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Can the life span of human marrow stromal cells be prolonged by bmi‐1, E6, E7, and/or telomerase without affecting cardiomyogenic differentiation?
Author(s) -
Takeda Yukiji,
Mori Taisuke,
Imabayashi Hideaki,
Kiyono Tohru,
Gojo Satoshi,
Miyoshi Shunichirou,
Hida Naoko,
Ita Makoto,
Segawa Kaoru,
Ogawa Satoshi,
Sakamoto Michiie,
Nakamura Shinobu,
Umezawa Akihiro
Publication year - 2004
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.583
Subject(s) - mesenchymal stem cell , telomerase , microbiology and biotechnology , transplantation , biology , telomerase reverse transcriptase , population , stem cell , telomere , cellular differentiation , stromal cell , immunology , medicine , cancer research , genetics , gene , environmental health
Background Cell transplantation has recently been challenged to improve cardiac function of severe heart failure. Human mesenchymal stem cells (hMSCs) are multipotent cells that can be isolated from adult marrow stroma, but because of their limited life span, it is difficult to study them further. To overcome this problem, we attempted to prolong the life span of hMSCs and investigate whether the hMSCs modified with cell‐cycle‐associated genes can differentiate into cardiomyocytes in vitro . Methods We attempted to prolong the life span of hMSCs by infecting retrovirus encoding bmi‐1, human papillomavirus E6 and E7, and/or human telomerase reverse transcriptase genes. To determine whether the hMSCs with an extended life span could differentiate into cardiomyocytes, 5‐azacytidine‐treated hMSCs were co‐cultured with fetal cardiomyocytes in vitro . Result The established hMSCs proliferated over 150 population doublings. On day 3 of co‐cultivation, the hMSCs became elongated, like myotubes, began spontaneously beating, and acquired automaticity. Their rhythm clearly differed from that of the surrounding fetal mouse cardiomyocytes. The number of beating cardiomyocytes increased until 3 weeks. hMSCs clearly exhibited differentiated cardiomyocyte phenotypes in vitro as revealed by immunocytochemistry, RT‐PCR, and action potential recording. Conclusions The life span of hMSCs was prolonged without interfering with cardiomyogenic differentiation. hMSCs with an extended life span can be used to produce a good experimental model of cardiac cell transplantation and may serve as a highly useful cell source for cardiomyocytic transplantation. Copyright © 2004 John Wiley & Sons, Ltd.