Transplantation of a combination of autologous neural differentiated and undifferentiated mesenchymal stem cells into injured spinal cord of rats

Abstract

Study design: The use of stem cells for functional recovery after spinal cord injury. Objective: The aim of this study was to evaluate the effects of a combination of autologous undifferentiated and neural-induced bone marrow mesenchymal stem cells (MSCs) on behavioral improvement in rats after inducing spinal cord injury and comparing with transplantation of undifferentiated and neural-induced MSCs alone. Setting: The study was conducted at the department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. Methods: The spinal cord was injured by contusion using a Fogarty embolectomy catheter at the T8-T9 level of the spinal cord, and autologous MSCs were transplanted into the center of the developing lesion cavity, 3 mm cranial and 3 mm caudal to the cavity, at 7 days after induction of spinal cord compression injury. Results: At 5 weeks after transplantation, the presence of transplanted cells was detected in the spinal cord parenchyma using immunohistochemistry analysis. In all treatment groups (differentiated, undifferentiated and mix), there was less cavitation than lesion sites in the control group. The BassoBeattie-Bresnahan (BBB) score was significantly higher in rats transplanted with a combination of cells and in rats transplanted with neural-induced MSCs alone than in undifferentiated and control rats. Conclusion: Pre-differentiation of MSCs to neuron-like cells has a very important role in achieving the best results for functional improvement.

The Secretome of Bone Marrow and Wharton Jelly Derived Mesenchymal Stem Cells Induces Differentiation and Neurite Outgrowth in SH-SY5Y Cells

“…The underlying mechanisms by which the MSCs transplantation mediates the beneficial outcomes remain to be elucidated. Although the putative MSCs differentiation into neuronal lineages has been purposed as the major contributor for CNS regeneration in animal models of neurodegenerative diseases [11–15], MSCs differentiation into full functional neuronal lineages remains to be clarified [16–18]. In contrast, robust data indicates that CNS tissue restorative effects are mediated by MSCs secretome, that is, the panel of bioactive factors and vesicles, with neuroregulatory properties, released by these cells to the extracellular environment [10, 19–42].…”

Bridging defects in chronic spinal cord injury using peripheral nerve grafts combined with a chitosan-laminin scaffold and enhancing regeneration through them by co-transplantation with bone-marrow-derived mesenchymal stem cells: Case series of 14 patients

“…A fourth unresolved issue is whether to obtain stem cells from patients with spinal cord injury or from healthy volunteers. 58 Our choice for using autologous mesenchymal stem cells obtained from the iliac crest has been based on the overwhelming experimental evidence [59][60][61][62] in support of the efficacy of mesenchymal stem cells. They are more easily obtained from various tissues such as the bone marrow and adipose tissue 63 ; they have been reported to stimulate neurite outgrowth over neural proteoglycans, myelin-associated glycoprotein, and Nogo-A 64 ; they can differentiate both in vitro and in vivo into cells expressing neuronal markers.…”

Stem Cells and Neuronal Differentiation

“…In all treatment groups (differentiated, undifferentiated, and mix), there was less cavitation than lesion sites in the control group. The Basso-BeattieBresnahan (BBB) score was significantly higher in rats transplanted with a combination of cells and in rats transplanted with neural-induced MSCs alone than in undifferentiated and control rats [218]. Put together, the data obtained from the in vivo transplantation of MSCs in rodent models and clinical trials suggests that MSCs can promote endogenous reparative mechanisms that may prove applicable and beneficial for neurodegenerative disease treatment.…”