title: Recellularized nerve allografts with differentiated mesenchymal stem cells promote peripheral nerve regeneration.
abstract: Chemical-extracted acellular nerve allografting, containing the natural nerve structure and elementary nerve extracellular matrix (ECM), has been used for peripheral nerve-defect treatment experimentally and clinically. However, functional outcome with acellular nerve allografting decreases with increased size of gap in nerve defects. Cell-based therapy is a good strategy for repairing long nerve defects. Bone-marrow-derived mesenchymal stem cells (BMSCs) and adipose-derived mesenchymal stem cells (ADSCs) can be induced to differentiate into cells with Schwann cell-like properties (BMSC-SCs or ADSC-SCs), which have myelin-forming ability in vitro and secrete trophic nerve growth factors. Here, we aimed to determine whether BMSC-SCs or ADSC-SCs are a promising cell type for enriching acellular grafts in nerve repair. We evaluated axonal regeneration distance by immunofluorescence staining after 2-week implantation. We used functional and histomorphometric analysis to evaluate 3-month regeneration of the novel cell-supplemented tissue-engineered nerve graft used to bridge a 15-mm-long sciatic nerve gap in rats. Introducing BMSC-SCs or ADSC-SCs to the acellular nerve graft promoted sciatic nerve regeneration and functional recovery. Nerve regeneration with BMSC-SCs or ADSC-SCs was comparable to that with autografting and Schwann cells alone and better than that with acellular nerve allografting alone. Differentiated bone-marrow-or adipose-derived MSCs may be a promising cell source for tissue-engineered nerve grafts and promote functional recovery after peripheral nerve injury.
authors.affiliation: Institute of Orthopedics, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing 100853, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhao
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Ren
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Jifeng
authors.initials: J
authors.lastname: Chen
authors.forename: Wenjing
authors.initials: W
authors.lastname: Xu
authors.forename: Shibi
authors.initials: S
authors.lastname: Lu
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.forename: Jiang
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology; D012584:Sciatic Nerve / Q000293:injuries* / Q000637:transplantation; D014182:Transplantation, Autologous