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In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
Published on: August 9, 2017
Angiogenic and reparative potency of a human cardiac CD90- mesenchymal subpopulation in heart ischemic model
Elisa Gambini1, Erica Rurali2, Veronica Barbagallo2
1Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS; Via Carlo Parea 4, 20138 Milan, Italy; Oloker Therapeutics; Piazza Massari 19, 70122 Bari, Italy.
Insights
A novel cell therapy using CD90-negative human cardiac mesenchymal progenitor cells (hCmPC90-) shows promise for treating heart disease. These cells demonstrated superior cardiac repair and functional recovery in preclinical models.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Cell Biology
Background:
- Cardiovascular diseases (CVD) represent a significant global health burden despite therapeutic advancements.
- Current cell-based therapies for CVD show modest efficacy, necessitating novel strategies.
Purpose of the Study:
- To characterize a novel subpopulation of CD90-negative human cardiac mesenchymal progenitor cells (hCmPC90-).
- To evaluate the potential of hCmPC90- cells in promoting cardiac tissue repair and functional recovery.
Main Methods:
- Comprehensive phenotypic analysis of hCmPC90- using flow cytometry and RNA sequencing.
- In vitro functional assays assessing angiogenic potency, anti-inflammatory, and cardio-protective capacities.
- In vivo evaluation in a mouse model of acute myocardial infarction (AMI) to assess cardiac function and remodeling.
Main Results:
- hCmPC90- cells exhibit distinct surface markers and transcriptional profiles compared to other mesenchymal cells.
- In vitro, hCmPC90- demonstrated superior endothelial differentiation, anti-inflammatory, cardio-protective, and angiocrine activities.
- In vivo, hCmPC90- improved left ventricular function, reduced infarct size, and enhanced vascularization post-AMI compared to other cell types.
Conclusions:
- hCmPC90- cells possess superior biological potency for cardiac repair.
- These findings support the clinical development of hCmPC90- as an advanced therapy for ischemic heart disease.
Background:
Despite recent significant therapeutic progress, cardiovascular diseases (CVD) remain an unmet clinical, economic, and social burden worldwide. Cell-based therapies have been proposed as therapeutic strategies, however, the overall efficacy was modest.
Objective:
We aimed to fully characterize a novel subpopulation of CD90- mesenchymal cells derived from human heart tissue (hCmPC90-) and evaluate its ability to induce cardiac tissue repair and functional recovery.
Methods:
We performed a comprehensive phenotypic characterization of the hCmPC90- by flow cytometry and RNA sequencing. A direct comparison of hCmPC90- with previously clinically tested bone marrow- and cardiac-derived cell types, has been conducted both in vitro by means of various assays of angiogenic potency, and in vivo, by testing the ability to ameliorate left ventricular function in a mouse model of acute myocardial infarction (AMI).
Results:
hCmPC90- showed distinct surface markers and transcriptional phenotype compared with unselected mesenchymal heart cells (hCmPCs) and the positive CD90 counterpart (hCmPC90+). When human hCmPC90-, hCmPC90+, hCmPC, cardiosphere-derived cells (CDCs), and bone marrow-derived CD34+ cells were functionally tested in vitro, hCmPC90- revealed a superior endothelial differentiation ability, higher anti-inflammatory, cardio-protective capacity, and angiocrine activity. Moreover, hCmPC90- showed specific immune-privileged features. When intramyocardially delivered into infarcted mouse hearts, hCmPC90- outperformed three weeks after injection other clinical-grade cell types, as for left ventricular (LV) function and adverse LV remodeling recovery, infarct size reduction, and vascular density augmentation.
Conclusion:
hCmPC90- shows a superior biological potency which deserves clinical exploitation as an advanced therapy medicinal product in the context of refractory ischemic heart disease.
