title: Can the outcomes of mesenchymal stem cell-based therapy for myocardial infarction be improved? Providing weapons and armour to cells.
abstract: Use of mesenchymal stem cell (MSC) transplantation after myocardial infarction (MI) has been found to have infarct-limiting effects in numerous experimental and clinical studies. However, recent meta-analyses of randomized clinical trials on MSC-based MI therapy have highlighted the need for improving its efficacy. There are two principal approaches for increasing therapeutic effect of MSCs: (i) preventing massive MSC death in ischaemic tissue and (ii) increasing production of cardioreparative growth factors and cytokines with transplanted MSCs. In this review, we aim to integrate our current understanding of genetic approaches that are used for modification of MSCs to enable their improved survival, engraftment, integration, proliferation and differentiation in the ischaemic heart. Genetic modification of MSCs resulting in increased secretion of paracrine factors has also been discussed. In addition, data on MSC preconditioning with physical, chemical and pharmacological factors prior to transplantation are summarized. MSC seeding on three-dimensional polymeric scaffolds facilitates formation of both intercellular connections and contacts between cells and the extracellular matrix, thereby enhancing cell viability and function. Use of genetic and non-genetic approaches to modify MSC function holds great promise for regenerative therapy of myocardial ischaemic injury.
authors.affiliation: Institute of Experimental Medicine, Federal Almazov North-West Medical Research Centre, St Petersburg, Russia.|Department of Pathophysiology, First Pavlov State Medical University of Saint Petersburg, St Petersburg, Russia.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Karpov
authors.affiliation: Institute of Experimental Medicine, Federal Almazov North-West Medical Research Centre, St Petersburg, Russia.
authors.forename: Daria V
authors.initials: DV
authors.lastname: Udalova
authors.affiliation: Institute of Experimental Medicine, Federal Almazov North-West Medical Research Centre, St Petersburg, Russia.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Pliss
authors.affiliation: Institute of Experimental Medicine, Federal Almazov North-West Medical Research Centre, St Petersburg, Russia.|ITMO University, St Petersburg, Russia.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Galagudza
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009203:Myocardial Infarction / Q000628:therapy*; D012038:Regeneration / Q000502:physiology*
keywords: conditioning; genetic modification; heart failure; mesenchymal stem cells; microencapsulation; myocardial infarction