Abstract
To obtain insights into the cardiomyogenic potential of hematopoietic tissue, we intravenously (i.v.) injected purified hematopoietic stem/progenitor cells into newborn recipients that may fully potentiate the developmental plasticity of stem cells. Transplantation of mouse bone marrow (BM) lineage antigen-negative (Lin-) cells resulted in the generation of the cells that displayed cardiomyocyte-specific antigenic profiles and contractile function when transplanted into syngeneic newborn recipients. To clarify the mechanism underlying the cardiomyogenic potential, green fluorescent protein (GFP)-labeled BM Lin-ScaI+ hematopoietic progenitors were transplanted into neonatal mice constitutively expressing cyan fluorescence protein (CFP). Lambda image acquisition and linear unmixing analysis using confocal microscopy successfully separated GFP and CFP, and revealed that donor GFP+ cardiomyocytes coexpressed host-derived CFP. We further reconstituted human hemopoietic- and immune systems in mice by injecting human cord blood (CB)-derived Lin-CD34+CD38- hematopoietic stem cells (HSCs) into neonatal T cell-B cell -NK cell- immune-deficient NOD/SCID/IL2rγ null mice. Fluoroescence in situ hybridization analysis of recipient cardiac tissues demonstrated that human and murine chromosomes were colocalized in the same cardiomyocytes, indicating that cell fusion occurred between human hematopoietic progeny and mouse cardiomyocytes. These syngeneic- and xenogeneic neonatal transplantations provide compelling evidence that hematopoietic stem/progenitor cells contribute to the postnatal generation of cardiomyocytes through cell fusion, not through transdifferentiation.
| Original language | English |
|---|---|
| Journal | FASEB Journal |
| Volume | 20 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jan 1 2006 |
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All Science Journal Classification (ASJC) codes
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics
Cite this
Purified human hematopoietic stem cells contribute to the generation of cardiomyocytes through cell fusion. / Ishikawa, Fumihiko; Shimazu, Hideki; Shultz, Leonard D.; Fukata, Mitsuhiro; Nakamura, Ryu; Lyons, Bonnie; Shimoda, Kazuya; Shimoda, Shinji; Kanemaru, Takaaki; Nakamura, Kei Ichiro; Ito, Hiroyuki; Kaji, Yoshikazu; Perry, Anthony C.F.; Harada, Mine.
In: FASEB Journal, Vol. 20, No. 7, 01.01.2006.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Purified human hematopoietic stem cells contribute to the generation of cardiomyocytes through cell fusion
AU - Ishikawa, Fumihiko
AU - Shimazu, Hideki
AU - Shultz, Leonard D.
AU - Fukata, Mitsuhiro
AU - Nakamura, Ryu
AU - Lyons, Bonnie
AU - Shimoda, Kazuya
AU - Shimoda, Shinji
AU - Kanemaru, Takaaki
AU - Nakamura, Kei Ichiro
AU - Ito, Hiroyuki
AU - Kaji, Yoshikazu
AU - Perry, Anthony C.F.
AU - Harada, Mine
PY - 2006/1/1
Y1 - 2006/1/1
N2 - To obtain insights into the cardiomyogenic potential of hematopoietic tissue, we intravenously (i.v.) injected purified hematopoietic stem/progenitor cells into newborn recipients that may fully potentiate the developmental plasticity of stem cells. Transplantation of mouse bone marrow (BM) lineage antigen-negative (Lin-) cells resulted in the generation of the cells that displayed cardiomyocyte-specific antigenic profiles and contractile function when transplanted into syngeneic newborn recipients. To clarify the mechanism underlying the cardiomyogenic potential, green fluorescent protein (GFP)-labeled BM Lin-ScaI+ hematopoietic progenitors were transplanted into neonatal mice constitutively expressing cyan fluorescence protein (CFP). Lambda image acquisition and linear unmixing analysis using confocal microscopy successfully separated GFP and CFP, and revealed that donor GFP+ cardiomyocytes coexpressed host-derived CFP. We further reconstituted human hemopoietic- and immune systems in mice by injecting human cord blood (CB)-derived Lin-CD34+CD38- hematopoietic stem cells (HSCs) into neonatal T cell-B cell -NK cell- immune-deficient NOD/SCID/IL2rγ null mice. Fluoroescence in situ hybridization analysis of recipient cardiac tissues demonstrated that human and murine chromosomes were colocalized in the same cardiomyocytes, indicating that cell fusion occurred between human hematopoietic progeny and mouse cardiomyocytes. These syngeneic- and xenogeneic neonatal transplantations provide compelling evidence that hematopoietic stem/progenitor cells contribute to the postnatal generation of cardiomyocytes through cell fusion, not through transdifferentiation.
AB - To obtain insights into the cardiomyogenic potential of hematopoietic tissue, we intravenously (i.v.) injected purified hematopoietic stem/progenitor cells into newborn recipients that may fully potentiate the developmental plasticity of stem cells. Transplantation of mouse bone marrow (BM) lineage antigen-negative (Lin-) cells resulted in the generation of the cells that displayed cardiomyocyte-specific antigenic profiles and contractile function when transplanted into syngeneic newborn recipients. To clarify the mechanism underlying the cardiomyogenic potential, green fluorescent protein (GFP)-labeled BM Lin-ScaI+ hematopoietic progenitors were transplanted into neonatal mice constitutively expressing cyan fluorescence protein (CFP). Lambda image acquisition and linear unmixing analysis using confocal microscopy successfully separated GFP and CFP, and revealed that donor GFP+ cardiomyocytes coexpressed host-derived CFP. We further reconstituted human hemopoietic- and immune systems in mice by injecting human cord blood (CB)-derived Lin-CD34+CD38- hematopoietic stem cells (HSCs) into neonatal T cell-B cell -NK cell- immune-deficient NOD/SCID/IL2rγ null mice. Fluoroescence in situ hybridization analysis of recipient cardiac tissues demonstrated that human and murine chromosomes were colocalized in the same cardiomyocytes, indicating that cell fusion occurred between human hematopoietic progeny and mouse cardiomyocytes. These syngeneic- and xenogeneic neonatal transplantations provide compelling evidence that hematopoietic stem/progenitor cells contribute to the postnatal generation of cardiomyocytes through cell fusion, not through transdifferentiation.
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U2 - 10.1096/fj.05-4863fje
DO - 10.1096/fj.05-4863fje
M3 - Article
VL - 20
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 7
ER -