Publication: Regeneration of heart muscle tissue: quantification of chimeric cardiomyocytes
and endothelial cells following transplantation
Authors
Thiele, J. ; Varus, E. ; Wickenhauser, C. ; Kvasnicka, H.M. ; Metz, K.A. ; Beelen, D.W.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Persuasive evidence has been recently
provided that adult bone marrow (BM) cells exert
greater plasticity than previously assumed. This review
is focused on the quantification of mixed chimerism
(mCh) in the hearts (cardiomyocytes and endothelial
cells) of patients after orthotopic heart to heart
transplantation (HHT) in comparison to full
(unmanipulated) allogeneic BM and peripheral blood
stem cell (PBSC) transplants. Following a sexmismatched
transplantation constellation heart muscle
tissue obtained at autopsy was examined. Evaluation of
mCh was most often performed by immunophenotyping
combined with fluorescence in-situ hybridization (FISH)
applying x- and y-chromosome-specific DNA probes.
When comparing our data with the results of former
studies that were regularly based on the detection of the
y-chromosome alone, the quantity of chimeric
cardiomyocytes after HHT ranged from 0% to 9%. On
the other hand, after full BM transplantats (chimeric)
cardiomyocytes of donor-type origin appeared at an
incidence between 0.23% to 6.4%. These disturbing
inconsistencies were assumed to be related to
methodology: the restriction to the y-chromosome,
disregard of the plane of section (detection sensitivity
ranging between 35% and 67%) and state of tissue
preservation (cadaver hearts). Therefore, when strictly
applying dual color FISH and limiting the recognition of
chimeric cardiomyocytes and endothelial cells to the
presence of two distinctive signals detection sensitivity was significantly enhanced. Contrasting a total
congruence with the genotyping in control specimens of
normal cadaver hearts, a striking disparity in the extent
of mCh was found depending on the different modes of
transplantation. After allografting with PBSC a
considerably low incidence (1.6%) of chimeric
cardiomyocytes was determined contrasting with 5.3% of donor-derived cells after full BM transplants.
Following HHT host-type endothelial cells (16.2 %) of
the intramural and subepicardial vessel walls were more
often encountered than following BM and PBSC
allografting. These findings are in keeping with the
assumption of a sprouting and migration of vascular
structures into the donor heart from the site of surgical
aligment and injury between retained host and donor
atrial walls. When considering the other methods of
transplantation (BM, PBSC) the data on chimeric
endothelial cells support the hypothesis of a common
hemangioblast. Concerning the cardiomyocytes it seems
most reasonable to assume that primitive mesenchymal
stem cells of the BM play a pivotal role in the
development of mCh. This phenomenon is more
extensively expressed than previously expected and may
be related to an enforced repair of the damaged
myocardium during the post-transplant period as the
sequel of myeloablative (cardiotoxic) conditioning .
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