Netrin-1 overexpression in bone marrow mesenchymal stem cells promotes functional recovery in a rat model of peripheral nerve injury

Abstract

Transplantation of bone marrow mesenchymal stem cells (BMSCs) has been developed as a new method of treating diseases of the peripheral nervous system. While netrin-1 is a critical molecule for axonal path finding and nerve growth, it may also affect vascular network formation. Here, we investigated the effect of transplanting BMSCs that produce netrin-1 in a rat model of sciatic nerve crush injury. We introduced a sciatic nerve crush injury, and then injected 1×106 BMSCs infected by a recombinant adenovirus expressing netrin-1 Ad5-Netrin-1-EGFP or culture medium into the injured part in the next day. At day 7, 14 and 28 after injection, we measured motor nerve conduction and detected mRNA expressions of netrin-1 receptors UNC5B and Deleted in Colorectal Cancer (DCC), and neurotrophic factors brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) by real-time PCR. We also detected protein expressions of BDNF and NGF by Western blotting assays and examined BMSCs that incorporated into myelin and vascellum. The results showed that BMSCs infected by Ad5-Netrin-1-EGFP significantly improved the function of the sciatic nerve, and led to increased expression of BDNF and NGF (P<0.05). Moreover, 28 days after injury, more Schwann cells were found in BMSCs infected by Ad5-Netrin-1-EGFP compared to control BMSCs. In conclusion, transplantation of BMSCs that produce netrin-1 improved the function of the sciatic nerve after injury. This method may be a new treatment of nerve injury.

Role of Netrin-1 Signaling in Nerve Regeneration

“…However, the low dose effect of exogenous Netrin-1 has not been tested yet. A more recent report showed that transplanting Netrin-1 overexpressing bone marrow mesenchymal stem cells to the injury site of rat sciatic nerve promotes axon regeneration and functional recovery [106]. Thus, the DCC and Unc5B knockdown data together with the data from Netrin-1 overexpressing stem cells suggests that Netrin-1 signaling promotes in vivo peripheral nerve regeneration.…”

Association of genetic variants in lncRNAH19with risk of colorectal cancer in a Chinese population

“…As we known, the abnormality of gene expression may increase the risk or severity of diseases [ 11 – 13 ]. Long noncoding RNAs (lncRNAs) have also been implicated in the crucial functions of various biological process involved in cancer susceptibility [ 14 , 15 ].…”

The Differentiation Stage of Transplanted Stem Cells Modulates Nerve Regeneration

“…It has been reported that transplantation of rat bone marrow mesenchymal stem cells (BMSCs) in a rat sciatic nerve injury model leads to the increased expression of BDNF and NGF at the injured site 43 . To investigate whether the engrafted iPSC-derived NCSCs and Schwann cells secrete neurotrophic factors (NFs) and participate in paracrine signaling in nerve regeneration, ELISA analyses of human neurotrophic factors NGF, BDNF, and CNTF were performed in the tissues within the implanted nerve conduits.…”