Jasmine M F Wu1, Ying-Chang Hsueh1, Hui-Ju Ch'ang1, Chwan-Yau Luo1, Li-Wha Wu1, Hiromitsu Nakauchi1, Patrick C H Hsieh2. 1. From 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.). 2. From 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.). phsieh@ibms.sinica.edu.tw.
Abstract
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.
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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