In Vitro Differentiation of Bone Marrow Mesenchymal Stem Cells into Neuron-Like Cells by Cerebrospinal Fluid Improves Motor Function of Middle Cerebral Artery Occlusion Rats

Abstract

Bone marrow mesenchymal stem cells (BMSCs) represent a promising tool for stem cell-based therapies. However, the majority of BMSC transplants only allow for limited recovery of the lost functions. We previously found that human cerebrospinal fluid (hCSF) is more potent than growth factors in differentiating human BMSCs into neuron-like cells in vitro. In this study, we studied the effect of transplantation of rat BMSC-derived neuron-like cells (BMSC-Ns) induced by hCSF into rat brain with middle cerebral artery occlusion (MCAO). The survival and differentiation of the transplanted cells were determined using immunofluorescence staining of bromodeoxyuridine. The recovery of neurological function were observed by the modified neurological severity score (modified NSS) at 4, 15, and 32 days after cell transplantation, HE staining for determination of the infarct volume at day 32 after cell transplantation. Transplantation of BMSC-Ns or BMSCs significantly improved indexes of neurological function and reduced infarct size in rats previously subjected to MCAO compared with those in the control group. Remarkably, 32 days after transplantation, rats treated with BMSC-Ns presented a smaller infarct size, higher number of neuron-specific, enolase-positive, and BrdU-positive cells, and improved neurological function compared with BMSC group. Our results demonstrate that transplantation of hCSF-treated BMSC-Ns significantly improves neurological function and reduces infarct size in rats subjected to MCAO. This study may pave a new avenue for the treatment of MCAO.

Comparison of the neuronal differentiation abilities of bone marrow-derived and adipose tissue-derived mesenchymal stem cells

“…BMSCs and ADSCs are known to differentiate into neurons ( 22 , 23 ). In our study, nestin, a neural precursor stem cells marker, and β-tubulin III, an immature neuronal marker, were expressed in native BMSCs and ADSCs, which suggested that both MSCs retained a native potential for neuronal differentiation and were in conformity with other studies ( 20 ).…”

Differentiation of human adipose-derived stem cells into neuron/motoneuron-like cells for cell replacement therapy of spinal cord injury

“…Mesenchymal stem cells (MSCs) are a group of heterogeneous multipotent adult stem cells 22,23 can be differentiated into chondrocytes 24,25 , adipocytes 26 , myocytes 27,28 , endothelial cells 29,30 , and neurons 31–34 . The main advantages of adipose-derived stem cells (ADSCs), include the feasibility of autologous transplantation, the ability to secrete neurotrophic factors and cytokines to promote the survival of endogenous cells, and suppress the inflammatory response to facilitate tissue repair 17,35,36 .…”

Mesenchymal stromal cell secretome as a therapeutic strategy for traumatic brain injury

“…MSCs represent a powerful tool in the field of regenerative medicine. The results of in vitro studies showed that MSCs are capable of differentiating into neuron‐like cells . The therapeutic benefits of MSC transplantation have been reported in TBI animal models and clinical trial.…”

“…The results of in vitro studies showed that MSCs are capable of differentiating into neuron-like cells. 41,42 The therapeutic benefits of MSC transplantation have been reported in TBI animal models and clinical trial. MSCs isolated from bone marrow decreased blood-brain barrier permeability, inhibit activated microglia/macrophage accumulation in the thalamic region and promote neurogenesis in a rat model of TBI.…”