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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/10298

Title: Human bone marrow stem cells co-cultured with neonatal rat cardiomyocytes display limited cardiomyogenic plasticity
Authors: KONINCKX, Remco
Hensen, Karen
Daniels, Annick
MOREELS, Marjan
LAMBRICHTS, Ivo
Jongen, Hanne
Clijsters, Christel
Mees, Urbain
STEELS, Paul
HENDRIKX, Marc
RUMMERS, Jean-Luc
Issue Date: 2009
Publisher: TAYLOR & FRANCIS AS
Citation: CYTOTHERAPY, 11(6). p. 778-792
Abstract: Background aims This study investigated whether neonatal rat cardiomyocytes (NRCM), when co-cultured, can induce transdifferentiation of either human mesenchymal stromal cells (MSC) or hematopoietic stem cells (HSC) into cardiomyocytes. Stem cells were obtained from patients with ischemic heart disease. Methods Ex vivo-expanded MSC or freshly isolated HSC were used to set-up a co-culture system between NRCM and MSC or HSC. 5-azacytidin (5-aza) or dimethylsulfoxide (DMSO) was used as differentiation-inducing factor. Co-cultured stem cells were separated from NRCM by flow sorting, and cardiac gene expression was analyzed by reverse transcriptase-polymerase chain reaction. Cellular morphology was analyzed by immunofluorescence and transmission electron microscopy (TEM). Results Co-culturing MSC induced expression of troponin T and GATA-4. However, no expression of a-actinin, myosin heavy chain or troponin I was detected. In the case of HSC, only expression of troponin T could be induced. Immunofluorescence and TEM confirmed the absence of sarcomeric organization in co-cultured MSC and HSC. Adding 5-aza or DMSO to the co-cultures did not influence differentiation. Conclusions This in vitro co-culture study obtained no convincing evidence of transdifferentiation of either MSC or HSC into functional cardiomyocytes. Nevertheless, induction of troponin T was observed in MSC and HSC, and GATA-4 in MSC. However, no morphologic changes could be detected by immunofluorescence or by TEM. These data could explain why only limited functional improvement was reported in clinical stem cell trials.
Notes: [Mees, Urbain; Hendrikx, Marc] Virga Jesseziekenhuis, Dept Cardiothorac Surg, B-3500 Hasselt, Belgium. [Koninckx, Remco; Hensen, Karen; Daniels, Annick; Jongen, Hanne; Clijsters, Christel; Rummens, Jean-Luc] Virga Jesseziekenhuis, Lab Expt Hematol, B-3500 Hasselt, Belgium. [Koninckx, Remco; Steels, Paul; Hendrikx, Marc; Rummens, Jean-Luc] Hasselt Univ, Physiol Lab, Fac Med, Biomed Res Inst, Diepenbeek, Belgium. [Koninckx, Remco; Steels, Paul; Hendrikx, Marc; Rummens, Jean-Luc] Hasselt Univ, Biomed Res Inst, Sch Life Sci, Diepenbeek, Belgium. [Koninckx, Remco; Moreels, Marjan; Lambrichts, Ivo; Steels, Paul; Hendrikx, Marc; Rummens, Jean-Luc] Transnat Univ Limburg, Diepenbeek, Belgium. [Moreels, Marjan; Lambrichts, Ivo] Hasselt Univ, Histol Lab, Sch Life Sci, Biomed Res Inst, Diepenbeek, Belgium.
URI: http://hdl.handle.net/1942/10298
DOI: 10.3109/14653240902988818
ISI #: 000272042500012
ISSN: 1465-3249
Category: A1
Type: Journal Contribution
Validation: ecoom, 2010
Appears in Collections: Research publications

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