Human Cardiac Progenitor Cell Grafts as Unrestricted Source of Supernumerary Cardiac Cells in Healthy Murine Hearts

Abstract

Human heart harbors a population of resident progenitor cells that can be isolated by stem cell antigen-1 antibody and expanded in culture. These cells can differentiate into cardiomyocytes in vitro and contribute to cardiac regeneration in vivo. However, when directly injected as single cell suspension, less than 1%-5% survive and differentiate. Among the major causes of this failure are the distressing protocols used to culture in vitro and implant progenitor cells into damaged hearts. Human cardiac progenitors obtained from the auricles of patients were cultured as scaffoldless engineered tissues fabricated using temperature-responsive surfaces. In the engineered tissue, progenitor cells established proper three-dimensional intercellular relationships and were embedded in self-produced extracellular matrix preserving their phenotype and multipotency in the absence of significant apoptosis. After engineered tissues were leant on visceral pericardium, a number of cells migrated into the murine myocardium and in the vascular walls, where they integrated in the respective textures. The study demonstrates the suitability of such an approach to deliver stem cells to the myocardium. Interestingly, the successful delivery of cells in murine healthy hearts suggests that myocardium displays a continued cell cupidity that is strictly regulated by the limited release of progenitor cells by the adopted source. When an unregulated cell source is added to the system, cells are delivered to the myocardium. The exploitation of this novel concept may pave the way to the setup of new protocols in cardiac cell therapy.

Hippo Pathway Effectors Control Cardiac Progenitor Cell Fate by Acting as Dynamic Sensors of Substrate Mechanics and Nanostructure

“…47,48 Human Sca-1 þ cardiac progenitor cells (hCMPCs or Sca-1 þ hCMPCs) were obtained from human biopsies as previously described 36 and their characterization and differentiation reported. 26 Briefly, human adult auricles were minced and treated with collagenase. By using magnetic cell sorting (MACS, Miltenyi Biotec), hCMPCs were separated with Sca-1 coupled beads.…”

Mesenchymal stem cell adhesion but not plasticity is affected by high substrate stiffness

“…As a result, the impact of microenvironment composition would be more striking on a particular subset, while the other cells could still retain their multipotency and differentiate upon specific stimulation. Therefore, independently of microenvironment changes, stem cell homeostasis preserves a reservoir of undifferentiated progenitors, and the composition of stem cell compartment is tightly regulated [40].…”

Injured cardiomyocytes promote dental pulp mesenchymal stem cell homing

“…Observation that mesenchymal stem cells (MSCs) of both homo-and hetero-topic origins can differentiate in-vitro towards cardiac lineage [6,[9][10][11] provoked increasing interest and perspective about the possibility to restore damaged myocardium with MSCs. Since cells "implanted in" or "delivered to" the target site may frequently vanish within few days, some Authors support the hypothesis that MSCs promote positive actions in terms of cardiac functionality due to production of trophic factors, induction of vasculogenesis, and differentiation into CM [5,6].…”