title: Study of synergistic role of allogenic skin-derived precursor differentiated Schwann cells and heregulin-1β in nerve regeneration with an acellular nerve allograft.
abstract: Development of tissue structure and three-dimensional microenvironment is crucial for regeneration of axons in the peripheral nerve repair. In this study we aimed to evaluate the efficacy of nerve regeneration by using an acellular nerve allograft (ANA) injected with allogenic skin-derived precursor differentiated Schwann cells (SKP-SCs) and heregulin-1β. Skin-derived precursor cells (SKPs) were generated from dermis of newborn (postnatal day 2) Wistar rats. In a rat model, nerve regeneration was determined across a 15 mm lesion in the sciatic nerve by using an ANA injected with allogenic SKP-SCs and heregulin-1β. The electrophysiological analysis, histological examination and electron microscopy were involved in this study. Cultured SKPs expressed nestin and fibronectin, and differentiated into cells with phenotype of SCs that presented characteristic markers of p75NGFR and S100-β. Implantation of SKP-SCs into the rat models by using ANA and allogenic skin-derived precursor differentiated Schwann cells (SKP-SCs) increases sciatic nerve functional index (SFI), peak amplitudes, nerve conduction velocities, number of myelinated fibers within the graft, while reduces incubation period, sciatic nerve injury-induced weight and contractions loss. Using ANA injected with SKP-SCs combined with heregulin-1β greatly promote peripheral nerve repair in a rat model. Our results suggest that SKP-SCs transplantation with heregulin-1β represents a powerful therapeutic approach, and facilitates the efficacy of acellular nerve allograft in peripheral nerve injury, though the detailed mechanism remains to be elucidated.
authors.affiliation: Department of Orthopedics, Jinshan Hospital of Fudan University, Shanghai, China.
authors.forename: Houlei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Jinshan Hospital of Fudan University, Shanghai, China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Jinshan Hospital of Fudan University, Shanghai, China.
authors.forename: Xinchao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Jinshan Hospital of Fudan University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Orthopedics, Jinshan Hospital of Fudan University, Shanghai, China. Electronic address: qingminzeng1703@163.com.
authors.forename: Qingmin
authors.initials: Q
authors.lastname: Zeng
mesh_terms: D064591:Allografts / Q000187:drug effects / Q000502:physiology / Q000637:transplantation; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D009416:Nerve Regeneration / Q000502:physiology*; D020890:Neuregulin-1 / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012583:Schwann Cells / Q000187:drug effects / Q000502:physiology* / Q000637:transplantation*; D016038:Skin Transplantation / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D020890:Neuregulin-1; C087230:heregulin beta1
keywords: Acellular nerve allograft (ANA); Neuregulin/heregulin-1β; Peripheral nerve repair; SKP; SKP-SCs