The Use of Scaffold-free Cell Sheet Technique to Refine Mesenchymal Stromal Cell-based Therapy for Heart Failure

Transplantation of bone marrow-derived mesenchymal stromal cells (MSCs) is an emerging treatment for heart failure based on their secretion-mediated “paracrine effects”. Feasibility of the scaffoldless cell sheet technique to enhance the outcome of cell transplantation has been reported using other...

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Bibliographic Details
Published in:Molecular therapy 2013-04, Vol.21 (4), p.860-867
Main Authors: Narita, Takuya, Shintani, Yasunori, Ikebe, Chiho, Kaneko, Masahiro, Campbell, Niall G, Coppen, Steven R, Uppal, Rakesh, Sawa, Yoshiki, Yashiro, Kenta, Suzuki, Ken
Format: Article
Language:English
Subjects:
Animals
Bone marrow
Cardiac function
Cell- and Tissue-Based Therapy - methods
Cells
Cells, Cultured
Coronary vessels
Dentistry
Ejection fraction
Female
Heart failure
Heart Failure - therapy
Intubation
Male
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - physiology
Original
Polymers
Rats
Retention
Veins & arteries
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Summary:Transplantation of bone marrow-derived mesenchymal stromal cells (MSCs) is an emerging treatment for heart failure based on their secretion-mediated “paracrine effects”. Feasibility of the scaffoldless cell sheet technique to enhance the outcome of cell transplantation has been reported using other cell types, though the mechanism underpinning the enhancement remains uncertain. We here investigated the role of this innovative technique to amplify the effects of MSC transplantation with a focus on the underlying factors. After coronary artery ligation in rats, syngeneic MSCs were grafted by either epicardial placement of MSC sheets generated using temperature-responsive dishes or intramyocardial (IM) injection. Markedly increased initial retention boosted the presence of donor MSCs persistently after MSC sheet placement although the donor survival was not improved. Most of the MSCs grafted by the cell sheet technique remained resided on the epicardial surface, but the epicardium quickly regressed and new vessels sprouted into the sheets, assuring the permeation of paracrine mediators from MSCs into the host myocardium. In fact, there was augmented upregulation of various paracrine effect-related genes and signaling pathways in the early phase after MSC sheet therapy. Correspondingly, more extensive paracrine effects and resultant cardiac function recovery were achieved by MSC sheet therapy. Further development of this approach towards clinical application is encouraged.
ISSN:1525-0016
1525-0024
DOI:10.1038/mt.2013.9