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Cell origin of human mesenchymal stem cells determines a different healing performance in cardiac regeneration.

Gaebel R, Furlani D, Sorg H, Polchow B, Frank J, Bieback K, Wang W, Klopsch C, Ong LL, Li W, Ma N, Steinhoff G - PLoS ONE (2011)

Bottom Line: Six weeks post infarction, cardiac catheterization showed significant preservation of left ventricular functions in BM and CD105(+)-CB treated groups compared to CB and nontreated MI group (MI-C).Furthermore, cardiac remodeling can be significantly attenuated by BM-hMSC compared to MI-C.Under hypoxic conditions in vitro, remarkably increased extracellular acidification and apoptosis has been detected from CB-hMSC compared to BM and CD105 purified CB-derived hMSC.

View Article: PubMed Central - PubMed

Affiliation: Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, University of Rostock, Rostock, Germany.

ABSTRACT
The possible different therapeutic efficacy of human mesenchymal stem cells (hMSC) derived from umbilical cord blood (CB), adipose tissue (AT) or bone marrow (BM) for the treatment of myocardial infarction (MI) remains unexplored. This study was to assess the regenerative potential of hMSC from different origins and to evaluate the role of CD105 in cardiac regeneration. Male SCID mice underwent LAD-ligation and received the respective cell type (400.000/per animal) intramyocardially. Six weeks post infarction, cardiac catheterization showed significant preservation of left ventricular functions in BM and CD105(+)-CB treated groups compared to CB and nontreated MI group (MI-C). Cell survival analyzed by quantitative real time PCR for human GAPDH and capillary density measured by immunostaining showed consistent results. Furthermore, cardiac remodeling can be significantly attenuated by BM-hMSC compared to MI-C. Under hypoxic conditions in vitro, remarkably increased extracellular acidification and apoptosis has been detected from CB-hMSC compared to BM and CD105 purified CB-derived hMSC. Our findings suggests that hMSC originating from different sources showed a different healing performance in cardiac regeneration and CD105(+) hMSC exhibited a favorable survival pattern in infarcted hearts, which translates into a more robust preservation of cardiac function.

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Related in: MedlinePlus

Late cardiomyocytes apoptosis.A. Representative immunostaining for TUNEL (green) and cardiac troponin (red) at the BZ 6 weeks after MI. B. Cardiomyocytes apoptosis was significantly reduced in the BZ in MI-BM and MI-CB105+ compared to MI-C.
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pone-0015652-g006: Late cardiomyocytes apoptosis.A. Representative immunostaining for TUNEL (green) and cardiac troponin (red) at the BZ 6 weeks after MI. B. Cardiomyocytes apoptosis was significantly reduced in the BZ in MI-BM and MI-CB105+ compared to MI-C.

Mentions: Postinfarct cardiac remodeling serves as an important compensatory mechanism of congestive heart failure, characterized by progressive ventricular chamber dilatation, hypertrophy, fibrosis and prolonged cardiomyocyte apoptosis. Fibrosis resulted in extensive collagen deposition (Sirius red) and increased distance between myocytes (Fast green) 6 weeks after infarction. Figure 5A shows representative staining images from the BZ indicating a higher portion of collagen deposition in the MI-CB and the MI-C group. Hearts implanted with CD105-purified CB-hMSC showed a significant decrease of collagen deposition compared to MI-CB and the MI-C group, respectively in RA and in the BZ (Figure 5B). Figure 6A represents apoptotic nuclei of cardiomyocytes 6 weeks after myocardial infarction. A significantly reduced percentage of apoptotic cardiomyocytes could be found in the BZ of hearts implanted with CD105-purified CB-hMSC and BM-hMSC, respectively, compared to the MI-C group (Figure 6B).


Cell origin of human mesenchymal stem cells determines a different healing performance in cardiac regeneration.

Gaebel R, Furlani D, Sorg H, Polchow B, Frank J, Bieback K, Wang W, Klopsch C, Ong LL, Li W, Ma N, Steinhoff G - PLoS ONE (2011)

Late cardiomyocytes apoptosis.A. Representative immunostaining for TUNEL (green) and cardiac troponin (red) at the BZ 6 weeks after MI. B. Cardiomyocytes apoptosis was significantly reduced in the BZ in MI-BM and MI-CB105+ compared to MI-C.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3037376&req=5

pone-0015652-g006: Late cardiomyocytes apoptosis.A. Representative immunostaining for TUNEL (green) and cardiac troponin (red) at the BZ 6 weeks after MI. B. Cardiomyocytes apoptosis was significantly reduced in the BZ in MI-BM and MI-CB105+ compared to MI-C.
Mentions: Postinfarct cardiac remodeling serves as an important compensatory mechanism of congestive heart failure, characterized by progressive ventricular chamber dilatation, hypertrophy, fibrosis and prolonged cardiomyocyte apoptosis. Fibrosis resulted in extensive collagen deposition (Sirius red) and increased distance between myocytes (Fast green) 6 weeks after infarction. Figure 5A shows representative staining images from the BZ indicating a higher portion of collagen deposition in the MI-CB and the MI-C group. Hearts implanted with CD105-purified CB-hMSC showed a significant decrease of collagen deposition compared to MI-CB and the MI-C group, respectively in RA and in the BZ (Figure 5B). Figure 6A represents apoptotic nuclei of cardiomyocytes 6 weeks after myocardial infarction. A significantly reduced percentage of apoptotic cardiomyocytes could be found in the BZ of hearts implanted with CD105-purified CB-hMSC and BM-hMSC, respectively, compared to the MI-C group (Figure 6B).

Bottom Line: Six weeks post infarction, cardiac catheterization showed significant preservation of left ventricular functions in BM and CD105(+)-CB treated groups compared to CB and nontreated MI group (MI-C).Furthermore, cardiac remodeling can be significantly attenuated by BM-hMSC compared to MI-C.Under hypoxic conditions in vitro, remarkably increased extracellular acidification and apoptosis has been detected from CB-hMSC compared to BM and CD105 purified CB-derived hMSC.

View Article: PubMed Central - PubMed

Affiliation: Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Department of Cardiac Surgery, University of Rostock, Rostock, Germany.

ABSTRACT
The possible different therapeutic efficacy of human mesenchymal stem cells (hMSC) derived from umbilical cord blood (CB), adipose tissue (AT) or bone marrow (BM) for the treatment of myocardial infarction (MI) remains unexplored. This study was to assess the regenerative potential of hMSC from different origins and to evaluate the role of CD105 in cardiac regeneration. Male SCID mice underwent LAD-ligation and received the respective cell type (400.000/per animal) intramyocardially. Six weeks post infarction, cardiac catheterization showed significant preservation of left ventricular functions in BM and CD105(+)-CB treated groups compared to CB and nontreated MI group (MI-C). Cell survival analyzed by quantitative real time PCR for human GAPDH and capillary density measured by immunostaining showed consistent results. Furthermore, cardiac remodeling can be significantly attenuated by BM-hMSC compared to MI-C. Under hypoxic conditions in vitro, remarkably increased extracellular acidification and apoptosis has been detected from CB-hMSC compared to BM and CD105 purified CB-derived hMSC. Our findings suggests that hMSC originating from different sources showed a different healing performance in cardiac regeneration and CD105(+) hMSC exhibited a favorable survival pattern in infarcted hearts, which translates into a more robust preservation of cardiac function.

Show MeSH
Related in: MedlinePlus