Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada.
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Cells. 2020 Dec 31;10(1):49. doi: 10.3390/cells10010049.
The clinical application of induced pluripotent stem cells (iPSC) needs to balance the use of an autologous source that would be a perfect match for the patient against any safety or efficacy issues that might arise with using cells from an older patient or donor. Drs. Takahashi and Yamanaka and the Office of Cellular and Tissue-based Products (PMDA), Japan, have had concerns over the existence of accumulated DNA mutations in the cells of older donors and the possibility of long-term negative effects. To mitigate the risk, they have chosen to partner with the Umbilical Cord (UC) banks in Japan to source allogeneic-matched donor cells. Production of iPSCs from UC blood cells (UCB) has been successful; however, reprogramming blood cells requires cell enrichment with columns or flow cytometry and specialized growth media. These requirements add to the cost of production and increase the manipulation of the cells, which complicates the regulatory approval process. Alternatively, umbilical cord tissue mesenchymal stromal cells (CT-MSCs) have the same advantage as UCB cells of being a source of young donor cells. Crucially, CT-MSCs are easier and less expensive to harvest and grow compared to UCB cells. Here, we demonstrate that CT-MSCs can be easily isolated without expensive enzymatic treatment or columns and reprogramed well using episomal vectors, which allow for the removal of the reprogramming factors after a few passages. Together the data indicates that CT-MSCs are a viable source of donor cells for the production of clinical-grade, patient matched iPSCs.
诱导多能干细胞（iPSC）的临床应用需要平衡使用与患者完美匹配的自体来源与使用老年患者或供体来源的细胞可能出现的任何安全性或疗效问题。Takahashi 博士和 Yamanaka 博士以及日本细胞和组织产品办公室（PMDA）一直担心老年供体细胞中存在累积的 DNA 突变以及长期负面效应的可能性。为了降低风险，他们选择与日本脐带血库合作，获取同种异体匹配的供体细胞。从脐带血细胞（UCB）中成功生产 iPSC；然而，重编程血细胞需要使用柱子或流式细胞术进行细胞富集和专门的生长培养基。这些要求增加了生产成本并增加了细胞操作，从而使监管批准过程复杂化。或者，脐带组织间充质基质细胞（CT-MSCs）与 UCB 细胞一样，具有年轻供体细胞的优势。至关重要的是，与 UCB 细胞相比，CT-MSCs 更容易且更便宜地收获和生长。在这里，我们证明 CT-MSCs 可以在没有昂贵的酶处理或柱子的情况下轻松分离，并使用可去除重编程因子的 episomal 载体很好地进行重编程，在经过几轮传代后可以去除重编程因子。这些数据表明 CT-MSCs 是生产临床级、患者匹配的 iPSC 的可行供体细胞来源。
