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Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle.

Matsuura K, Wada H, Nagai T, Iijima Y, Minamino T, Sano M, Akazawa H, Molkentin JD, Kasanuki H, Komuro I - J. Cell Biol. (2004)

Bottom Line: Furthermore, cardiomyocytes reentered the G2-M phase in the cell cycle after fusing with proliferative noncardiomyocytes.Transplanted endothelial cells or skeletal muscle-derived cells fused with adult cardiomyocytes in vivo.In the cryoinjured heart, there were Ki67-positive cells that expressed both cardiac and endothelial lineage marker proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.

ABSTRACT
The concept of the plasticity or transdifferentiation of adult stem cells has been challenged by the phenomenon of cell fusion. In this work, we examined whether neonatal cardiomyocytes fuse with various somatic cells including endothelial cells, cardiac fibroblasts, bone marrow cells, and endothelial progenitor cells spontaneously in vitro. When cardiomyocytes were cocultured with endothelial cells or cardiac fibroblasts, they fused and showed phenotypes of cardiomyocytes. Furthermore, cardiomyocytes reentered the G2-M phase in the cell cycle after fusing with proliferative noncardiomyocytes. Transplanted endothelial cells or skeletal muscle-derived cells fused with adult cardiomyocytes in vivo. In the cryoinjured heart, there were Ki67-positive cells that expressed both cardiac and endothelial lineage marker proteins. These results suggest that cardiomyocytes fuse with other cells and enter the cell cycle by maintaining their phenotypes.

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Neonatal rat cardiomyocytes expressed PH3 and cyclinB1 after cell fusion with HUVEC or cFB. Neonatal rat cardiomyocytes were cocultured with GFP+ HUVEC or GFP+ cFB and double stained with anti-cTnT (red) and anti-PH3 (blue) or anti-cyclinB1 (blue) antibodies. Fused cells between cardiomyocytes and HUVEC or cFB coexpressed both GFP and cTnT (a, c, e, and g, yellow in merged images), and expressed PH3 (b and d, blue) and cyclinB1 (f and h, blue) in their nuclei. Bars, 50 μm.
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fig5: Neonatal rat cardiomyocytes expressed PH3 and cyclinB1 after cell fusion with HUVEC or cFB. Neonatal rat cardiomyocytes were cocultured with GFP+ HUVEC or GFP+ cFB and double stained with anti-cTnT (red) and anti-PH3 (blue) or anti-cyclinB1 (blue) antibodies. Fused cells between cardiomyocytes and HUVEC or cFB coexpressed both GFP and cTnT (a, c, e, and g, yellow in merged images), and expressed PH3 (b and d, blue) and cyclinB1 (f and h, blue) in their nuclei. Bars, 50 μm.

Mentions: To determine whether cardiomyocytes reenter the cell cycle after fusion, we examined the expression of the cell cycle marker proteins such as Ki67, phosphohistone H3 (PH3), and cyclinB1 in fused cells. First, we examined whether monocultured HUVEC, cFB, and neonatal cardiomyocytes expressed Ki67, PH3, and cyclinB1 (Fig. 4). Many of HUVEC and cFB in the growth medium expressed Ki67, PH3, and cyclinB1 in their nuclei. Some neonatal rat cardiomyocytes expressed Ki67, but not PH3 and cyclinB1, suggesting that some neonatal cardiomyocytes are in the G1-S stage, but not in the G2-M stage of the cell cycle. However, when fused with HUVEC and cFB some cardiomyocytes expressed PH3 (Fig. 5 b for HUVEC and Fig. 5 d for cFB) and cyclinB1 (Fig. 5 f for HUVEC and Fig. 5 h for cFB). Among cardiomyocytes fused with HUVEC, ∼9% of the cells expressed PH3 (Fig. 6 A). When treated for 6 h with nocodazole, an inhibitor of microtubule dynamics and cell cycle progression (Blajeski et al., 2002; Tamamori-Adachi et al., 2003), the number of PH3-expressing fused cells was increased up to ∼21% in fused cells. At 3 h after the withdrawal of nocodazole, this number was decreased to ∼15%. In cardiomyocytes fused with cFB (Fig. 6 B), ∼14% of the cells expressed PH3, and at 24 h after the nocodazole treatment the number of PH3-expressing fused cells was increased up to ∼29%. This number was decreased to ∼20% at 3 h after the withdrawal of nocodazole. These results suggest that some cardiomyocytes reenter the stage of mitosis after fusion with HUVEC and cFB. Mitosis of fused cardiomyocytes was confirmed by the existence of cells that showed visible chromosomes characteristic of the several distinct phases of mitosis (Fig. 6 C). In Fig. 6, GFP+ cardiomyocytes fused with RFP+ HUVEC (b and j) or RFP+ cFB (f) show prophase chromosomes (c), metaphase chromosomes (g), and anaphase chromosomes (k).


Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle.

