Circulating cells contribute to cardiomyocyte regeneration after injury.
BACKGROUND
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.


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.
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.).
Jasmine M F
JM
Wu
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.).
Ying-Chang
YC
Hsueh
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.).
Hui-Ju
HJ
Ch'ang
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.).
Chwan-Yau
CY
Luo
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.).
Li-Wha
LW
Wu
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.).
Hiromitsu
H
Nakauchi
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.
Patrick C H
PC
Hsieh
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002459:Cell Fusion; D019070:Cell Lineage; D049109:Cell Proliferation; D058948:Cell Tracking / Q000379:methods; D054338:Cell Transdifferentiation; D004195:Disease Models, Animal; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D010227:Parabiosis; D012038:Regeneration; D013997:Time Factors
D015415:Biomarkers; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
blood circulation; cell fusion; cell transdifferentiation; parabiosis; regeneration; stem cells