Intravenous transplantation of amnion-derived mesenchymal stem cells promotes functional recovery and alleviates intestinal dysfunction after spinal cord injury

PLoS One. 2022 Jul 8;17(7):e0270606. doi: 10.1371/journal.pone.0270606. eCollection 2022.

Abstract

Spinal cord injury (SCI) is often accompanied by gastrointestinal dysfunction due to the disconnection of the spinal autonomic nervous system. Gastrointestinal dysfunction reportedly upregulates intestinal permeability, leading to bacterial translocation of the gut microbiome to the systemic circulation, which further activates systemic inflammation, exacerbating neuronal damage. Mesenchymal stem cells (MSC) reportedly ameliorate SCI. Here, we aimed to investigate their effect on the associated gastrointestinal dysfunction. Human amnion-derived MSC (AMSCs) were intravenously transplanted one day after a rat model of midthoracic SCI. Biodistribution of transplanted cells, behavioral assessment, and histological evaluations of the spinal cord and intestine were conducted to elucidate the therapeutic effect of AMSCs. Bacterial translocation of the gut microbiome was examined by in situ hybridization and bacterial culture of the liver. Systemic inflammations were examined by blood cytokines, infiltrating immune cells in the spinal cord, and the size of the peripheral immune tissue. AMSCs released various neurotrophic factors and were mainly distributed in the liver and lung after transplantation. AMSC-transplanted animals showed smaller spinal damage and better neurological recovery with preserved neuronal tract. AMSCs transplantation ameliorated intestinal dysfunction both morphologically and functionally, which prevented translocation of the gut microbiome to the systemic circulation. Systemic inflammations were decreased in animals receiving AMSCs in the chronic phase. Intravenous AMSC administration during the acute phase of SCI rescues both spinal damage and intestinal dysfunction. Reducing bacterial translocation may contribute to decreasing systemic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amnion
  • Animals
  • Gastrointestinal Diseases* / pathology
  • Inflammation / pathology
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Spinal Cord / pathology
  • Spinal Cord Injuries*
  • Tissue Distribution

Grants and funding

This study was supported by the Japan Agency for Medical Research and Development (AMED) [Grant Number JP17bk0104045] (MK, KH)and the Japan Society for the Promotion of Science Fujita Memorial Fund for Medical Research (MK).