Myocardial Repair Achieved by the Intramyocardial Implantation of Adult Cardiomyocytes in Combination with Bone Marrow Cells

Abstract

Various cytokines produced by bone marrow cells can protect adult cardiomyocytes against apoptosis. Thus, we investigated the feasibility of implanting adult cardiomyocytes in combination with bone marrow cells for myocardial repair. Ventricular cardiomyocytes were isolated from adult rats and cocultured with bone marrow cells. Using a rat model of doxorubicin-induced cardiomyopathy, we injected 6 × 10 5 adult cardiomyocytes, 3 × 10 7 bone marrow cells, or both into damaged hearts, for myocardial repair. Coculture of the cardiomyocytes with the bone marrow cells enhanced the expression of integrin-β1D and focal adhesion kinase in cardiomyocytes, resulting in increased survival and decreased apoptosis of the cardiomyocytes after 7 days of culture. Compared with the baseline levels, cardiac function was preserved by the implantation of bone marrow cells alone and by the implantation of cardiomyocytes in combination with bone marrow cells, but it was decreased significantly 28 days after the implantation of cardiomyocytes alone. Furthermore, apoptosis of the host cardiomyocytes was decreased significantly after the implantation of bone marrow cells alone, or in combination with cardiomyocytes, compared with that after the implantation of cardiomyocytes alone (p < 0.01). Interestingly, the implantation of adult cardiomyocytes in combination with bone marrow cells resulted in a dramatic increase in the survival of donor cardiomyocytes, and induced the myogenic differentiation of donor bone marrow stem cells. Our findings indicate that cardiomyocytes and bone marrow cells can assist and compliment each other; thus, the implantation of adult cardiomyocytes in combination with bone marrow cells shows promise as a feasible new strategy for myocardial repair.

Pre-vascularization Enhances Therapeutic Effects of Human Mesenchymal Stem Cell Sheets in Full Thickness Skin Wound Repair

“…Thus, the proliferating cells and microvessels we observed were mainly composed of rat cells. This finding is consistent with previous reports 81, 82 that the existence of hMSCs or ECs may not be necessary for the promotion of the healing process, but rather these cells appear to exert their therapeutic effects critically through the paracrine signaling molecules released by themselves 83-85. In our study, the therapeutic result of different grafts was consistent with the growth factor levels in the cell sheets, suggesting that the paracrine activity may dominate the healing process in our full thickness wound model.…”

Conditioned Medium from Hypoxic Bone Marrow-Derived Mesenchymal Stem Cells Enhances Wound Healing in Mice

“…Further support for the cell-replacement theory is afforded by the observation that BM-MSCs can migrate to sites of injury in response to chemotactic signals in vivo [4]. Nonetheless, only a small percentage of grafted BM-MSCs are actually incorporated into, and survive within lesioned tissue [5]–[6], regardless of whether the cells are locally or systemically administered. In some settings, the number of surviving BM-MSCs is, in fact, too low to explain the significant functional improvements observed following cell engraftment.…”

The Effects of Mechanical Stress on the Growth, Differentiation, and Paracrine Factor Production of Cardiac Stem Cells

“…To detect whether mechanical stress induces changes in the expression of extracellular matrix (ECM) and adhesion molecules in CDCs from both groups, we performed immunostaining with the purified rabbit anti-focal adhesion kinase (FAK) antibody (1∶25 dilution, SIGMA-ALDRICH) followed by the PE-conjugated goat anti-rabbit polyclonal second antibody (1∶1000 dilution, R&D systems), the purified rabbit anti-integrin-β 1 (1∶25 dilution, SIGMA-ALDRICH) followed by the PE-conjugated goat anti-rabbit polyclonal second antibody (1∶1000 dilution, R&D systems), the purified rabbit anti-collagen I antibody (1∶25 dilution, Abcam), followed by the Alexa Fluor®-conjugated goat anti-rabbit IgG second antibody (1∶100 dilution, Invitrogen), and the purified rabbit anti-collagen III antibody (1∶25 dilution, Abcam) , followed by the Alexa Fluor®-conjugated goat anti-rabbit IgG second antibody (1∶100 dilution, Invitrogen), after 3 days of culture [18], [23]. Cells were also stained with DAPI, and staining was examined using a fluorescence microscope equipped with a digital camera (Nikon Digital Sight DS-5Mc, JAPAN).…”