title: Early homing of adult mesenchymal stem cells in normal and infarcted isolated beating hearts.
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.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Penna
authors.forename: Stefania
authors.initials: S
authors.lastname: Raimondo
authors.forename: Giulia
authors.initials: G
authors.lastname: Ronchi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Rastaldo
authors.forename: Daniele
authors.initials: D
authors.lastname: Mancardi
authors.forename: Sandra
authors.initials: S
authors.lastname: Cappello
authors.forename: Gianni
authors.initials: G
authors.lastname: Losano
authors.forename: Stefano
authors.initials: S
authors.lastname: Geuna
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pagliaro
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D015415:Biomarkers; D049452:Green Fluorescent Proteins