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Adult BM stem cells are being investigated for their potential to regenerate injured tissues by a process referred to as plasticity or transdifferentiation. Although data supporting stem cell plasticity is extensive, a controversy has emerged based on findings that propose cell-cell fusion as a more appropriate interpretation for this phenomenon. A major focus of this controversy is the claim that acutely infarcted myocardium in adult hearts can be regenerated by BM stem cells. Many researchers consider the adult heart to be a post-mitotic organ, whereas others believe that a low level of cardiomyocyte renewal occurs throughout life. If renewal occurs, it may be in response to cardiac stem cell activity or to stem cells that migrate from distant tissues. Post-mortem microscopic analysis of experimentally induced myocardial infarctions in several rodent models suggests that cardiomyocyte renewal is achieved by stem cells that infiltrate the damaged tissue. For a better understanding of the possible involvement of stem cells in myocardial regeneration, it is important to develop appropriate technologies to monitor myocardial repair over time with an emphasis on large animal models. Studies on non-human primate, swine and canine models of acute myocardial infarctions would enable investigators to utilize clinical quality cell-delivery devices, track labeled donor cells after precision transplantation and utilize non-invasive imaging for functional assays over time with clinical accuracy. In addition, if stem cell plasticity is to reach the next level of acceptance, it is important to identify the environmental cues needed for stem cell trafficking and to define the genetic and cellular mechanisms that initiate transdifferentiation. Only then will it be possible to determine if, and to what extent, BM stem cells are involved in myocardial regeneration and to begin to regulate precisely tissue repair. [ABSTRACT FROM AUTHOR]

Presents information on the short-term and long-term reconstituting stem cells in mouse myocardium. Developmental potential of stem cells that emerge during late embryonic and fetal development; Reconstitution of the entire hematopoietic system; Overview of myocardial infarction in hear disease.

Hematopoietic stem cells (HSC) from bone marrow, peripheral blood and cord blood are important in clinical transplantation. However, their use in gene therapy protocols is still limited by a low level of transduction efficiency. In addition to the cell cycling block to retrovirus transduction, we recently demonstrated that the low level of retrovirus receptor mRNA in mouse HSC correlated with the low level of amphotropic retrovirus transduction in these cells. Similarly, we found low levels of mRNA encoding the amphotropic retrovirus receptor in human bone marrow Lin CD34+ CD38- HSC. In an effort to identify an alternative population of human HSC that might be more efficiently transduced, we assayed HSC populations from cord blood for mRNA encoding the amphotropic retrovirus receptor. High levels of receptor mRNA were present in HSC from previously cryopreserved cord blood compared with HSC from fresh bone marrow and fresh cord blood. The HSC from cryopreserved cord blood are excellent candidates for gene therapy protocols. [ABSTRACT FROM AUTHOR]

Objective: Drug eluting stents have been shown to reduce the rate of in-stent reslenosis in cases where single lesions are treated. The performance of these stents, in patients with multivessel disease and complex lesions, however, remains unknown. Our experience with sirolimus eluting stents in such patients is presented. Design and patients: This study includes all consecutive patients treated at San Raffaele Hospital and EMO Centro Cuore Columbus, Milan, Italy treated with sirolimus eluting stents. Results: Between April 2002 and March 2003, 486 patients with 1027 lesions were treated (437 males, 49 females) with a mean (SD) age of 62.2 (10.5) years. Of all patients studied, 19.1 % had single vessel disease, 33.8% had two vessel disease, and 47.1 % had three vessel disease. Of the whole study group, 20.3% of patients had diabetes mellitus. A mean (SD) of 2.3 (0.4) stents per patient and 1.1(0.2) stents per lesion were implanted. The baseline mean reference diameter was 2.7(0.6) mm with a mean minimal luminal diameter of 0.9 (0.5) mm. Post-stenting, the acute gain was 1 .8 (0.6) mm. During hospital stay one patient died (0.2%) and 13 (2.7%) patients had in-hospital myocardial infarction (MI). One patient required urgent repeat percutaneous coronary intervention. Six months clinical follow up was performed in all 347 eligible patients. Six months mortality was 2.0% (n = 7) and acute MI occurred in 0.3% (n = 1). Target lesion revascularisation occurred in 95% (n = 33) of the patients and target vessel revascularisation (1VR) in 11.5% (n = 40) of the patients. Major adverse cardiac event rate was 13.8% (n = 48). TVR was 4.5% For single vessel disease and 13.2% for multivessel disease. Diabetes mellitus was the only significant predictor for D/R. Conclusion: The use of drug eluting stents in single and multivessel coronary disease produces good short and medium term results with a low rate of revascularisation. Longer term follow-up is required to confirm these observations. [ABSTRACT FROM AUTHOR]

The transduction efficiencies of immunoselected rhesus macaque (Macaca mulatta) CD34+ cells and colony- forming progenitor cells based on polymerase chain reaction (PCR) analysis were comparable for an amphotropic Moloney murine leukemia virus (MLV) retroviral vector and a retroviral vector derived from the gibbon ape leukemia virus (GaLV) packaging cell line, PG13. On performing autologous transplantation studies using immunoselected CD34+ cells transduced with the GaLV envelope (env) retroviral vector, less than 1% of peripheral blood (PB) contained provirus. This was true whether bone marrow (BM) or cytokine-mobilized PB immunoselected CD34+ cells were reinfused. This level of marking was evident in two animals whose platelet counts never fell below 50000/μl and whose leukocyte counts had recovered by days 8 and 10 after having received 1.7 × 107 or greater of cytokine-mobilized CD34+ PB cells/kg. Reverse transcriptase(RT)-PCR analysis of CD34+ subsets for both the GaLV and amphotropic receptor were performed. The expression of the GaLV receptor was determined to be restricted to CD34+ Thy-1+ cells, and both CD34+ CD38+ and CD34+ CD38dim cells, while the amphotropic receptor was present on all CD34+ cell subsets examined. Our findings suggest that, in rhesus macaques, PG13-derived retroviral vectors may only be able to transduce a subset of CD34+ cells as only CD34+Thy-1+ cells express the GaLV receptor. [ABSTRACT FROM AUTHOR]

Purpose: Despite the fact that techniques for recanalization of chronic total occlusions (CTO) are improved, the benefit of successful recanalization of the artery remains unclear. The aim of our study is to determine the success rate of percutaneous procedures and to evaluate the event free long-term survival in patients with CTO who underwent percutaneous coronary intervention (PCI).Methods: Our study included 283 consecutive patients with chronic total occlusions who underwent percutaneous coronary intervention on CTO at Clinic for Cardiology, between Jan 1st 2009 and Dec 31st 2010. Data were obtained retrospectively from Cath lab database at Clinic for Cardiology. Follow up data were obtained by direct phone contact.Results: Overall procedural success was achieved in 62.3% interventions. Independent predictors for procedural failure were presence of vessel tortuosity (P=0.007), vessel wall calcifications (P=0.000), blunt stump (P=0.000) and unstable angina pectoris as negative predictor (P=0.009). Overall MACE rates were similar in the procedural success and procedural failure groups (10% vs. 12.8%, p=0.455). There was no significant difference in the event free survival rate between success and failure group (89.8% vs. 87.2%, Log-Rank =0.468, p=0.494).Conclusions: Our study demonstrated that success rate of PCI in patients with CTO is acceptable and safe. Nevertheless, successful recanalization of CTO was not associated with an improved event free survival. [ABSTRACT FROM AUTHOR]