Matsuura K, Wada H, Nagai T, Iijima Y, Minamino T, Sano M, Akazawa H, Molkentin JD, Kasanuki H, Komuro I - J. Cell Biol. (2004)

Neonatal rat cardiomyocytes expressed PH3 and cyclinB1 after cell fusion with HUVEC or cFB. Neonatal rat cardiomyocytes were cocultured with GFP+ HUVEC or GFP+ cFB and double stained with anti-cTnT (red) and anti-PH3 (blue) or anti-cyclinB1 (blue) antibodies. Fused cells between cardiomyocytes and HUVEC or cFB coexpressed both GFP and cTnT (a, c, e, and g, yellow in merged images), and expressed PH3 (b and d, blue) and cyclinB1 (f and h, blue) in their nuclei. Bars, 50 μm.
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Related In: Results  -  Collection

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fig5: Neonatal rat cardiomyocytes expressed PH3 and cyclinB1 after cell fusion with HUVEC or cFB. Neonatal rat cardiomyocytes were cocultured with GFP+ HUVEC or GFP+ cFB and double stained with anti-cTnT (red) and anti-PH3 (blue) or anti-cyclinB1 (blue) antibodies. Fused cells between cardiomyocytes and HUVEC or cFB coexpressed both GFP and cTnT (a, c, e, and g, yellow in merged images), and expressed PH3 (b and d, blue) and cyclinB1 (f and h, blue) in their nuclei. Bars, 50 μm.
Mentions: To determine whether cardiomyocytes reenter the cell cycle after fusion, we examined the expression of the cell cycle marker proteins such as Ki67, phosphohistone H3 (PH3), and cyclinB1 in fused cells. First, we examined whether monocultured HUVEC, cFB, and neonatal cardiomyocytes expressed Ki67, PH3, and cyclinB1 (Fig. 4). Many of HUVEC and cFB in the growth medium expressed Ki67, PH3, and cyclinB1 in their nuclei. Some neonatal rat cardiomyocytes expressed Ki67, but not PH3 and cyclinB1, suggesting that some neonatal cardiomyocytes are in the G1-S stage, but not in the G2-M stage of the cell cycle. However, when fused with HUVEC and cFB some cardiomyocytes expressed PH3 (Fig. 5 b for HUVEC and Fig. 5 d for cFB) and cyclinB1 (Fig. 5 f for HUVEC and Fig. 5 h for cFB). Among cardiomyocytes fused with HUVEC, ∼9% of the cells expressed PH3 (Fig. 6 A). When treated for 6 h with nocodazole, an inhibitor of microtubule dynamics and cell cycle progression (Blajeski et al., 2002; Tamamori-Adachi et al., 2003), the number of PH3-expressing fused cells was increased up to ∼21% in fused cells. At 3 h after the withdrawal of nocodazole, this number was decreased to ∼15%. In cardiomyocytes fused with cFB (Fig. 6 B), ∼14% of the cells expressed PH3, and at 24 h after the nocodazole treatment the number of PH3-expressing fused cells was increased up to ∼29%. This number was decreased to ∼20% at 3 h after the withdrawal of nocodazole. These results suggest that some cardiomyocytes reenter the stage of mitosis after fusion with HUVEC and cFB. Mitosis of fused cardiomyocytes was confirmed by the existence of cells that showed visible chromosomes characteristic of the several distinct phases of mitosis (Fig. 6 C). In Fig. 6, GFP+ cardiomyocytes fused with RFP+ HUVEC (b and j) or RFP+ cFB (f) show prophase chromosomes (c), metaphase chromosomes (g), and anaphase chromosomes (k).

Bottom Line: Furthermore, cardiomyocytes reentered the G2-M phase in the cell cycle after fusing with proliferative noncardiomyocytes.Transplanted endothelial cells or skeletal muscle-derived cells fused with adult cardiomyocytes in vivo.In the cryoinjured heart, there were Ki67-positive cells that expressed both cardiac and endothelial lineage marker proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.

ABSTRACT
The concept of the plasticity or transdifferentiation of adult stem cells has been challenged by the phenomenon of cell fusion. In this work, we examined whether neonatal cardiomyocytes fuse with various somatic cells including endothelial cells, cardiac fibroblasts, bone marrow cells, and endothelial progenitor cells spontaneously in vitro. When cardiomyocytes were cocultured with endothelial cells or cardiac fibroblasts, they fused and showed phenotypes of cardiomyocytes. Furthermore, cardiomyocytes reentered the G2-M phase in the cell cycle after fusing with proliferative noncardiomyocytes. Transplanted endothelial cells or skeletal muscle-derived cells fused with adult cardiomyocytes in vivo. In the cryoinjured heart, there were Ki67-positive cells that expressed both cardiac and endothelial lineage marker proteins. These results suggest that cardiomyocytes fuse with other cells and enter the cell cycle by maintaining their phenotypes.

Show MeSH
Related in: MedlinePlus