Kinoshita Kahori, Kuno Shinichiro, Ishimine Hisako, Aoi Noriyuki, Mineda Kazuhide, Kato Harunosuke, Doi Kentaro, Kanayama Koji, Feng Jingwei, Mashiko Takanobu, Kurisaki Akira, Yoshimura Kotaro
Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan.
Department of Plastic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan
Stem Cells Transl Med. 2015 Feb;4(2):146-55. doi: 10.5966/sctm.2014-0181. Epub 2015 Jan 5.
Stage-specific embryonic antigen-3 (SSEA-3)-positive multipotent mesenchymal cells (multilineage differentiating stress-enduring [Muse] cells) were isolated from cultured human adipose tissue-derived stem/stromal cells (hASCs) and characterized, and their therapeutic potential for treating diabetic skin ulcers was evaluated. Cultured hASCs were separated using magnetic-activated cell sorting into positive and negative fractions, a SSEA-3+ cell-enriched fraction (Muse-rich) and the remaining fraction (Muse-poor). Muse-rich hASCs showed upregulated and downregulated pluripotency and cell proliferation genes, respectively, compared with Muse-poor hASCs. These cells also released higher amounts of certain growth factors, particularly under hypoxic conditions, compared with Muse-poor cells. Skin ulcers were generated in severe combined immunodeficiency (SCID) mice with type 1 diabetes, which showed delayed wound healing compared with nondiabetic SCID mice. Treatment with Muse-rich cells significantly accelerated wound healing compared with treatment with Muse-poor cells. Transplanted cells were integrated into the regenerated dermis as vascular endothelial cells and other cells. However, they were not detected in the surrounding intact regions. Thus, the selected population of ASCs has greater therapeutic effects to accelerate impaired wound healing associated with type 1 diabetes. These cells can be achieved in large amounts with minimal morbidity and could be a practical tool for a variety of stem cell-depleted or ischemic conditions of various organs and tissues.
从培养的人脂肪组织来源的干/基质细胞（hASCs）中分离并鉴定了阶段特异性胚胎抗原-3（SSEA-3）阳性的多能间充质细胞（多谱系分化应激耐受[Muse]细胞），并评估了它们治疗糖尿病皮肤溃疡的潜力。使用磁激活细胞分选将培养的hASCs分离为阳性和阴性部分，一个富含SSEA-3 +细胞的部分（富含Muse）和其余部分（贫Muse）。与贫Muse的hASCs相比，富含Muse的hASCs分别显示多能性和细胞增殖基因的上调和下调。与贫Muse细胞相比，这些细胞还释放出更高量的某些生长因子，特别是在缺氧条件下。在患有1型糖尿病的严重联合免疫缺陷（SCID）小鼠中产生皮肤溃疡，与非糖尿病SCID小鼠相比，其伤口愈合延迟。与用贫Muse细胞治疗相比，用富含Muse的细胞治疗显著加速了伤口愈合。移植的细胞作为血管内皮细胞和其他细胞整合到再生的真皮中。然而，在周围完整区域未检测到它们。因此，所选的ASC群体具有更大的治疗效果，可加速与1型糖尿病相关的受损伤口愈合。这些细胞可以大量获得，发病率极低，并且可能是用于各种器官和组织的多种干细胞耗竭或缺血状况的实用工具。
