A new immunodeficient Duchenne muscular dystrophy rat model to evaluate engraftment after human cell transplantation

Masae Sato; Megumi Goto; Keitaro Yamanouchi; Hidetoshi Sakurai

doi:10.3389/fphys.2023.1094359

A new immunodeficient Duchenne muscular dystrophy rat model to evaluate engraftment after human cell transplantation

Front Physiol. 2023 Apr 10:14:1094359. doi: 10.3389/fphys.2023.1094359. eCollection 2023.

Authors

Masae Sato¹, Megumi Goto¹, Keitaro Yamanouchi², Hidetoshi Sakurai¹

Affiliations

¹ Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
² Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked fatal muscular disease, affecting one in 3,500 live male births worldwide. Currently, there is no cure for this disease, except for steroid-based treatment to attenuate disease progression. Cell transplantation therapy is a promising therapeutic approach, however, there is a lack of appropriate animal models to conduct large-scale preclinical studies using human cells, including biochemical and functional tests. Here, we established an immunodeficient DMD rat model and performed exhaustive pathological analysis and transplantation efficiency evaluation to assess its suitability to study DMD. Our DMD rat model exhibited histopathological characteristics similar to those observed in human patients with DMD. Human myoblasts demonstrated successful engraftment following transplantation into these rats. Therefore, this immunodeficient DMD rat model would be useful in preclinical studies to develop cellular transplantation therapies for DMD.

Keywords: DMD; cell transplantation; immunodeficient; pathology; rat model.

Grants and funding

This work was primarily supported by a grant from the Acceleration Transformative Research for Medical Innovation Set-up Scheme (ACT-MS) (JP18im0210817) and partially by a grant from The Core Center for iPS Cell Research (JP13bm0104001), both of which are provided by the Japan Agency for Medical Research and Development, AMED (to HS).