Autocrine fibronectin from differentiating mesenchymal stem cells induces the neurite elongationin vitroand promotes nerve fiber regeneration in transected spinal cord injury

Abstract

Extracellular matrix (ECM) expression is temporally and spatially regulated during the development of stem cells. We reported previously that fibronectin (FN) secreted by bone marrow mesenchymal stem cells (MSCs) was deposited on the surface of gelatin sponge (GS) soon after culture. In this study, we aimed to assess the function of accumulated FN on neuronal differentiating MSCs as induced by Schwann cells (SCs) in three dimensional transwell co‐culture system. The expression pattern and amount of FN of differentiating MSCs was examined by immunofluorescence, Western blot and immunoelectron microscopy. The results showed that FN accumulated inside GS scaffold, although its mRNA expression in MSCs was progressively decreased during neural induction. MSC‐derived neuron‐like cells showed spindle‐shaped cell body and long extending processes on FN‐decorated scaffold surface. However, after blocking of FN function by application of monoclonal antibodies, neuron‐like cells showed flattened cell body with short and thick neurites, together with decreased expression of integrin β1. In vivo transplantation study revealed that autocrine FN significantly facilitated endogenous nerve fiber regeneration in spinal cord transection model. Taken together, the present results showed that FN secreted by MSCs in the early stage accumulated on the GS scaffold and promoted the neurite elongation of neuronal differentiating MSCs as well as nerve fiber regeneration after spinal cord injury. This suggests that autocrine FN has a dynamic influence on MSCs in a three dimensional culture system and its potential application for treatment of traumatic spinal cord injury. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1902–1911, 2016.

Differentiation of Human Mesenchymal Stem Cells from Wharton’s Jelly Towards Neural Stem Cells Using a Feasible and Repeatable Protocol

“…Fibronectin is a crucial component of the extracellular matrix (ECM) and is involved in epithelial-mesenchymal transition [74]. Moreover, MSCs can secrete fibronectin [75] promoting neurite elongation of MSCs after neural induction [76]. The obtained qRT-PCR results of hWJ-NSCs were compared to undifferentiated cells (hWJ-MSCs).…”

Potential of mesenchymal stem cells alone, or in combination, to treat traumatic brain injury

“…MSC‐derived exosomes have also been tested in porcine model of TBI coupled with hemorrhagic shock; consistent with the rodent data, the pigs had fewer cognitive deficits as determined with a neurological severity score and recovered faster than nontreated pigs . There is also evidence for MSC inducing immune suppression and anti‐inflammation; stimulating neurogenesis and angiogenesis; activating survival pathways and inhibiting apoptotic pathways; and enhancing neuroplasticity through neurite outgrowth and synaptogenesis …”

Prerequisites for Mesenchymal Stem Cell Transplantation in Spinal Cord Injury

“…It has been suggested that the combined use of tenascincytotactin, nerve growth factor /brain-derived neurotrophic factor/retinoic acid and human bone marrow-derived multipotent progenitor cells offers a new feasible method for nerve repair [134]. Fibronectin secreted by mesenchymal stem cells in the early stage has been found to accumulate on gelatin sponge scaffolds and promote neurite elongation of neuronal differentiating mesenchymal stem cells as well as nerve fiber regeneration after spinal cord injury [135].…”