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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

The function of the sciatic nerve was evaluated.A: Neurobehavioral evaluation. A representative illustration of the sciatic nerve function index (SFI) from day 7 to 28 after surgery in the three treatment groups is shown. B: The sketch map of SFI was shown.
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f02: The function of the sciatic nerve was evaluated.A: Neurobehavioral evaluation. A representative illustration of the sciatic nerve function index (SFI) from day 7 to 28 after surgery in the three treatment groups is shown. B: The sketch map of SFI was shown.

Mentions: One week after surgery, we found that the gait of rats in the 3 groups was unstable. The left limb was obviously pulled, and footprint was unclear. Thus, measurements were not exact, and data were not included in the statistical analysis. From 2 to 4 weeks, the function of the sciatic nerve recovered gradually. The recovery, as reflected by SFI changes, in the transplantation group was superior to that in the control group. At days 14 and 28, SFI was –23.69±3.17 and –15.45±3.19 in the BMSC/Netrin-1 group, respectively, which was higher than that in the BMSC (−33.81±0.74, −26.24±7.16) and control (−53.06±1.65, −40.98±1.96) groups (P<0.05). However, no significant differences were found between the BMSC/Netrin-1 (−35.49±4.30) and BMSC (−43.35±5.37) group at day 7 (P>0.05), although both groups were significantly different from the control group (−63.20±1.61, P<0.01). The SFI changes of each group were significantly different atday 7, 14 and 28 (all P<0.01, Fig. 2).


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)

The function of the sciatic nerve was evaluated.A: Neurobehavioral evaluation. A representative illustration of the sciatic nerve function index (SFI) from day 7 to 28 after surgery in the three treatment groups is shown. B: The sketch map of SFI was shown.
© Copyright Policy
Related In: Results  -  Collection

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

f02: The function of the sciatic nerve was evaluated.A: Neurobehavioral evaluation. A representative illustration of the sciatic nerve function index (SFI) from day 7 to 28 after surgery in the three treatment groups is shown. B: The sketch map of SFI was shown.
Mentions: One week after surgery, we found that the gait of rats in the 3 groups was unstable. The left limb was obviously pulled, and footprint was unclear. Thus, measurements were not exact, and data were not included in the statistical analysis. From 2 to 4 weeks, the function of the sciatic nerve recovered gradually. The recovery, as reflected by SFI changes, in the transplantation group was superior to that in the control group. At days 14 and 28, SFI was –23.69±3.17 and –15.45±3.19 in the BMSC/Netrin-1 group, respectively, which was higher than that in the BMSC (−33.81±0.74, −26.24±7.16) and control (−53.06±1.65, −40.98±1.96) groups (P<0.05). However, no significant differences were found between the BMSC/Netrin-1 (−35.49±4.30) and BMSC (−43.35±5.37) group at day 7 (P>0.05), although both groups were significantly different from the control group (−63.20±1.61, P<0.01). The SFI changes of each group were significantly different atday 7, 14 and 28 (all P<0.01, Fig. 2).

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