Partial cell fusion: a newly recognized type of communication between dedifferentiating cardiomyocytes and fibroblasts.
OBJECTIVE
Fibroblasts have been shown to couple to neonatal cardiomyocytes in heterocellular cultures through functional gap junctions. Our objective was to provide evidence for an additional type of heterocellular communication between fibroblasts and adult cardiomyocytes in vitro and in vivo.


METHODS
The contact areas in heterocellular co-cultures were evaluated by specific labeling and the intercellular communication was studied using preloading of fibroblasts with tracer molecules. Heterocellular fibroblast-cardiomyocyte contacts present in the in vitro setting and in the border zone of a rabbit myocardial infarction in vivo were further examined by electron microscopy.


RESULTS
Addition of fibroblasts preloaded with the fluorescent low molecular weight tracer calcein-AM to cultured myocytes indicated early dye transfer via connexin 43 functional gap junctions. At a later time-period after co-culturing, dye transfer of fibroblasts preloaded with the high molecular weight tracer dextran 10,000 suggested partial cell fusion. The membrane continuity giving rise to this partial cell fusion was confirmed by electron microscopy, clearly showing areas of intercytoplasmic contacts between fibroblasts and phenotypically adapted (dedifferentiated) cardiomyocytes. Fluorescein-labeled annexin V affinity studies revealed transient exposure of phosphatidylserine at the contact sites, suggesting that phosphatidylserine mediates the fusion process. Close contacts between cardiac fibroblasts and dedifferentiated cardiomyocytes accompanied by disruption of the basal lamina were observed in the border zone of a rabbit myocardial infarction in vivo.


CONCLUSIONS
Our results suggest that the partial cell fusion-type of heterocellular communication in our co-culture model and the contacts observed in vivo may lead to new insights in cardiovascular disease.
Driesen
Ronald B
RB
Department of Molecular Cell Biology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Dispersyn
Gerrit D
GD
Verheyen
Fons K
FK
van den Eijnde
Stefan M
SM
Hofstra
Leo
L
Thoné
Fred
F
Dijkstra
Petra
P
Debie
Wiel
W
Borgers
Marcel
M
Ramaekers
Frans C S
FC
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation; D002459:Cell Fusion; D002462:Cell Membrane / Q000648:ultrastructure; D018920:Coculture Techniques; D018031:Connexin 43 / Q000032:analysis; D003600:Cytosol / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology* / Q000648:ultrastructure; D017629:Gap Junctions / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008854:Microscopy, Electron; D018715:Microscopy, Video; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000648:ultrastructure; D011817:Rabbits
D018031:Connexin 43