Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 833-845 |
| Number of pages | 13 |
| Journal | Journal of Gene Medicine |
| Volume | 6 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2004 Aug |
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Keywords
- Bmi-1
- Cardiomyocytes
- Immortalization
- Marrow stroma
- Papillomavirus
- Senescence
ASJC Scopus subject areas
- Genetics
Cite this
Can the life span of human marrow stromal cells be prolonged by bmi-1, E6, E7, and/or telomerase without affecting cardiomyogenic differentiation? / 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.
In: Journal of Gene Medicine, Vol. 6, No. 8, 08.2004, p. 833-845.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Can the life span of human marrow stromal cells be prolonged by bmi-1, E6, E7, and/or telomerase without affecting cardiomyogenic differentiation?
AU - Takeda, Yukiji
AU - Mori, Taisuke
AU - Imabayashi, Hideaki
AU - Kiyono, Tohru
AU - Gojo, Satoshi
AU - Miyoshi, Shunichirou
AU - Hida, Naoko
AU - Ita, Makoto
AU - Segawa, Kaoru
AU - Ogawa, Satoshi
AU - Sakamoto, Michiie
AU - Nakamura, Shinobu
AU - Umezawa, Akihiro
PY - 2004/8
Y1 - 2004/8
N2 - 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.
AB - 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.
KW - Bmi-1
KW - Cardiomyocytes
KW - Immortalization
KW - Marrow stroma
KW - Papillomavirus
KW - Senescence
UR - http://www.scopus.com/inward/record.url?scp=4344577481&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4344577481&partnerID=8YFLogxK
U2 - 10.1002/jgm.583
DO - 10.1002/jgm.583
M3 - Article
C2 - 15293342
AN - SCOPUS:4344577481
VL - 6
SP - 833
EP - 845
JO - Journal of Gene Medicine
JF - Journal of Gene Medicine
SN - 1099-498X
IS - 8
ER -