Zhang Xiaohong, Soda Yasushi, Takahashi Kenji, Bai Yuansong, Mitsuru Ayako, Igura Koichi, Satoh Hitoshi, Yamaguchi Satoru, Tani Kenzaburo, Tojo Arinobu, Takahashi Tsuneo A
Division of Cell Processing, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Biochem Biophys Res Commun. 2006 Dec 29;351(4):853-9. doi: 10.1016/j.bbrc.2006.10.125. Epub 2006 Nov 2.
We reported previously that mesenchymal progenitor cells derived from chorionic villi of the human placenta could differentiate into osteoblasts, adipocytes, and chondrocytes under proper induction conditions and that these cells should be useful for allogeneic regenerative medicine, including cartilage tissue engineering. However, similar to human mesenchymal stem cells (hMSCs), though these placental cells can be isolated easily, they are difficult to study in detail because of their limited life span in vitro. To overcome this problem, we attempted to prolong the life span of human placenta-derived mesenchymal cells (hPDMCs) by modifying hTERT and Bmi-1, and investigated whether these modified hPDMCs retained their differentiation capability and multipotency. Our results indicated that the combination of hTERT and Bmi-1 was highly efficient in prolonging the life span of hPDMCs with differentiation capability to osteogenic, adipogenic, and chondrogenic cells in vitro. Clonal cell lines with directional differentiation ability were established from the immortalized parental hPDMC/hTERT+Bmi-1. Interestingly, hPDMC/Bmi-1 showed extended proliferation after long-term growth arrest and telomerase was activated in the immortal hPDMC/Bmi-1 cells. However, the differentiation potential was lost in these cells. This study reports a method to extend the life span of hPDMCs with hTERT and Bmi-1 that should become a useful tool for the study of mesenchymal stem cells.
我们先前报道，源自人胎盘绒毛膜的间充质祖细胞在适当的诱导条件下可分化为成骨细胞、脂肪细胞和软骨细胞，并且这些细胞应可用于包括软骨组织工程在内的同种异体再生医学。然而，与人间充质干细胞（hMSCs）类似，尽管这些胎盘细胞易于分离，但由于它们在体外的寿命有限，很难对其进行详细研究。为克服这一问题，我们尝试通过修饰hTERT和Bmi-1来延长人胎盘来源间充质细胞（hPDMCs）的寿命，并研究这些修饰后的hPDMCs是否保留其分化能力和多能性。我们的结果表明，hTERT和Bmi-1的组合在延长hPDMCs的寿命方面非常有效，且这些细胞在体外具有向成骨细胞、脂肪细胞和软骨细胞分化的能力。从永生化的亲代hPDMC/hTERT+Bmi-1建立了具有定向分化能力的克隆细胞系。有趣的是，hPDMC/Bmi-1在长期生长停滞后显示出增殖延长，并且端粒酶在永生化的hPDMC/Bmi-1细胞中被激活。然而，这些细胞失去了分化潜能。本研究报道了一种用hTERT和Bmi-1延长hPDMCs寿命的方法，该方法应成为研究间充质干细胞的有用工具。
