The New York Stem Cell Foundation Research Institute, 619 West 54th Street, New York, NY, 10019, USA.
Stem Cell Res Ther. 2019 Jan 11;10(1):11. doi: 10.1186/s13287-018-1119-3.
Human mesenchymal stem cells are a strong candidate for cell therapies owing to their regenerative potential, paracrine regulatory effects, and immunomodulatory activity. Yet, their scarcity, limited expansion potential, and age-associated functional decline restrict the ability to consistently manufacture large numbers of safe and therapeutically effective mesenchymal stem cells for routine clinical applications. To overcome these limitations and advance stem cell treatments using mesenchymal stem cells, researchers have recently derived mesenchymal progenitors from human-induced pluripotent stem cells. Human-induced pluripotent stem cell-derived progenitors resemble adult mesenchymal stem cells in morphology, global gene expression, surface antigen profile, and multi-differentiation potential, but unlike adult mesenchymal stem cells, it can be produced in large numbers for every patient. For therapeutic applications, however, human-induced pluripotent stem cell-derived progenitors must be produced without animal-derived components (xeno-free) and in accordance with Good Manufacturing Practice guidelines.
In the present study we investigate the effects of expanding mesodermal progenitor cells derived from two human-induced pluripotent stem cell lines in xeno-free medium supplemented with human platelet lysates and in a commercial high-performance Good Manufacturing Practice-compatible medium (Unison Medium).
The results show that long-term culture in xeno-free and Good Manufacturing Practice-compatible media somewhat affects the morphology, expansion potential, gene expression, and cytokine profile of human-induced pluripotent stem cell-derived progenitors but supports cell viability and maintenance of a mesenchymal phenotype equally well as medium supplemented with fetal bovine serum.
The findings support the potential to manufacture large numbers of clinical-grade human-induced pluripotent stem cell-derived mesenchymal progenitors for applications in personalized regenerative medicine.
由于人类间充质干细胞具有再生潜能、旁分泌调节作用和免疫调节活性，因此它们是细胞治疗的强有力候选者。然而，其数量稀少、扩增潜力有限以及与年龄相关的功能下降限制了常规临床应用中持续制造大量安全且治疗有效的间充质干细胞的能力。为了克服这些限制并推进使用间充质干细胞的干细胞治疗，研究人员最近从人诱导多能干细胞中衍生出间充质祖细胞。人诱导多能干细胞衍生的祖细胞在形态、整体基因表达、表面抗原谱和多向分化潜能上与成人间充质干细胞相似，但与成人间充质干细胞不同的是，它可以为每位患者大量生产。然而，对于治疗应用而言，人诱导多能干细胞衍生的祖细胞必须在无动物源性成分（无动物源）的情况下生产，并符合良好生产规范指南。
在本研究中，我们研究了在补充有人血小板裂解物的无动物源培养基和商业高性能符合良好生产规范的培养基（Unison Medium）中扩大从两种人诱导多能干细胞系中衍生的中胚层祖细胞的效果。
结果表明，无动物源和符合良好生产规范的培养基中长期培养在一定程度上影响了人诱导多能干细胞衍生祖细胞的形态、扩增潜力、基因表达和细胞因子谱，但与补充胎牛血清的培养基一样，能够支持细胞活力和间充质表型的维持。
这些发现支持了制造大量临床级别的人诱导多能干细胞衍生的间充质祖细胞用于个性化再生医学应用的潜力。
