Encapsulated glucagon-like peptide-1-producing mesenchymal stem cells have a beneficial effect on failing pig hearts

Autor: Nadim Malik, Moustapha Kassem, Christine Wallrapp, Elizabeth J. Wright, Cathy M. Holt, Andrew L. Lewis, Kelly A Farrell
Rok vydání: 2012
Předmět:
endocrine system
Stromal cell
Cardiotonic Agents
Angiogenesis
Alginates
Cell Survival
medicine.medical_treatment
Recombinant Fusion Proteins
Sus scrofa
Myocardial Infarction
Apoptosis
Pharmacology
Mesenchymal Stem Cell Transplantation
Ventricular Function
Left
Cell therapy
Paracrine signalling
Drug Delivery Systems
Glucuronic Acid
Glucagon-Like Peptide 1
Tissue Engineering and Regenerative Medicine
In Situ Nick-End Labeling
Medicine
Myocyte
Animals
Humans
Myofibroblasts
Heart Failure
Inflammation
Anatomy
Cross-Sectional
Neovascularization
Pathologic
business.industry
Hexuronic Acids
digestive
oral
and skin physiology
Mesenchymal stem cell
Mesenchymal Stem Cells
Cell Biology
General Medicine
Stem-cell therapy
Disease Models
Animal
Echocardiography
Immunology
Stem cell
business
hormones
hormone substitutes
and hormone antagonists
Developmental Biology
Zdroj: Wright, E J, Farrell, K A, Malik, N, Kassem, M, Lewis, A L, Wallrapp, C & Holt, C M 2012, ' Encapsulated glucagon-like peptide-1-producing mesenchymal stem cells have a beneficial effect on failing pig hearts ', Stem Cells Translational Medicine, vol. 1, no. 10, pp. 759-69 . https://doi.org/10.5966/sctm.2012-0064
ISSN: 2157-6564
DOI: 10.5966/sctm.2012-0064
Popis: Stem cell therapy is an exciting and emerging treatment option to promote post-myocardial infarction (post-MI) healing; however, cell retention and efficacy in the heart remain problematic. Glucagon-like peptide-1 (GLP-1) is an incretin hormone with cardioprotective properties but a short half-life in vivo. The effects of prolonged GLP-1 delivery from stromal cells post-MI were evaluated in a porcine model. Human mesenchymal stem cells immortalized and engineered to produce a GLP-1 fusion protein were encapsulated in alginate (bead-GLP-1 MSC) and delivered to coronary artery branches. Control groups were cell-free beads and beads containing unmodified MSCs (bead-MSC), n = 4–5 per group. Echocardiography confirmed left ventricular (LV) dysfunction at time of delivery in all groups. Four weeks after intervention, only the bead-GLP-1 MSC group demonstrated LV function improvement toward baseline and showed decreased infarction area compared with controls. Histological analysis showed reduced inflammation and a trend toward reduced apoptosis in the infarct zone. Increased collagen but fewer myofibroblasts were observed in infarcts of the bead-GLP-1 MSC and bead-MSC groups, and significantly more vessels per mm2 were noted in the infarct of the bead-GLP-1 MSC group. No differences were observed in myocyte cross-sectional area between groups. Post-MI delivery of GLP-1 encapsulated genetically modified MSCs provided a prolonged supply of GLP-1 and paracrine stem cell factors, which improved LV function and reduced epicardial infarct size. This was associated with increased angiogenesis and an altered remodeling response. Combined benefits of paracrine stem cell factors and GLP-1 were superior to those of stem cells alone. These results suggest that encapsulated genetically modified MSCs would be beneficial for recovery following MI.
Databáze: OpenAIRE
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