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Published on: January 7, 2019
Circulating cells contribute to cardiomyocyte regeneration after injury
Jasmine M F Wu1, Ying-Chang Hsueh1, Hui-Ju Ch'ang1
1From the Institute of Basic Medical Sciences (J.M.F.W., Y.-C.H.) and Institute of Molecular Medicine (L.-W.W.), College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Surgery (C.-Y.L.) and Department of Radiation Oncology (H.-J.C.), National Cheng Kung University Hospital, Tainan, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan (H.-J.C.); Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan (H.N.); and Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (P.C. H.H.).
Insights
Circulating hematopoietic cells can regenerate heart muscle after injury. These cells fuse with or transform into cardiac cells, contributing to myocardial repair in a developed circulatory system.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Hematology
Background:
- Bone marrow hematopoietic cells contribute to ischemic myocardium.
- Previous studies showed no myocardial regeneration from hematopoietic cells.
- Early injury-induced signaling may confound prior findings.
Purpose of the Study:
- Re-evaluate the role of circulating cells in injured myocardium.
- Investigate cardiomyocyte regeneration mechanisms.
Main Methods:
- Pulse-chase labeling combined with a parabiosis model.
- Genetic fate mapping in mice.
- Analysis of cell fusion and transdifferentiation.
Main Results:
- Circulating cells from parabionts expressed cardiac-specific markers in injured myocardium.
- Hematopoietic cells acquired cardiac cell fate.
- Evidence of cell fusion and transdifferentiation observed.
Conclusions:
- Circulating cells participate in cardiomyocyte regeneration.
- This occurs in a mouse parabiosis model with a fully developed circulatory system before injury.
- Suggests a potential mechanism for myocardial repair.
Rationale:
The contribution of bone marrow-borne hematopoietic cells to the ischemic myocardium has been documented. However, a pivotal study reported no evidence of myocardial regeneration from hematopoietic-derived cells. The study did not take into account the possible effect of early injury-induced signaling as the test mice were parabiotically paired to partners immediately after surgery-induced myocardial injury when cross-circulation has not yet developed.
Objective:
To re-evaluate the role of circulating cells in the injured myocardium.
Methods And Results:
By combining pulse-chase labeling and parabiosis model, we show that circulating cells derived from the parabiont expressed cardiac-specific markers in the injured myocardium. Genetic fate mapping also revealed that circulating hematopoietic cells acquired cardiac cell fate by means of cell fusion and transdifferentiation.
Conclusions:
These results suggest that circulating cells participate in cardiomyocyte regeneration in a mouse model of parabiosis when the circulatory system is fully developed before surgery-induced heart injury.
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