Directional transdifferentiation of bone marrow precursor cells assumes beta cell like properties in modified tissue microenvironment. The factors that modify the roles of precursor cells to functional beta cells enabling precise, defined and efficient in vitro differentiation protocols are yet to be conclusive. The study aims at the determination of appropriate induction factors that may aid the robust, reproducible transdifferentiation of rat bone marrow derived mesenchymal stem cells (MSCs) to islet-like cells and enhance their transdifferentiation efficiency. High glucose concentration including nicotinamide, β-mercaptoethanol along with β-cellulin, IGF-1 were able to induce bone marrow precursor cells to islet like clusters ex vivo consistently. The four step induction protocol has enhanced the expression of pancreatic islet cell specific transcription and translational factors detectable by immunocytochemistry viz., pro-insulin, glucagon, somatostatin and polypeptide. The functionality was assessed by the glucose challenge assay followed by animal experiment. The streptozotocin (STZ) induced rats demonstrated significant reduction in glucose levels post islet like cell transplantation (P<0.05). The tropic and the growth factors thus used have a profound impact on the induction of the bone marrow precursors to functional islet like cells
The perivascular epithelioid cell tumor (PEComa) family of tumors includes angiomyolipoma, lymphangioleiomyomatosis, clear cell sugar tumor of the lung, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and rare clear cell tumors of other anatomical sites (PEComas-NOS). Among the PEComas-NOS, pigmented variants are extremely rare. The case concerns a 50-year-old female who presented with pain in right hypochondrium. The resected specimen included a 24 × 18 × 9 cm mass. The tumor was histologically characterized by both spindle and epithelioid cells with round to oval nuclei and clear to eosinophilic cytoplasm containing abundant melanin pigment. The stroma demonstrated intervening, thin, fibrovascular septa. Immunohistochemically, the tumor cells were strongly positive for HMB-45, weak positive for smooth muscle actin (SMA), and negative for Hep Par 1, Glypican 3, MUM-1, and S-100 protein. The patient had no evidence of disease 24 months after surgery. Pathologists and clinicians should know about the existence of pigmented perivascular epithelioid cell tumor of the liver.
Fluorescent magnetic iron oxide nanoparticles have been used to label cells for imaging as well as for therapeutic purposes. The purpose of this study was to modify the approach to develop a nanoprobe for cell selection and imaging with a direct therapeutic translational focus. The approach involves physical coincubation and adsorption of superparamagnetic iron oxide nanoparticle-polyethylene glycol (SPION-PEG) complexes with a monoclonal antibody (mAb) or a set of antibodies. Flow cytometry, confocal laser scanning microscopy, transmission electron microscopy, iron staining, and magnetic resonance imaging were used to assess cell viability, function, and labeling efficiency. This process has been validated by selecting adipose tissue-derived cardiac progenitor cells from the stromal vascular fraction using signal regulatory protein alpha (SIRPA)/kinase domain receptor (KDR) mAbs. These markers were chosen because of their sustained expression during cardiomyocyte differentiation. Sorting of cells positive for SIRPA and KDR allowed the enrichment of cardiac progenitors with 90% troponin-I positivity in differentiation cultures. SPION labeled cardiac progenitor cells (1×10 5 cells) was mixed with gel and used for 3T magnetic resonance imaging at a concentration, as low as 12.5 μg of iron. The toxicity assays, at cellular and molecular levels, did not show any detrimental effects of SPION. Our study has the potential to achieve moderate to high specific cell selection for the dual purpose of imaging and therapy.
There is an increasing evidence suggesting the role of fork head boxP3 (FoxP3) in the development and the regulation of CD4+CD25+ Treg cells. T-cell regulatory mechanisms in rheumatoid arthritis patients were evaluated by the contributing factors such as pro-inflammatory cytokines, circulating immune complexes, HLA DR expression, ligand binding biomarkers, FoxP3 expression in paired samples of peripheral blood (PB) and synovial fluid (SF). These cellular responses were further correlated with the humoral immune responses such as anti-cyclic citrullinated peptides IgG (CCP), circulating immune complex-c1q IgG (CIC), immunoglobulin G (IgG) and immunoglobulin M (IgM) of the rheumatoid arthritis factor (RAF). The results suggest a definitive role of Tregs in the homeostatic control because there is an increase in FoxP3 (37%) and HLA-DR (45%) expression in the synovial fluid as compared to PB. Furthermore, humoral responses as a downstream effector mechanism are positively correlated with the pathogenesis of rheumatoid arthritis (RA). A positive relationship exists between quantitative anti-CCP production and the expression of HLA-DR. The study relates an increased and pivotal role of B cell activation in the synovial fluid thereby permitting the need to ablate the targeted B cell immune responses.
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