De novo cardiomyocytes from within the activated adult heart after injury

被引：488

作者：

Smart, Nicola ^{[1
]}

Bollini, Sveva ^{[1
]}

Dube, Karina N. ^{[1
]}

Vieira, Joaquim M. ^{[1
]}

Zhou, Bin ^{[2
,3
,4
,5
]}

Davidson, Sean ^{[6
]}

Yellon, Derek ^{[6
]}

Riegler, Johannes ^{[7
,8
,9
]}

Price, Anthony N. ^{[10
]}

Lythgoe, Mark F. ^{[7
,8
]}

Pu, William T. ^{[2
,3
,4
]}

Riley, Paul R. ^{[1
]}

机构：

[1] UCL Inst Child Hlth, Mol Med Unit, London WC1N 1EH, England

[2] Childrens Hosp, Harvard Stem Cell Inst, Boston, MA 02115 USA

[3] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[5] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Beijing 20031, Peoples R China

[6] UCL, Hatter Cardiovasc Inst, London WC1E 6HX, England

[7] UCL, Dept Med, Ctr Adv Biomed Imaging CABI, London WC1E 6DD, England

[8] UCL, Inst Child Hlth, London WC1E 6DD, England

[9] UCL, Ctr Math & Phys Life Sci & Expt Biol CoMPLEX, London WC1E 6BT, England

[10] Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, Fac Med, London W12 0NN, England

来源：

NATURE | 2011年 / 474卷 / 7353期

基金：

英国工程与自然科学研究理事会;

关键词：

EPICARDIAL PROGENITORS; SMOOTH-MUSCLE; NEOVASCULARIZATION; LINEAGE; CELLS; TBX18;

D O I：

10.1038/nature10188

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A significant bottleneck in cardiovascular regenerative medicine is the identification of a viable source of stem/progenitor cells that could contribute new muscle after ischaemic heart disease and acute myocardial infarction(1). A therapeutic ideal-relative to cell transplantation-would be to stimulate a resident source, thus avoiding the caveats of limited graft survival, restricted homing to the site of injury and host immune rejection. Here we demonstrate in mice that the adult heart contains a resident stem or progenitor cell population, which has the potential to contribute bona fide terminally differentiated cardiomyocytes after myocardial infarction. We reveal a novel genetic label of the activated adult progenitors via re-expression of a key embryonic epicardial gene, Wilm's tumour 1 (Wt1), through priming by thymosin beta 4, a peptide previously shown to restore vascular potential to adult epicardium-derived progenitor cells(2) with injury. Cumulative evidence indicates an epicardial origin of the progenitor population, and embryonic reprogramming results in the mobilization of this population and concomitant differentiation to give rise to de novo cardiomyocytes. Cell transplantation confirmed a progenitor source and chromosome painting of labelled donor cells revealed transdifferentiation to a myocyte fate in the absence of cell fusion. Derived cardiomyocytes are shown here to structurally and functionally integrate with resident muscle; as such, stimulation of this adult progenitor pool represents a significant step towards resident-cell-based therapy in human ischaemic heart disease.

引用

页码：640 / U117

页数：7

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