA classification was seen. The patients had widely subjective changes in the course of the study such as urination and defecation sensation and more stability and trunk equilibrium in the sitting position. CONCLUSIONS: There were no adverse findings at least 2 years after autologous transplantation of Schwann cell and mesenchymal stromal cell combination into the injured spinal cord. It appears that the use of this combination of cells is safe for clinical application to spinal cord regeneration.

A comparison between neurally induced bone marrow derived mesenchymal stem cells and olfactory ensheathing glial cells to repair spinal cord injuries in rat.

Cell therapy has proven to be a highly promising method in clinical applications, raising so much hope for the treatment of injured tissues with low, if any, self regeneration potential such as central and peripheral nervous system. Neurally induced bone marrow derived mesenchymal stem cells (NIMSCs) as well as olfactory ensheathing cells (OECs) were transplanted in a rat model of sub-acute spinal cord injury and the behavioral and histological analyses were conducted. A balloon-compression technique was used to produce an injury at T8-T9 level of spinal cord. After a week post injury, rats were injected with either NIMSCs or OECs at the center of developing lesion cavity, 3mm cranial and 3mm caudal to the cavity. Weekly behavioral assessment using BBB score was done over five-week period post transplantation and finally histological assessment was performed to locate labeled cells in the tissue in order to evaluate the reduction of cavity formation and axonal regeneration. Evaluation of locomotor performance showed significant behavioral improvement in NIMSC group over OEC and control groups. The histological analyses revealed the presence of transplanted cells in the spinal cord parenchyma. Volume of injured area that was occupied with syrinx cavity in NIMSC group was significantly less than control group. In addition, meanwhile neurofilament-positive axons significantly showed higher expression in rats receiving NIMSC compared to the other two groups. In conclusion NIMSC caused both behavioral and histological improvement that potentially makes them a promising candidate for cell therapy approaches of spinal cord injuries.

Effects of low level laser therapy on proliferation and neurotrophic factor gene expression of human schwann cells in vitro.

Previous studies have been proposed that proliferation and release of certain growth factors by different types of cells can be modulated by low level laser therapy. We aimed to demonstrate the effect of laser irradiation on human schwann cell proliferation and neurotrophic factor gene expression in vitro. Human schwann cells (SCs) were harvested from sural nerve that was obtained from organ donor followed by treatment with an 810 nm, 50 mW diode laser (two different energies: 1 J/cm(2) and 4 J/cm(2)) in three consecutive days. SC proliferation was measured, after first irradiation on days 1, 4 and 7 by the MTT assay. Real time PCR analysis was utilized on days 5 and 20 to evaluate the expression of key genes involved in nerve regeneration consist of NGF, BDNF and GDNF. Evaluation of cellular proliferation following one day after laser treatment revealed significant decrease in cell proliferation compared to control group. However on day 7, significant increase in proliferation was found in both the irradiated groups in comparison with the control group. No significant difference was found between the laser treated groups. Treatment of SCs with laser resulted in significant increase in NGF gene expression on day 20. Difference between two treated groups and control group was not significant for BDNF and GDNF gene expression. Our results demonstrate that low level laser therapy stimulate human schwann cell proliferation and NGF gene expression in vitro.

Nasal septum-derived multipotent progenitors: a potent source for stem cell-based regenerative medicine.

Thus far, autologous adult stem cells have attracted great attention for clinical purposes. In this study, we aimed at identifying and comprehensively characterizing a subpopulation of multipotent cells within human nasal septal cartilage. We also conducted a comparative investigation with other well-established stem cells such as bone marrow-mesenchymal stem cells, adipose tissue-mesenchymal stem cells, and unrestricted somatic stem cells. The isolated clonal population was characterized using immunofluorescence, flow cytometry, reverse transcriptase, and real-time polymerase chain reaction. Nasal septal progenitors (NSP) expressed critical pluripotency and mesoectodermal stem cell markers. They also shared many characteristics with MSC in expression of CD90, CD105, CD106, CD166, and HLA-ABC and lack of expression of CD34, CD45, and HLA-DR. NSP distinctly presented CD133 (Prominin-1). These cells could proliferate rapidly in vitro with a higher clonogenic potential and showed a longer lifespan than other studied cells. This population bears some other multipotent properties in showing a high capacity to be differentiated into other lineages including chondrocytes, osteocytes, and neural-like cell types. Another strong/positive feature of this population was their ability to be safely expanded ex vivo with no susceptibility to chromosomal abnormality or tumorigenicity both in vitro and in vivo. In conclusion, NSP could be considered as an alternative autologous cell source that can bring them to the top of therapeutic applications.