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Early homing of adult mesenchymal stem cells in normal and infarcted isolated beating hearts.

Penna C, Raimondo S, Ronchi G, Rastaldo R, Mancardi D, Cappello S, Losano G, Geuna S, Pagliaro P - J. Cell. Mol. Med. (2008)

Bottom Line: Moreover, a few hours after injection connexin-43 is well evident between cardiomyocytes and injected cells.This study indicates for the first time that the isolated beating heart is a good model to study early features of MSC homing without external interferences.The results show (i) that MSCs start to change marker expression few hours after injection into a beating heart and (ii) that infarcted myocardium influences transplanted MSC morphology and mobility within the heart.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Biological Sciences, University of Turin, Italy.

ABSTRACT
Little is known on the early homing features of transplanted mesenchymal stem cells (MSCs). We used the isolated rat heart model to study the homing of MSCs injected in the ventricular wall of a beating heart. In this model all types of cells and matrix elements with their interactions are represented, while external interferences by endothelial/neutrophil interaction and neurohormonal factors are excluded. We studied the morphology and marker expression of MSCs implanted in normal hearts and in the border-zone of infarcted myocardium. Early morphological adaptation of MSC homing differs between normal and infarcted hearts over the first 6 hrs after transplantation. In normal hearts, MSCs migrate very early through the interstitial milieu and begin to show morphological changes. Yet, in infarcted hearts MSCs remain in the site of injection forming clusters of round-shaped cells in the border-zone of the infarcted area. Both in normal and infarcted hearts, immuno-histochemistry and confocal imaging showed that, besides the proliferative marker proliferating cell nuclear agent (PCNA), some transplanted cells early express myoblastic maker GATA-4, and some of them show a VWF immunopositivity. Moreover, a few hours after injection connexin-43 is well evident between cardiomyocytes and injected cells. This study indicates for the first time that the isolated beating heart is a good model to study early features of MSC homing without external interferences. The results show (i) that MSCs start to change marker expression few hours after injection into a beating heart and (ii) that infarcted myocardium influences transplanted MSC morphology and mobility within the heart.

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Confocal imaging of direct fluorescence GFP-positive MSCs (green) and nuclear immunostaining with anti-GATA-4 antibody (red) in normal (A) and infarcted (B) hearts. (C, D) Immunostaining with α-actinin antibody (red in C) or troponin T (red in D) in normal hearts 4hrs after injection. Where the red labellingis superimposed to the green, the system displays it yellow. Scale bars: 20 μm.
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fig08: Confocal imaging of direct fluorescence GFP-positive MSCs (green) and nuclear immunostaining with anti-GATA-4 antibody (red) in normal (A) and infarcted (B) hearts. (C, D) Immunostaining with α-actinin antibody (red in C) or troponin T (red in D) in normal hearts 4hrs after injection. Where the red labellingis superimposed to the green, the system displays it yellow. Scale bars: 20 μm.

Mentions: Despite the fact that changes in the morphological phenotype demonstrated by histological examination were observed in the normal hearts only (Fig. 4), confocal imaging after a-connexin-43 (Fig. 7) and a-GATA4 (Fig. 8A and B) immunolabelling showed similar signs of differentiation of transplanted MSCs in both normal and ischaemic heart. In myocardium of both normal (Fig. 7A–C). and infarcted hearts (Fig. 7D and E), connexin-43, a protein that is mainly localized in the intercalated disks (Fig. 7 arrows), was present between resident cardiomyocytes and transplanted MSCs only 2 hrs after transplantation. It is noteworthy that, though the location was different, even in P6 cultured MSCs we detected the presence of a-connexin-43 (Fig. 7F–H) as also reported by Gallo et al.[12] in P3-P10 MSCs.


Early homing of adult mesenchymal stem cells in normal and infarcted isolated beating hearts.

Penna C, Raimondo S, Ronchi G, Rastaldo R, Mancardi D, Cappello S, Losano G, Geuna S, Pagliaro P - J. Cell. Mol. Med. (2008)

Confocal imaging of direct fluorescence GFP-positive MSCs (green) and nuclear immunostaining with anti-GATA-4 antibody (red) in normal (A) and infarcted (B) hearts. (C, D) Immunostaining with α-actinin antibody (red in C) or troponin T (red in D) in normal hearts 4hrs after injection. Where the red labellingis superimposed to the green, the system displays it yellow. Scale bars: 20 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822539&req=5

fig08: Confocal imaging of direct fluorescence GFP-positive MSCs (green) and nuclear immunostaining with anti-GATA-4 antibody (red) in normal (A) and infarcted (B) hearts. (C, D) Immunostaining with α-actinin antibody (red in C) or troponin T (red in D) in normal hearts 4hrs after injection. Where the red labellingis superimposed to the green, the system displays it yellow. Scale bars: 20 μm.
Mentions: Despite the fact that changes in the morphological phenotype demonstrated by histological examination were observed in the normal hearts only (Fig. 4), confocal imaging after a-connexin-43 (Fig. 7) and a-GATA4 (Fig. 8A and B) immunolabelling showed similar signs of differentiation of transplanted MSCs in both normal and ischaemic heart. In myocardium of both normal (Fig. 7A–C). and infarcted hearts (Fig. 7D and E), connexin-43, a protein that is mainly localized in the intercalated disks (Fig. 7 arrows), was present between resident cardiomyocytes and transplanted MSCs only 2 hrs after transplantation. It is noteworthy that, though the location was different, even in P6 cultured MSCs we detected the presence of a-connexin-43 (Fig. 7F–H) as also reported by Gallo et al.[12] in P3-P10 MSCs.

Bottom Line: Moreover, a few hours after injection connexin-43 is well evident between cardiomyocytes and injected cells.This study indicates for the first time that the isolated beating heart is a good model to study early features of MSC homing without external interferences.The results show (i) that MSCs start to change marker expression few hours after injection into a beating heart and (ii) that infarcted myocardium influences transplanted MSC morphology and mobility within the heart.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Biological Sciences, University of Turin, Italy.

ABSTRACT
Little is known on the early homing features of transplanted mesenchymal stem cells (MSCs). We used the isolated rat heart model to study the homing of MSCs injected in the ventricular wall of a beating heart. In this model all types of cells and matrix elements with their interactions are represented, while external interferences by endothelial/neutrophil interaction and neurohormonal factors are excluded. We studied the morphology and marker expression of MSCs implanted in normal hearts and in the border-zone of infarcted myocardium. Early morphological adaptation of MSC homing differs between normal and infarcted hearts over the first 6 hrs after transplantation. In normal hearts, MSCs migrate very early through the interstitial milieu and begin to show morphological changes. Yet, in infarcted hearts MSCs remain in the site of injection forming clusters of round-shaped cells in the border-zone of the infarcted area. Both in normal and infarcted hearts, immuno-histochemistry and confocal imaging showed that, besides the proliferative marker proliferating cell nuclear agent (PCNA), some transplanted cells early express myoblastic maker GATA-4, and some of them show a VWF immunopositivity. Moreover, a few hours after injection connexin-43 is well evident between cardiomyocytes and injected cells. This study indicates for the first time that the isolated beating heart is a good model to study early features of MSC homing without external interferences. The results show (i) that MSCs start to change marker expression few hours after injection into a beating heart and (ii) that infarcted myocardium influences transplanted MSC morphology and mobility within the heart.

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