Clinical evidence suggests that intramyocardial bone marrow stem cell transplantation in combination with coronary artery bypass grafting is associated with improvements of functional parameters in patients with chronic ischemic heart disease. Furthermore, surgical intramyocardial bone marrow stem cell transplantation seems to be safe.

In the era of intravascular approaches for regenerative cell therapy, the underlying mechanisms of stem cell migration to non-marrow tissue have not been clarified. We hypothesized that next to a local inflammatory response implying adhesion molecule expression, endothelial nitric oxide synthase (eNOS)-dependent signaling is required for stromalcell-derived factor-1 alpha (SDF-1a)-induced adhesion of c-kit þ cells to the vascular endothelium. SDF-1a/tumor necrosis factor-alpha (TNF-a)-induced c-kit þ -cell shape change and migration capacity was studied in vitro using immunohistochemistry and Boyden chamber assays. In vivo interaction of c-kit þ cells from bone marrow with the endothelium in response to SDF-1a/TNF-a stimulation was visualized in the cremaster muscle microcirculation of wild-type (WT) and eNOS (À/À) mice using intravital fluorescence microscopy. In addition, NOS activity was inhibited with N-nitro-Larginine-methylester-hydrochloride in WT mice. To reveal c-kit þ -specific adhesion behavior, endogenous leukocytes (EL) and c-kit þ cells from peripheral blood served as control. Moreover, intercellular adhesion molecule-1 (ICAM-1) and CXCR4 were blocked systemically to determine their role in inflammation-related c-kit þ -cell adhesion. In vitro, SDF-1a enhanced c-kit þ -cell migration. In vivo, SDF-1a alone triggered endothelial rolling-not firm adherence-of c-kit þ cells in WT mice. While TNF-a alone had little effect on adhesion of c-kit þ cells, it induced maximum endothelial EL adherence. However, after combined treatment with SDF-1a þ TNF-a, endothelial adhesion of c-kit þ cells increased independent of their origin, while EL adhesion was not further incremented. Systemic treatment with anti-ICAM-1 and anti-CXCR4-monoclonal antibody completely abolished endothelial c-kit þ -cell adhesion. In N-nitro-L-arginine-methylester-hydrochloride-treated WT mice as well as in eNOS (À/À) mice, firm endothelial adhesion of c-kit þ cells was entirely abrogated, while EL adhesion was significantly increased. The chemokine SDF-1a mediates firm adhesion c-kit þ cells only in the presence of TNF-a stimulation via an ICAM-1-and CXCR4-dependent mechanism. The presence of eNOS appears to be a crucial and specific factor for firm c-kit þ -cell adhesion to the vascular endothelium.

Intramyocardial stem cell therapy was safe but lacked significant lasting benefits beyond 6 months in our study cohort with a limited number of patients. Preoperative left ventricular ejection fraction and time since myocardial infarction may be critical parameters for selection of patients who can benefit most from intramyocardial stem cell treatment during coronary artery bypass grafting.

Orthogonal polarization spectral imaging data reveal an impairment of microvascular perfusion during on-pump CABG. Changes in FCD indicate a faster recovery of the microvascular perfusion in MECC during the reperfusion period. Beneficial recovery of microvascular organ perfusion could partly explain the perioperative advantages reported for MECC.

SC+F serves as an excellent autologous matrix for intraoperative tissue engineering of valve prostheses promising optimal in vivo integration. However, stability remains an issue.