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Transplantation of expanded bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) improves left ventricular function and remodelling after myocardial infarction.

ABSTRACT: Adult bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) exhibit a Sca-1(+)/Lin(-)/CD45(-) phenotype and can differentiate into various cell types, including cardiomyocytes and endothelial cells. We have previously reported that transplantation of a small number (1 × 10(6)) of freshly isolated, non-expanded VSEL-SCs into infarcted mouse hearts resulted in improved left ventricular (LV) function and anatomy. Clinical translation, however, will require large numbers of cells. Because the frequency of VSEL-SCs in the marrow is very low, we examined whether VSEL-SCs can be expanded in culture without loss of therapeutic efficacy. Mice underwent a 30 min. coronary occlusion followed by reperfusion and, 48 hrs later, received an intramyocardial injection of vehicle (group I, n = 11), 1 × 10(5) enhanced green fluorescent protein (EGFP)-labelled expanded untreated VSEL-SCs (group II, n = 7), or 1 × 10(5) EGFP-labelled expanded VSEL-SCs pre-incubated in a cardiogenic medium (group III, n = 8). At 35 days after myocardial infarction (MI), mice treated with pre-incubated VSEL-SCs exhibited better global and regional LV systolic function and less LV hypertrophy compared with vehicle-treated controls. In contrast, transplantation of expanded but untreated VSEL-SCs did not produce appreciable reparative benefits. Scattered EGFP(+) cells expressing α-sarcomeric actin, platelet endothelial cell adhesion molecule (PECAM)-1, or von Willebrand factor were present in VSEL-SC-treated mice, but their numbers were very small. No tumour formation was observed. We conclude that VSEL-SCs expanded in culture retain the ability to alleviate LV dysfunction and remodelling after a reperfused MI provided that they are exposed to a combination of cardiomyogenic growth factors and cytokines prior to transplantation. Counter intuitively, the mechanism whereby such pre-incubation confers therapeutic efficacy does not involve differentiation into new cardiac cells. These results support the potential therapeutic utility of VSEL-SCs for cardiac repair.

SUBMITTER: Zuba-Surma EK

PROVIDER: S-EPMC3064954 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Transplantation of expanded bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) improves left ventricular function and remodelling after myocardial infarction.

Zuba-Surma Ewa K EK Guo Yiru Y Taher Hisham H Sanganalmath Santosh K SK Hunt Greg G Vincent Robert J RJ Kucia Magda M Abdel-Latif Ahmed A Tang Xian-Liang XL Ratajczak Mariusz Z MZ Dawn Buddhadeb B Bolli Roberto R

Journal of cellular and molecular medicine 20100712 6

Adult bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) exhibit a Sca-1(+)/Lin(-)/CD45(-) phenotype and can differentiate into various cell types, including cardiomyocytes and endothelial cells. We have previously reported that transplantation of a small number (1 × 10(6)) of freshly isolated, non-expanded VSEL-SCs into infarcted mouse hearts resulted in improved left ventricular (LV) function and anatomy. Clinical translation, however, will require large numbers of cells. Beca ...[more]

PMID: 20629987

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Project description:AimsLeft ventricular (LV) remodelling after acute myocardial infarction (AMI) is associated with heart failure and increased mortality. There was no consensus on the definition of LV remodelling, and the prognostic value of LV remodelling with different definitions has not been compared. We aimed to find the optimal definition and develop a prediction nomogram as well as online calculator that can identify patients at risk of LV remodelling.Methods and resultsThis prospective, observational study included 829 AMI patients undergoing percutaneous coronary intervention from January 2015 to January 2020. Echocardiography was performed within the 48 h of admission and at 6 months after infarction to evaluate LV remodelling, defined as a 20% increase in LV end-diastolic volume (LVEDV), a 15% increase in LV end-systolic volume (LVESV), or LV ejection fraction (LVEF) < 50% at 6 months. The impact of LV remodelling on long-term outcomes was analysed. Lasso regression was performed to screen potential predictors, and multivariable logistic regression analysis was conducted to establish the prediction nomogram. The area under the curve, calibration curve and decision curve analyses were used to determine the discrimination, calibration and clinical usefulness of the remodelling nomogram. The incidences of LV remodelling defined by LVEDV, LVESV and LVEF were 24.85% (n = 206), 28.71% (n = 238) and 14.60% (n = 121), respectively. Multivariable Cox regression models demonstrated that different definitions of LV remodelling were independently associated with the composite endpoint. However, only remodelling defined by LVEF was significantly connected with long-term mortality (hazard ratio = 2.78, 95% confidence interval 1.41-5.48, P = 0.003). Seven variables were selected to construct the remodelling nomogram, including diastolic blood pressure, heart rate, AMI type, stent length, N-terminal pro brain natriuretic peptide, troponin I, and glucose. The prediction model had an area under the receiver operating characteristics curve of 0.766. The calibration curve and decision curve analysis indicated consistency and better net benefit in the prediction model.ConclusionsLV remodelling defined by LVEDV, LVESV and LVEF were independent predictors for long-term mortality or heart failure hospitalization in AMI patients after percutaneous coronary intervention. However, only remodelling defined by LVEF was suitable for predicting all-cause death. In addition, the nomogram can provide an accurate and effective tool for the prediction of postinfarct remodelling.

Dataset Information

Transplantation of expanded bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) improves left ventricular function and remodelling after myocardial infarction.

Publications

Transplantation of expanded bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) improves left ventricular function and remodelling after myocardial infarction.

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