人类绒毛膜绒毛间质干细胞是自体心脏干细胞治疗的细胞新来源
Human mesenchymal stem cell from human chorionic villi is a new cell source for autologous cardiac stem cell therapy.

Kazuma Okamoto， Naoko Hida， Shunichiro Miyoshi， Nobuhiro Nishiyama， Yukinori Ikegami， Daisuke Kami， Taro Uyama， Kenji Miyado， Kaoru Segawa， Hironori Asada， Yasunori Yoshimura， Ryo Aeba， Satoshi Ogawa， Akihiro Umezawa， Ryohei Yozu.

Ryohei Yozu　　Professor， Department of Surgery，Graduate School of Medicine，Keio University

　　

　　Background： Marrow-derived mesenchymal stem cell (MSC) is a cell source for cardiac stem cell therapy， however， those cells may not function well because of patient‘s disease background， age， and the ability of stem cell transdifferentiation that may be impaired.  Placental chorionic villi are a good cell source for MSC since the young and fresh MSC can be obtained from them without any ethical problem. We hypothesized that placental chorionic villi cells (CVCs) can transdifferentiate into physiologically functioning cardiomyocyte in vitro.

　　Methods and results： Human placental CVCs were isolated at male infant delivery， and confirmed them as infant-derived cells by sex chromosomal analysis (to exclude the contamination of maternal endometrial cells). Before cardiomyogenic induction， mRNA of Nkx-2.5， GATA-4， hBNP， and cardiac tropnonin-I (Trop-I) were detected by RT-PCR in the CVCs. The GFP-labeled CVCs were co-cultured with murine fetal cardiomyocyte to induce cardiomyogenic differentiation. A week after the induction， GFP-positive CVCs rhythmically and synchronously contracted， suggesting the presence　of electrical communication between CVCs.  The cardiomyocyte-specific action potential was obtained from spontaneous beating CVCs that showed the specific cardiac action potential plateau (duration； 209 +- 48 msec， amplitude 63.9 +- 8.4 mV， n=14). Immunocytochemical analysis with confocal laser microscopy revealed differentiated CVCs which were stained positive for anti-Trop-I， sarcomeric  -actinin (clearly stained striation pattern) and connexin 43 (diffused dot-like shapes at the margin of CVCs). The percentage of Trop-I positive cells in the GFP-positive cells was 14 +- 5%. The fractional shortening of the beating CVCs was 5.5 +- 0.4% (n=10).

　　Conclusions： In CVCs， MSC with cardiomyogenic ability accounted for 14%. Although CVCs are usually considered as medical waste at delivery， we can obtain young stem cells from them without any ethical problem. We can utilize our own CVCs to repair our own heart disease in the future if they are stored at birth. CVCs are superior to marrow-derived MSC because they can be obtained from younger people and have a higher cardiomyogenic potential.

　　Learning object 1： To determine whether human placental chorionic villi-derived mesenchymal stem cells have a potential to transdifferentiate into the physiologically functioning cardiomyocyte in vitro.