Tan Xiaobing, Dai Qingli, Guo Tao, Xu Jingshu, Dai Qingyuan
Department of Cardiology and Endodontics, the First People's Hospital of Yunnan Province, Jinbi Road No. 157, Kunming, Yunnan, China; The Affiliated Hospital of Kunming University of Science and Technology, Jinbi Road No. 157, Kunming, Yunnan, China.
Department of Ultrasound, Dali Bai Autonomous Prefecture People's Hospital, Renminnan Road No. 35, Xiaguan, Dali, Yunnan, China.
Biochem Biophys Res Commun. 2018 Jan 22;495(4):2490-2497. doi: 10.1016/j.bbrc.2017.12.007. Epub 2017 Dec 5.
Advance in stem cell research resulted in several processes to generate induced pluripotent stem cells (iPSCs) from adult somatic cells. In our previous study, the reprogramming of iPSCs from human dental mesenchymal stem cells (MSCs) including SCAP and DPSCs, has been reported. Herein, safe iPSCs were reprogrammed from SCAP and DPSCs using non-integrating RNA virus vector, which is an RNA virus carrying no risk of altering host genome. DPSCs- and SCAP-derived iPSCs exhibited the characteristics of the classical morphology with human embryonic stem cells (hESCs) without integration of foreign genes, indicating the potential of their clinical application. Moreover, induced PSCs showed the capacity of self-renewal and differentiation into cardiac myocytes. We have achieved the differentiation of hiPSCs to cardiomyocytes lineage under serum and feeder-free conditions, using a chemically defined medium CDM3. In CDM3, hiPSCs differentiation is highly generating cardiomyocytes. The results showed this protocol produced contractile sheets of up to 97.2% TNNT2 cardiomyocytes after purification. Furthermore, derived hiPSCs differentiated to mature cells of the three embryonic germ layers in vivo and in vitro of beating cardiomyocytes. The above whole protocol enables the generation of large scale of highly pure cardiomyocytes as needed for cellular therapy.
干细胞研究的进展带来了多种从成体细胞生成诱导多能干细胞(iPSC)的方法。在我们之前的研究中,已经报道了从人牙间充质干细胞(MSC)包括SCAP和DPSC重编程iPSC的情况。在此,使用非整合RNA病毒载体从SCAP和DPSC重编程得到了安全的iPSC,该载体是一种不存在改变宿主基因组风险的RNA病毒。源自DPSC和SCAP的iPSC表现出与人类胚胎干细胞(hESC)相似的经典形态特征,且没有外源基因整合,表明了它们临床应用的潜力。此外,诱导多能干细胞表现出自我更新以及分化为心肌细胞的能力。我们使用化学限定培养基CDM3在无血清和无饲养层条件下实现了人诱导多能干细胞向心肌细胞谱系的分化。在CDM3中,人诱导多能干细胞高度分化为心肌细胞。结果表明,该方案在纯化后可产生高达97.2%的TNNT2心肌细胞的收缩片层。此外,衍生的人诱导多能干细胞在体内外均可分化为跳动心肌细胞的三个胚胎胚层的成熟细胞。上述整个方案能够根据细胞治疗的需要大规模生成高度纯净的心肌细胞。