Abstract 19065: Circulating Cells Contribute to Post-infarction Myocardial Repair by Adopting Mature Cardiomyocyte and Endothelial Cell Fates
Objective: Whether bone marrow derived circulating cells engraft in ischemic myocardium and adopt non-hematopoietic fates remains controversial. Discordance may result from limitations of parabiosis models for fate tracking. Using a bone marrow chimera model, we hypothesized that circulating cells do, in fact, contribute to mature vessel formation and myocardial regeneration.
Methods: Recipient C57BL/6 (n=16) or C57BL/6-GFP mice (n=13) were lethally irradiated (10 Gy) and transplanted with 5x106 whole bone marrow cells from C57BL/6-DsRed donors. Four weeks post transplant, animals underwent acute myocardial infarction (MI) by ligation of the left anterior descending artery. Hearts were explanted 3 weeks post MI and were examined histologically. Individual cells were sorted after Langendorff isolation with FACS (Fig 1A).
Results: Bone marrow transplant reproducibly yielded >90% chimerism in peripheral blood and in the hematopoietic stem cell population. The majority of DsRed+ circulating cells adopted mature hematopoietic fates in ischemic myocardium, of which 82.3±1.54% were CD11b monocytes. However, DsRed+ circulating cells directly contributed to mature vessel formation, incorporating as cells expressing the endothelial markers, CD31 and von Willebrand factor (Fig 1B). In fact, 1.85±0.36% of the isolated CD31+ cells expressed DsRed. Fate tracking also demonstrated that circulating cells facilitate myocardial regeneration (Fig 1C) through cell fusion with native cardiomyocytes (0.03±0.01%), and to a lesser extent through transdifferentiation (0.00043±0.00029%).
Conclusions: Bone marrow derived circulating cells engraft in the ischemic heart and directly repair myocardium by adopting mature endothelial and cardiomyocyte fates. Mechanistic insight into the endogenous governance of circulating cell transdifferentiation and fusion post MI is essential to realizing the full potential of cytokine and progenitor cell based therapies.
Author Disclosures: C.E. Burnett: None. A.B. Goldstone: None. J.E. Cohen: None. J.B. Patel: None. B.E. Edwards: None. A. Eskandari: None. S. Ong: None. J.W. MacArthur: None. J.A. Shizuru: None. J. Woo: None.
- © 2015 by American Heart Association, Inc.