5-Azacytidine-treated human mesenchymal stem/progenitor cells derived from umbilical cord, cord blood and bone marrow do not generate cardiomyocytes in vitro at high frequencies.
OBJECTIVE
Mesenchymal stem/progenitor cells (MSCs) are multipotent progenitors that differentiate into such lineages as bone, fat, cartilage and stromal cells that support haemopoiesis. Bone marrow MSCs can also contribute to cardiac repair, although the mechanism for this is unclear. Here, we examine the potential of MSCs from different sources to generate cardiomyocytes in vitro, as a means for predicting their therapeutic potential after myocardial infarction.


METHODS
Mesenchymal stem/progenitor cells were isolated from the perivascular tissue and Wharton's jelly of the umbilical cord and from cord blood. Their immunophenotype and differentiation potential to generate osteoblasts, chondrocytes, adipocytes and cardiomyoxcytes in vitro was compared with those of bone marrow MSCs.


RESULTS
Mesenchymal stem/progenitor cells isolated from umbilical cord and cord blood were phenotypically similar to bone marrow MSCs, the exception being in the expression of CD106, which was absent on umbilical cord MSCs, and CD146 that was highly expressed in cord blood MSCs. They have variable abilities to give rise to osteoblasts, chondrocytes and adipocytes, with bone marrow MSCs being the most robust. While a small proportion (approximately 0.07%) of bone marrow MSCs could generate cardiomyocyte-like cells in vitro, those from umbilical cord and cord blood did not express cardiac markers either spontaneously or after treatment with 5-azacytidine.


CONCLUSIONS
Although MSCs may be useful for such clinical applications as bone or cartilage repair, the results presented here indicate that such cells do not generate cardiomyocytes frequently enough for cardiac repair. Their efficacy in heart repair is likely to be due to paracrine mechanisms.
Martin-Rendon
E
E
Stem Cell Research Laboratory, NHS-Blood and Transplant, John Radcliffe Hospital, Headington, Oxford, UK. enca.rendon@ndcls.ox.ac.uk
Sweeney
D
D
Lu
F
F
Girdlestone
J
J
Navarrete
C
C
Watt
S M
SM
D017667:Adipocytes / Q000166:cytology; D000328:Adult; D000943:Antigens, Differentiation / Q000032:analysis / Q000235:genetics; D001374:Azacitidine / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology; D005240:Feasibility Studies; D005312:Fetal Blood / Q000166:cytology*; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D009124:Muscle Proteins / Q000032:analysis / Q000235:genetics; D032383:Myocytes, Cardiac / Q000166:cytology*; D009928:Organ Specificity; D010006:Osteoblasts / Q000166:cytology; D014470:Umbilical Cord / Q000166:cytology*
D000943:Antigens, Differentiation; D009124:Muscle Proteins; D001374:Azacitidine