第3回 KEY Forum stem cell traits and developmental systems
タイトル；Mesenchymal stem cells derived from human induced pluripotent stem cells via mesoderm and neuroepithelium have different features and therapeutic potentials.
発表者；江藤 真哉 氏
（熊本大学 発生医学研究所 幹細胞誘導分野）
Mesenchymal stem cells (MSCs) isolated from adult human tissues is capable of proliferating in vitro with keeping their multipotency, and can be utilized for the regenerative medicine. However, their availability of self-renewal and multipotencyare limited and the procedures harvesting MSCs from bone marrow or adipose tissues are sometimes invasive. Therefore, it is eager to establish the novel methods or another sources to generate the MSCs extensively and safely.Induced pluripotent stem cells (iPSCs) can serve as an alternative cell source for these MSCs. Several studies have been dedicated to establishing induction methods from human iPSCs (hiPSCs) to MSCs.The previousstudiesonly compared their therapeutic effectson disease models with bone marrow-derived MSCs. This study established the definitive methods for differentiation of hiPSCs into MSCs via mesoderm and neuroepithelium. We adopted two steps for the differentiation to MSCs from iPSCs. At first, we generated PDGDR-α+/KDR- cells, which are MSC progenitor cells, purified by using flow cytometry after mesodermal and neuroepithelial differentiation. Next, the sorted PDGDR-α+/KDR- cells were differentiated into MSCs. Both MSCs exhibited self-renewal and multipotencyabilities and therapeutic potentials for skin wounds, pressure ulcers and osteoarthritis mouse models. In addition, The treatment with iPS derived MSC via mesoderm was more effective on the skin wound healing and osteoarthritis models than vianeuroepithelial. In contrast, the treatment with iPS derived MSC via neuroepithelialmore effectively cured the pressure ulcer model than via mesoderm. These results suggest that the therapeutic potential of MSCs is dependent on their origin. We need to find the proper MSCs fitting each disease in order to achieve the best therapeutic effect.
1) Sakurai H, Era T, Jakt LM, Okada M, NakaiS, Nishikawa S and Nishikawa S. In Vitro Modeling of Paraxial and Lateral Mesoderm Differentiation Reveals Early Reversibility. Stem Cells. 24 (3): 575-586.
2) Takashima Y, Era T, Nakano K, Kondo S, Kasuga M and Smith AG, Nishikawa S.Neuroepithelial cells supply an initial transient wave of MSC differentiation. Cell 129: 1377-1388.
3) Sakurai H, Sakaguchi Y, Shoji E, Nishino T, Maki I, Sakai H, Hanaoka K, Kakizuka A, and Sehara-Fujisawa A. In vitro modeling of paraxial mesodermal progenitors derived from induced pluripotent stem cells :Plos one. 7(10):e47078.