Sato Masae, Goto Megumi, Yamanouchi Keitaro, Sakurai Hidetoshi
Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Front Physiol. 2023 Apr 10;14:1094359. doi: 10.3389/fphys.2023.1094359. eCollection 2023.
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.
杜氏肌营养不良症(DMD)是一种X连锁的致命性肌肉疾病,全球每3500例活产男婴中就有1例受影响。目前,除了使用类固醇治疗来减缓疾病进展外,尚无治愈该疾病的方法。细胞移植疗法是一种有前景的治疗方法,然而,缺乏合适的动物模型来使用人类细胞进行大规模临床前研究,包括生化和功能测试。在此,我们建立了一种免疫缺陷的DMD大鼠模型,并进行了详尽的病理分析和移植效率评估,以评估其用于研究DMD的适用性。我们的DMD大鼠模型表现出与人类DMD患者相似的组织病理学特征。人类成肌细胞移植到这些大鼠体内后显示出成功植入。因此,这种免疫缺陷的DMD大鼠模型将有助于开展临床前研究,以开发针对DMD的细胞移植疗法。