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Synergistic Effects of Bone Mesenchymal Stem Cells and Chondroitinase ABC on Nerve Regeneration After Acellular Nerve Allograft in Rats

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Abstract

This study aimed to evaluate whether combination therapy of bone marrow stromal cells (BMSCs) transplantation and chondroitinase ABC (ChABC) treatment further enhances axonal regeneration and functional recovery after acellular nerve allograft repair of the sciatic nerve gap in rats. Eight Sprague–Dawley rats were used as nerve donors, and 32 Wistar rats were randomly divided into four groups: Group I: acellular rat sciatic nerve (ARSN) group; Group II: ChABC treatment; Group III: BMSCs transplantation; and Group IV: ChABC treatment and BMSCs transplantation. The results showed that compared with ARSN control group, BMSC transplantation promoted axonal regeneration, the secretion of neural trophic factors NGF, BDNF and axon angiogenesis in nerve graft. ChABC treatment degraded chondroitin sulfate proteoglycans in ARSN in vitro and in vivo and improved BMSCs survival in ARSN. The combination therapy caused much better beneficial effects evidenced by increasing sciatic function index, nerve conduction velocity, restoration rate of tibialis anterior wet muscle weight, and myelinated nerve number, but did not further boost the therapeutic effects on neurotrophic factor production, axon angiogenesis, and sensory functional recovery by BMSC transplantation. Taken together, for the first time, we demonstrate the synergistic effects of BMSC transplantation and BMSCs treatment on peripheral nerve regeneration, and our findings may help establish novel strategies for cell transplantation therapy for peripheral nerve injury.

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Correspondence to Xiao-Jie Tong.

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10571_2011_9764_MOESM1_ESM.jpg

Sup Fig. 1 Detection of motor end plate in tibial muscles. Eight weeks after surgery, the tibial muscles in groups I–IV (A–D) were subjected to ACE staining. The quantitative analysis of IOD was shown in (E). Shown were representative images (n = 6). Bar: 50 μm. (JPEG 3632 kb)

10571_2011_9764_MOESM2_ESM.jpg

Sup Fig. 2 Detection of HRP retrograde tracing. Eight weeks after surgery, positive sensory neurons in L3–6 ganglio from groups I to IV (A–D) were labeled brown. The quantitative analysis of IOD was shown in (E). Shown were representative images (n = 6). Bar: 20 μm. (JPEG 4460 kb)

10571_2011_9764_MOESM3_ESM.jpg

Sup Fig. 3 Immunohistochemical staining of VEGF and CD34 in ARSN in different groups. Eight weeks after surgery, ARSN in groups I–IV was subjected to IHC with antibody against VEGF (A–D, groups I–IV, respectively) and CD34 (E–H, groups I–IV, respectively). The quantitative analysis of IOD was shown in (I). *P < 0.05 vs. group I (n = 6). Bar: 50 μm. (JPEG 1068 kb)

10571_2011_9764_MOESM4_ESM.jpg

Sup Fig. 4 Immunohistochemical staining of NGF and BDNF in ARSN in different groups. Eight weeks after surgery, ARSN in groups I–IV was subjected to IHC with antibody against NGF (A–D, group I–IV, respectively) and BDNF (E–H, group I–IV, respectively). The quantitative analysis of IOD was shown in (I). *P < 0.05 vs. groupI(n = 6). Bar: 50 μm. (JPEG 1044 kb)

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Wang, Y., Jia, H., Li, WY. et al. Synergistic Effects of Bone Mesenchymal Stem Cells and Chondroitinase ABC on Nerve Regeneration After Acellular Nerve Allograft in Rats. Cell Mol Neurobiol 32, 361–371 (2012). https://doi.org/10.1007/s10571-011-9764-4

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