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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 | Source: | 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. | Keywords: | co-culture; differentiation; hematopoietic stem cell; mesenchymal stromal cell; myocardial infarction | Document URI: | http://hdl.handle.net/1942/10298 | ISSN: | 1465-3249 | e-ISSN: | 1477-2566 | DOI: | 10.3109/14653240902988818 | ISI #: | 000272042500012 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2010 |
Appears in Collections: | Research publications |
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