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Progenitor/stem cell transplantation for repair of myocardial infarction: Hype or hope?

ABSTRACT: Despite significant therapeutic advances, heart failure remains the predominant cause of mortality worldwide. Currently, progenitor/stem cell biology holds great promise for a new era of cell-based therapy for salvaging the failing heart. However, the translational arm of progenitor/stem cell science is in a relatively primitive state. For the time being, the clinical trials have been both encouraging and disappointing. How to improve the engraftment, long-term survival and appropriate differentiation of transplanted progenitor/stem cell within the cardiovascular tissues may be the key issues to facilitate the transition of cardiogenic stem cell research from bench to bedside. In this review article we discuss the state-of-the-art in adult stem cell therapies for cardiovascular diseases and approaches to release cardiac regeneration potentials of progenitor/stem cells.

SUBMITTER: Feng Y

PROVIDER: S-EPMC3402094 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Progenitor/stem cell transplantation for repair of myocardial infarction: Hype or hope?

Feng Yuliang Y Wang Yuhua Y Cao Nan N Yang Huangtian H Wang Yigang Y

Annals of palliative medicine 20120101 1

Despite significant therapeutic advances, heart failure remains the predominant cause of mortality worldwide. Currently, progenitor/stem cell biology holds great promise for a new era of cell-based therapy for salvaging the failing heart. However, the translational arm of progenitor/stem cell science is in a relatively primitive state. For the time being, the clinical trials have been both encouraging and disappointing. How to improve the engraftment, long-term survival and appropriate different ...[more]

PMID: 22833840

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Project description:Background: Bone marrow-derived multipotent progenitor cell (MPC) transplantation leads to short term functional and bioenergetic improvement in a porcine model of postinfarction Left Ventricular (LV) remodeling despite a low engraftment rate. However, the long term outcome after MPC transplantation is unknown. Methods and Results: The objectives of this study were to determine the long term functional outcome after MPC transplantation in a porcine model of postinfarction LV remodeling and to elucidate its mechanisms. Myocardial infarction (MI) was created by ligating the first and second diagonal branches of the Left anterior descending artery after open thoracotomy. Intramyocardial injection of 50 million lacZ labeled MPC was performed in the periscar region (Cell, n=7) with 5 equal injections immediately after MI, while in control animals (CONT, n=7; only 6 were profiled by microarray) saline was injected. Outcome was assessed temporally for 4 months with MRI and P-31 MRS. Engraftment was studied on histology and gene chip (Affymetrix) array analysis was used to study differential expression of genes in the two groups at 4 months. MPC treatment resulted in improvement of ejection fraction as early as 10 days after MI (32.2Â±5.5 vs. 43.4Â±5.1 in CONT and Cell respectively, p <0.05). This improvement was seen each month and persisted up to 4 months (35.7Â±5.0 vs. 51.2Â±4.8 in CONT and Cell respectively, p<0.005). PCr/ATP ratio improved with MPC transplantation (1.88Â±0.11 vs. 2.13Â±0.13 in CONT and Cell respectively, p<0.05). Under increased workload with inotropic stimulation, the bioenergetic differences were even more pronounced. There was no significant difference in scar size (scar/LV area*100) at 10 days post infarction (9.7Â±2.3 vs. 8.3Â±1.5 in CONT and Cell respectively). However, at 4 months there was a significant decrease in scar size in the MPC treated animals (8.6Â±2.4 vs. 4.6Â±1.0 in CONT and Cell respectively, p <0.05). No significant engraftment of MPC was observed on histology at 4 months. Gene chip array analysis identified several genes which were differentially expressed in the two groups. MPC transplantation was associated with a downregulation of mitochondrial oxidative enzymes, increased levels of MEF2a (Myocyte Enhancer Factor 2a) and ZFP91 (Zinc finger protein 91). Conclusion: MPC transplantation results in long term improvement in ventricular function and myocardial energetics that is associated with a decreased scar size and differential expression of genes. 13 swine were randomized after myocardial infarction to receive either 50 million stem cells (n=7) or saline only (n=6). The pigs were followed for a total of 4 months after transplantation with MRI occurring at baseline, 10 days, 1 month and then subsequently each month for 4 months. At the end of the study open-chest NMR spectroscopy was performed and then after sacrifice histology and microarray analysis was done on the tissue samples.

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Progenitor/stem cell transplantation for repair of myocardial infarction: Hype or hope?

Publications

Progenitor/stem cell transplantation for repair of myocardial infarction: Hype or hope?

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