A Study Of Intravenous Transplanted Stem Cells Improve Function In Peripheral Nerve Injury

Objective To evaluate the effect of different times after peripheral nerve injury onthe capacity of RFP-MSCs (red fluorescence protein bone marrow mesenchymal stemcells, RFP-BMSCs) homing and study the function of bone marrow mesenchymal stemcells on the repair of peripheral nerve crush injury.MethodObservation of peripheral nerve Wallerian degeneration induces stem cellsmigration:72adult male Sprague-Dawley rats,weight220-250g,were randomly dividedinto6groups (n=12)according to the weight. SD rats in each group were further dividedinto two groups (Group A and Group B) according to the injected cell and drug. RatsinGroup A were injected RFP-BMSCs and saline via tail vein, Rats in Group B wereinjected RFP-BMSCs and AMD3100.All the experimental rats were cut off sciatic nerveunder aseptic conditions,proximal ligation and diatal exclusion. After sciatic nervetransaction1d,3d,7d,14d,4w,8w, rats were injected RFP-BMSCs and saline (group A) orRFP-BMSCs and AMD3100(group B) via tail vein, and3days after injection, alltreated rats were subjected to in vivo imaging system observation.Intravenous injected stem cells enhance repair of peripheral nerve injury: theoperation of sciatic nerve5mm length crush injury were conducted, then theexperimental animals were divided into three groups: saline group,1x106RFP-BMSCsgroup,5x106RFP-BMSCs group. One week after peripheral nerve crush injury modelestablishment, experimental animals were intravenous transplanted5X106stem cells(5X106RFP-BMSCs),1X106stem cells (106RFP-BMSCs)or saline (saline group) viatail vein. Then after injection, in vivoimaging&analysis system, sciatic nerve functionindex (SFI) measurement, electrophysiological test and neuromuscular pathology wereused to evaluate the homing of stem cells and its effect on the repair of peripheral nervecrush injury. Results1In Wallerian degeneration sciatic nerve, RFP-BMSCs aggregation ability firstincreased and then decreased with time. During early Wallerian degeneration of sciaticnerve(1d~3d), RFP-BMSCs aggregation ability in group B (RFP-BMSCs andAMD3100) was significantly weaker than in group A (RFP-BMSCs and saline).2In vivoimaging&analysis system showed that distalWallerian degenerationregionand proximal region of crush injury segment in1X106RFP-BMSCs group and5X106RFP-BMSCs group expressed high intensity fluorescent signal accumulation; theintensity of fluorescent signal in5X106RFP-BMSCs group was higher than in106RFP-BMSCs group. SFI measurements confirmed that the motor function recovered asearly as two weeks after surgery, and in2,4,6three time point, the recovery of5X106RFP-BMSCs group was better than saline group and1X106RFP-BMSCs group.Similarly,electrophysiological testing and neuromuscular pathology indicated that theeffect of crush injury recovery in5X106RFP-BMSCs group was better than othergroups.Conclusion1The RFP-BMSCs’ ability of homing to peripheral nerve injury was first increasedand then decreased. The homing phenomenon may be partly regulated bySDF-1-CXCR4signaling pathway, and can be inhibited by CXCR4specific antagonistAMD3100. Therefore, enhance repair of peripheral nerve injury through intravenousstem cells injection is not only a feasible method.2Intravenous transplantationBMSCs can successfully migrated to distal Walleriandegeneration regionand proximal region of crush injury segment, and promoted therepair of damaged nerve. Because of the effect of pulmonary capillary retention, theeffects of5X106RFP-BMSCs group was better than other groups, which has importantsignificance to guide the use of intravenous transplantation of stem cells.