In vitro transdifferentiation of human peripheral blood mononuclear cells to photoreceptor-like cells

Biology Open

Toshiyuki Ishii¹  Makoto Kaneda¹  Akihiro Umezawa²  Masashi Toyoda³  Yasuji Ueda⁴  Yukari Komuta⁵  Kiyoko Miyamoto⁵  Yuko Seko⁵ 

[1] Department of Physiology, Nippon Medical School, Sendagi, Bunkyo, Tokyo 113-8602, Japan;Department of Reproductive Biology, Center for Regenerative Medicine, National Institute for Child Health and Development, Okura, Setagaya, Tokyo 157-8535, Japan;Department of Vascular Medicine, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan;ID Pharma Co. Ltd, Tsukuba, Ibaraki 300-2611, Japan;Visual Functions Section, Department of Rehabilitation for Sensory Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Saitama 359-8555, Japan;

关键词: Direct reprogramming;    Human peripheral blood mononuclear cell (PBMC);    Photoreceptor;    Retinitis pigmentosa;   

DOI  :  10.1242/bio.016477

来源: DOAJ

【 摘 要 】

Direct reprogramming is a promising, simple and low-cost approach to generate target cells from somatic cells without using induced pluripotent stem cells. Recently, peripheral blood mononuclear cells (PBMCs) have attracted considerable attention as a somatic cell source for reprogramming. As a cell source, PBMCs have an advantage over dermal fibroblasts with respect to the ease of collecting tissues. Based on our studies involving generation of photosensitive photoreceptor cells from human iris cells and human dermal fibroblasts by transduction of photoreceptor-related transcription factors via retrovirus vectors, we transduced these transcription factors into PBMCs via Sendai virus vectors. We found that retinal disease-related genes were efficiently detected in CRX-transduced cells, most of which are crucial to photoreceptor functions. In functional studies, a light-induced inward current was detected in some CRX-transduced cells. Moreover, by modification of the culture conditions including additional transduction of RAX1 and NEUROD1, we found a greater variety of retinal disease-related genes than that observed in CRX-transduced PBMCs. These data suggest that CRX acts as a master control gene for reprogramming PBMCs into photoreceptor-like cells and that our induced photoreceptor-like cells might contribute to individualized drug screening and disease modeling of inherited retinal degeneration.

【 授权许可】

Unknown