Journal Article

Adipose-Derived Mesenchymal Stromal Cell Transplantation for Severe Spinal Cord Injury: Functional Improvement Supported by Angiogenesis and Neuroprotection

Hideaki Nakajima, Akihiko Matsumine, Shuji Watanabe, Ai Takahashi, Arisa Kubota

2023

Overview

Mesenchymal stromal cell transplantation alone is insufficient when motor dysfunction is severe; combination therapy with rehabilitation could improve motor function. Here, we aimed to analyze the characteristics of adipose-derived MSCs (AD-MSCs) and determine their effectiveness in severe spinal cord injury (SCI) treatment. A severe SCI model was created and motor function were compared. The rats were divided into AD-MSC-transplanted treadmill exercise-combined (AD-Ex), AD-MSC-transplanted non-exercise (AD-noEx), PBS-injected exercise (PBS-Ex), and no PBS-injected exercise (PBS-noEx) groups. In cultured cell experiments, AD-MSCs were subjected to oxidative stress, and the effects on the extracellular secretion of AD-MSCs were investigated using multiplex flow cytometry. We assessed angiogenesis and macrophage accumulation in the acute phase. Spinal cavity or scar size and axonal preservation were assessed histologically in the subacute phase. Significant motor function improvement was observed in the AD-Ex group. Vascular endothelial growth factor and C-C motif chemokine 2 expression in AD-MSC culture supernatants increased under oxidative stress. Enhanced angiogenesis and decreased macrophage accumulation were observed at 2 weeks post-transplantation, whereas spinal cord cavity or scar size and axonal preservation were observed at 4 weeks. Overall, AD-MSC transplantation combined with treadmill exercise training improved motor function in severe SCI. AD-MSC transplantation promoted angiogenesis and neuroprotection.

• Publisher: MDPI AG,MDPI
• Subject: acute spinal cord injury / Adipose tissues / adipose-derived mesenchymal stromal cell transplantation / adipose-derived mesenchymal stromal cell transplantation; acute spinal cord injury; functional recovery; treadmill exercise training; oxidative stress / Angiogenesis / Animals / Antibodies / Body fat / Bone marrow / Care and treatment / Cell culture / Chemokines / Cicatrix / Cicatrix - pathology / Contusions / Cytology / Cytotoxicity / Experiments / Fitness equipment / Fitness training programs / Flow cytometry / functional recovery / Health aspects / Hypoxia / Laboratory animals / Macrophages / Mesenchymal Stem Cell Transplantation / Mesenchymal Stem Cells / Mesenchymal Stem Cells - metabolism / Neovascularization / Neuroprotection / Oxidative stress / Physical training / Preservation / QH573-671 / Rats / Rehabilitation / Spinal Cord Injuries / Spinal Cord Injuries - pathology / Stem cell transplantation / Stem cells / Transplantation / treadmill exercise training / Vascular endothelial growth factor / Vascular Endothelial Growth Factor A