Cell Origin of Human Mesenchymal Stem Cells Determines a Different Healing Performance in Cardiac Regeneration

Abstract

The possible different therapeutic efficacy of human mesenchymal stem cells (hMSC) derived from umbilical cord blood (CB), adipose tissue (AT) or bone marrow (BM) for the treatment of myocardial infarction (MI) remains unexplored. This study was to assess the regenerative potential of hMSC from different origins and to evaluate the role of CD105 in cardiac regeneration. Male SCID mice underwent LAD-ligation and received the respective cell type (400.000/per animal) intramyocardially. Six weeks post infarction, cardiac catheterization showed significant preservation of left ventricular functions in BM and CD105+-CB treated groups compared to CB and nontreated MI group (MI-C). Cell survival analyzed by quantitative real time PCR for human GAPDH and capillary density measured by immunostaining showed consistent results. Furthermore, cardiac remodeling can be significantly attenuated by BM-hMSC compared to MI-C. Under hypoxic conditions in vitro, remarkably increased extracellular acidification and apoptosis has been detected from CB-hMSC compared to BM and CD105 purified CB-derived hMSC. Our findings suggests that hMSC originating from different sources showed a different healing performance in cardiac regeneration and CD105+ hMSC exhibited a favorable survival pattern in infarcted hearts, which translates into a more robust preservation of cardiac function.

Defining Optimized Properties of Modified mRNA to Enhance Virus- and DNA- Independent Protein Expression in Adult Stem Cells and Fibroblasts

“…hMSCs were obtained from bone marrow aspirates of patients during coronary artery bypass grafting as previously described [33]. All donors gave their written consent to use their bone marrow for research proposes according to the Declaration of Helsinki.…”

How do Mesenchymal Stem Cells Repair?

“…Studies show that MSC are capable of inhibiting apoptosis in kidney, liver and brain injuries (30,(131)(132)(133). Recent evidence shows that this is done through increasing prosurvival factors as Akt expression in injured cells (55), BDNF and growth factors as IGF, VEGF and HGF expression which inhibit apoptosis and stimulate cell proliferation (134,135).…”

The Impact of Cell Source, Culture Methodology, Culture Location, and Individual Donors on Gene Expression Profiles of Bone Marrow-Derived and Adipose-Derived Stromal Cells

“…Based on their immunosuppressive function, they were considered ideal donor cells to repair heart tissue affected by myocardial infarction or ischemic brain injury [4][5][6][7][8]. The differences in differentiation abilities that were observed by different laboratories were initially assigned to the use of different sources and culture conditions of MSCs [9]. However, several reports described functional as well as phenotypic heterogeneity of MSCs, which is also reflected by their diverse nomenclature: mesenchymal stem cells, bone MSCs, or multipotent stromal cells [10][11][12][13][14][15][16][17][18][19].…”