cells, that expressed EGFP in the cardiomyocyte-specific manner were transplanted directly into BM of lethally irradiated mice, MI was induced, and they were treated with G-CSF. EGFP ؉ actinin ؉ cells were observed in the ischemic myocardium, indicating that CMG cells had been mobilized and differentiated into cardiomyocytes. Together, these results suggest that the origin of the vast majority of BM-derived cardiomyocytes is MSCs.
The longer OS at 3 years and higher CR rate with VCAP-AMP-VECP compared with biweekly CHOP suggest that VCAP-AMP-VECP might be a more effective regimen at the expense of higher toxicities, providing the basis for future investigations in the treatment of ATLL.
Putative myogenic and endothelial (myo-endothelial) cell progenitors were identified in the interstitial spaces of murine skeletal muscle by immunohistochemistry and immunoelectron microscopy using CD34 antigen. Enzymatically isolated cells were characterized by fluorescence-activated cell sorting on the basis of cell surface antigen expression, and were sorted as a CD34+ and CD45− fraction. Cells in this fraction were ∼94% positive for Sca-1, and mostly negative (<3% positive) for CD14, 31, 49, 144, c-kit, and FLK-1. The CD34+/45− cells formed colonies in clonal cell cultures and colony-forming units displayed the potential to differentiate into adipocytes, endothelial, and myogenic cells. The CD34+/45− cells fully differentiated into vascular endothelial cells and skeletal muscle fibers in vivo after transplantation. Immediately after sorting, CD34+/45− cells expressed only c-met mRNA, and did not express any other myogenic cell-related markers such as MyoD, myf-5, myf-6, myogenin, M-cadherin, Pax-3, and Pax-7. However, after 3 d of culture, these cells expressed mRNA for all myogenic markers. CD34+/45− cells were distinct from satellite cells, as they expressed Bcrp1/ABCG2 gene mRNA (Zhou et al., 2001). These findings suggest that myo-endothelial progenitors reside in the interstitial spaces of mammalian skeletal muscles, and that they can potentially contribute to postnatal skeletal muscle growth.
Concurrent chemoradiotherapy using multidrug resistance-nonrelated agents and etoposide is a safe and effective treatment for localized nasal NK/T-cell lymphoma and warrants further investigation.
Summary. This phase II trial was performed to evaluate the efficacy of a new granulocyte colony-stimulating factor (G-CSF)-supported multi-agent chemotherapy protocol, LSG15, for aggressive adult T-cell leukaemia-lymphoma (ATL). Ninety-six previously untreated patients with aggressive ATL were enrolled and grouped as: acute type (58), lymphoma type (28) and unfavourable chronic type (10). Therapy consisted of seven cycles of VCAP (vincristine, cyclophosphamide, doxorubicin and prednisone), AMP (doxorubicin, ranimustine and prednisone) and VECP (vindesine, etoposide, carboplatin and prednisone). G-CSF was administered during the intervals between chemotherapy until neutrophil reconstitution was achieved. Eighty-one per cent of the 93 eligible patients responded [95% confidence interval (CI), 71´1±88´1%], with 33 patients obtaining complete response (35´5%) and 42 obtaining partial response (45´2%). The median survival time (MST) after registration was 13 months and the median follow-up duration of the 20 surviving patients was 4´2 years (range 2´8±5´6). Overall survival at 2 years was estimated to be 31´3% (95% CI, 22´0±40´5%). Grade 4 haematological toxicity of neutropenia and thrombocytopenia were observed in 65´3% and 52´6% of the patients respectively, but grade 4 non-haematological toxicity was observed in only one patient. LSG15 is feasible with mild non-haematological toxicity and improved the clinical outcome of ATL patients. MST and overall survival at 2 years were superior to those obtained by our previous trials.
MSCs transplanted to degenerative discs in rabbits proliferated and differentiated into cells expressing some of the major phenotypic characteristics of nucleus pulposus cells, suggesting that these MSCs may have undergone site-dependent differentiation. Further studies are needed to evaluate their functional role.
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