title: Calpain inhibitor attenuates ER stress-induced apoptosis in injured spinal cord after bone mesenchymal stem cells transplantation.
abstract: Bone marrow mesenchymal stem cells (BMSCs) therapy for tissue repair is limited by low survival of cells transplanted in the recipient sites after spinal cord injury (SCI). Here, we investigated the effects of a calpain inhibitor (MDL28170) on BMSCs survival by a rat model of spinal cord injury in vitro and in vivo. Conditioned medium from hypoxia injured VSC4.1 motor neurons (Hypoxia-CM) were collected to mimic the micro-environment of injured spinal cord. Tunicamycin was also applied to induce endoplasmic reticulum (ER) stress in BMSCs. The CCK-8 assay, LDH leakage assay and flow cytometer assay demonstrated that MDL28170 could enhance BMSCs survival in response to Hypoxia-CM and tunicamycin. Moreover, MDL28170 significantly enhanced GFP-positive BMSCs survival in vivo after transplantation into the contused spinal cord of SCI rats. The protective effects of MDL28170 on BMSCs survival may inhibit the activation of calpain and the downstream ER stress-induced apoptosis. The present results suggested for the first time that MDL28170 with BMSCs transplant helped to rescue cells in injured spinal cord by modulating the ER stress-induced apoptosis. The calpain inhibitor, MDL28170 may have the promising new strategies for promoting the survival of transplanted BMSCs on cell-based regenerative medicine.
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Zhejiang University, PR China. Electronic address: w78084897@gmail.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Basic Medicine Sciences, School of Medicine, Zhejiang University, PR China. Electronic address: 21318209@zju.edu.cn.
authors.forename: Dongling
authors.initials: D
authors.lastname: Shi
authors.affiliation: Core Facilities, School of Medicine, Zhejiang University, PR China. Electronic address: songxh@zju.edu.cn.
authors.forename: Xinghui
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Basic Medicine Sciences, School of Medicine, Zhejiang University, PR China. Electronic address: bchenyy@zju.edu.cn.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Basic Medicine Sciences, School of Medicine, Zhejiang University, PR China. Electronic address: wanglinlin@zju.edu.cn.
authors.forename: Linlin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Zhejiang University, PR China. Electronic address: zxm@zju.edu.cn.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000502:physiology; D006023:Glycoproteins / Q000494:pharmacology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000639:trends*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000628:therapy*
chemical_list: D006023:Glycoproteins; C039304:calpain inhibitors
keywords: Apoptosis; ER stress; MDL28170; Mesenchymal stem cell; Spinal cord injury