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

Ke X, Li Q, Xu L, Zhang Y, Li D, Ma J, Mao X - J Biomed Res (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Affiliated Hospital of Jiangsu University , Zhenjiang, Jiangsu 212001 , China .

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 1×10(6) 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.

No MeSH data available.


Related in: MedlinePlus

Protein levels of neurotrophic factors change after nerve injury.Expression of BDNF (A) and NGF (B) protein at d7, d14 and d28 after surgery. Representative Western blot of protein with β-actin used as an internal control from nerve treated with control medium, Null-BMSCs, and Netrin-1-BMSCs. Values are means±SD of data from 6 separate samples. *P<0.05.
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f05: Protein levels of neurotrophic factors change after nerve injury.Expression of BDNF (A) and NGF (B) protein at d7, d14 and d28 after surgery. Representative Western blot of protein with β-actin used as an internal control from nerve treated with control medium, Null-BMSCs, and Netrin-1-BMSCs. Values are means±SD of data from 6 separate samples. *P<0.05.

Mentions: In injured nerves, BDNF and NGF protein levels changed similarly to the time-course of mRNA changes. The highest level of BDNF was observed at day 7 and 14 for NGF. There were significant differences among the groups (all P<0.05). At day 28, the protein levels decreased and approached normal levels, with no significant differences among the groups (all P>0.05). BDNF level in the BMSC/Netrin-1 group had significant difference at day 7, 14 and 28. In the BMSC group, and there was a significant difference between day 28 and day 7 or day 14 (P<0.05), but no significant difference was found between day 7 and day 14 (P>0.05). NGF level in the BMSC/Netrin-1and BMSCs groups had significant difference among day 7, 14 and 28. BDNF and NGF levels in the control group have no significant difference among day 7, 14 and 28 (all P>0.05, Fig. 5A-B).


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

Ke X, Li Q, Xu L, Zhang Y, Li D, Ma J, Mao X - J Biomed Res (2015)

Protein levels of neurotrophic factors change after nerve injury.Expression of BDNF (A) and NGF (B) protein at d7, d14 and d28 after surgery. Representative Western blot of protein with β-actin used as an internal control from nerve treated with control medium, Null-BMSCs, and Netrin-1-BMSCs. Values are means±SD of data from 6 separate samples. *P<0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4585432&req=5

f05: Protein levels of neurotrophic factors change after nerve injury.Expression of BDNF (A) and NGF (B) protein at d7, d14 and d28 after surgery. Representative Western blot of protein with β-actin used as an internal control from nerve treated with control medium, Null-BMSCs, and Netrin-1-BMSCs. Values are means±SD of data from 6 separate samples. *P<0.05.
Mentions: In injured nerves, BDNF and NGF protein levels changed similarly to the time-course of mRNA changes. The highest level of BDNF was observed at day 7 and 14 for NGF. There were significant differences among the groups (all P<0.05). At day 28, the protein levels decreased and approached normal levels, with no significant differences among the groups (all P>0.05). BDNF level in the BMSC/Netrin-1 group had significant difference at day 7, 14 and 28. In the BMSC group, and there was a significant difference between day 28 and day 7 or day 14 (P<0.05), but no significant difference was found between day 7 and day 14 (P>0.05). NGF level in the BMSC/Netrin-1and BMSCs groups had significant difference among day 7, 14 and 28. BDNF and NGF levels in the control group have no significant difference among day 7, 14 and 28 (all P>0.05, Fig. 5A-B).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Affiliated Hospital of Jiangsu University , Zhenjiang, Jiangsu 212001 , China .

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 1×10(6) 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.

No MeSH data available.


Related in: MedlinePlus