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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

Identification of transplanted hMSC in infracted myocardium.6 weeks after MI: A–C. Representative immunofluorescent micrographs of hearts transplanted with hMSC. A transplanted hMSC could be identified in infarcted myocardium B. A number of hMSC (Arrows, human nuclei in green) were co-localized with CD31 positive cells (red). C. Occasionally hMSC (Arrow, human nuclei in green) co-localized with cardiac troponin positive cell (red). (Confocal image, original magnification 630×) D. Quantitative real-time PCR analysis for human GAPDH expression level at different infarction sections: MI-BM and MI-CB105+ hearts show significantly higher localisation of human cells in the middle and apex section.
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pone-0015652-g007: Identification of transplanted hMSC in infracted myocardium.6 weeks after MI: A–C. Representative immunofluorescent micrographs of hearts transplanted with hMSC. A transplanted hMSC could be identified in infarcted myocardium B. A number of hMSC (Arrows, human nuclei in green) were co-localized with CD31 positive cells (red). C. Occasionally hMSC (Arrow, human nuclei in green) co-localized with cardiac troponin positive cell (red). (Confocal image, original magnification 630×) D. Quantitative real-time PCR analysis for human GAPDH expression level at different infarction sections: MI-BM and MI-CB105+ hearts show significantly higher localisation of human cells in the middle and apex section.

Mentions: We evaluated human GAPDH expression at 3 different parts from the infarction area and identified implanted cells in the mouse tissue 6 weeks after myocardial infarction following hMSC application with selective binding human nuclei antibody (HNA) (Figure 7A). Double immunofluorescence staining with HNA and CD31 antibody revealed that at least some of the hMSC appeared to display endothelial cell-like phenotype (Figure 7B). Six weeks after cell transplantation, we observed a very low number of hMSC colocalized with cardiac Troponin T (cTnT) (Figure 7C). The frequency of cTnT-HNA double-positive cells from the engrafted stem cells was extremely low. There was no significant difference between different hMSC groups. It was not clear whether the transplanted cells had fused or differentiated into cardiomyocytes. Furthermore, higher human GAPDH expression was detected in the lower and the middle section of the infarcted hearts transplanted with BM-hMSC and CD105-purified CB derived hMSC in comparison to MI-AT and MI-CB (Figure 7D). There were no significant differences in the upper heart section.


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)

Identification of transplanted hMSC in infracted myocardium.6 weeks after MI: A–C. Representative immunofluorescent micrographs of hearts transplanted with hMSC. A transplanted hMSC could be identified in infarcted myocardium B. A number of hMSC (Arrows, human nuclei in green) were co-localized with CD31 positive cells (red). C. Occasionally hMSC (Arrow, human nuclei in green) co-localized with cardiac troponin positive cell (red). (Confocal image, original magnification 630×) D. Quantitative real-time PCR analysis for human GAPDH expression level at different infarction sections: MI-BM and MI-CB105+ hearts show significantly higher localisation of human cells in the middle and apex section.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0015652-g007: Identification of transplanted hMSC in infracted myocardium.6 weeks after MI: A–C. Representative immunofluorescent micrographs of hearts transplanted with hMSC. A transplanted hMSC could be identified in infarcted myocardium B. A number of hMSC (Arrows, human nuclei in green) were co-localized with CD31 positive cells (red). C. Occasionally hMSC (Arrow, human nuclei in green) co-localized with cardiac troponin positive cell (red). (Confocal image, original magnification 630×) D. Quantitative real-time PCR analysis for human GAPDH expression level at different infarction sections: MI-BM and MI-CB105+ hearts show significantly higher localisation of human cells in the middle and apex section.
Mentions: We evaluated human GAPDH expression at 3 different parts from the infarction area and identified implanted cells in the mouse tissue 6 weeks after myocardial infarction following hMSC application with selective binding human nuclei antibody (HNA) (Figure 7A). Double immunofluorescence staining with HNA and CD31 antibody revealed that at least some of the hMSC appeared to display endothelial cell-like phenotype (Figure 7B). Six weeks after cell transplantation, we observed a very low number of hMSC colocalized with cardiac Troponin T (cTnT) (Figure 7C). The frequency of cTnT-HNA double-positive cells from the engrafted stem cells was extremely low. There was no significant difference between different hMSC groups. It was not clear whether the transplanted cells had fused or differentiated into cardiomyocytes. Furthermore, higher human GAPDH expression was detected in the lower and the middle section of the infarcted hearts transplanted with BM-hMSC and CD105-purified CB derived hMSC in comparison to MI-AT and MI-CB (Figure 7D). There were no significant differences in the upper heart section.

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