Transplantation of a tissue-engineered human vascularized cardiac muscle

Ayelet Lesman, Manhal Habib, Oren Caspi, Amira Gepstein, Gil Arbel, Shulamit Levenberg*, Lior Gepstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Myocardial regeneration strategies have been hampered by the lack of sources for human cardiomyocytes (CMs) and by the significant donor cell loss following transplantation. We assessed the ability of a three-dimensional tissue-engineered human vascularized cardiac muscle to engraft in the in vivo rat heart and to promote functional vascularization. Human embryonic stem cell-derived CMs alone or with human endothelial cells (human umbilical vein endothelial cells) and embryonic fibroblasts (triculture constructs) were seeded onto biodegradable porous scaffolds. The resulting tissue constructs were transplanted to the in vivo rat heart and formed cardiac tissue grafts. Immunostaining studies for human-specific CD31 and α-smooth muscle actin demonstrated the formation of both donor (human) and host (rat)-derived vasculature within the engrafted triculture tissue constructs. Intraventricular injection of fluorescent microspheres or lectin resulted in their incorporation by human-derived vessels, confirming their functional integration with host coronary vasculature. Finally, the number of blood vessels was significantly greater in the triculture tissue constructs (60.3±8/mm3, p<0.05) when compared with scaffolds containing only CMs (39.0±14.4/ mm3). In conclusion, a tissue-engineered human vascularized cardiac muscle can be established ex vivo and transplanted in vivo to form stable grafts. By utilizing a multicellular preparation we were able to increase biograft vascularization and to show that the preexisting human vessels can become functional and contribute to tissue perfusion.

Original languageEnglish
Pages (from-to)115-125
Number of pages11
JournalTissue Engineering - Part A.
Issue number1
StatePublished - 1 Jan 2010
Externally publishedYes


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