Chow Lyndah, Johnson Valerie, Regan Dan, Wheat William, Webb Saiphone, Koch Peter, Dow Steven
Center for Immune and Regenerative Medicine, Department of Clinical Sciences, College of Veterinary Medicine, Colorado State University, Ft. Collins, CO, United States.
Center for Immune and Regenerative Medicine, Department of Clinical Sciences, College of Veterinary Medicine, Colorado State University, Ft. Collins, CO, United States; Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine, Colorado State University, Ft. Collins, CO, United States.
Stem Cell Res. 2017 Dec;25:221-232. doi: 10.1016/j.scr.2017.11.010. Epub 2017 Nov 14.
Mesenchymal stem cells (MSCs) exhibit broad immune modulatory activity in vivo and can suppress T cell proliferation and dendritic cell activation in vitro. Currently, most MSC for clinical usage are derived from younger donors, due to ease of procurement and to the superior immune modulatory activity. However, the use of MSC from multiple unrelated donors makes it difficult to standardize study results and compare outcomes between different clinical trials. One solution is the use of MSC derived from induced pluripotent stem cells (iPSC); as iPSC-derived MSC have nearly unlimited proliferative potential and exhibit in vitro phenotypic stability. Given the value of dogs as a spontaneous disease model for pre-clinical evaluation of stem cell therapeutics, we investigated the functional properties of canine iPSC-derived MSC (iMSC), including immune modulatory properties and potential for teratoma formation. We found that canine iMSC downregulated expression of pluripotency genes and appeared morphologically similar to conventional MSC. Importantly, iMSC retained a stable phenotype after multiple passages, did not form teratomas in immune deficient mice, and did not induce tumor formation in dogs following systemic injection. We concluded therefore that iMSC were phenotypically stable, immunologically potent, safe with respect to tumor formation, and represented an important new source of cells for therapeutic modulation of inflammatory disorders.
间充质干细胞（MSCs）在体内表现出广泛的免疫调节活性，并且在体外能够抑制T细胞增殖和树突状细胞活化。目前，由于易于获取且具有卓越的免疫调节活性，大多数用于临床的MSCs来源于年轻供体。然而，使用来自多个无关供体的MSCs使得标准化研究结果以及比较不同临床试验的结果变得困难。一种解决方案是使用源自诱导多能干细胞（iPSC）的MSCs；因为源自iPSC的MSCs具有几乎无限的增殖潜力并且在体外表现出表型稳定性。鉴于犬作为干细胞治疗临床前评估的自发性疾病模型的价值，我们研究了犬iPSC衍生的MSCs（iMSCs）的功能特性，包括免疫调节特性和形成畸胎瘤的可能性。我们发现犬iMSCs下调了多能性基因的表达，并且在形态上与传统MSCs相似。重要的是，iMSCs在多次传代后保持稳定的表型，在免疫缺陷小鼠中不形成畸胎瘤，并且在全身注射后在犬中不诱导肿瘤形成。因此，我们得出结论，iMSCs在表型上是稳定的，具有免疫活性，在肿瘤形成方面是安全的，并且代表了用于炎症性疾病治疗调节的重要新细胞来源。
