Cellular therapy is reaching a pinnacle with an understanding of the potential of human mesenchymal stem cells (hMSCs) to regenerate damaged tissue in the body. The limited numbers of these hMSCs in currently identified sources, like bone marrow, adipose tissue, and so forth, bring forth the need for their
in vitro culture/expansion. However, the extensive usage of supplements containing xenogeneic components in the expansion-media might pose a risk to the post-transplantation safety of patients. This warrants the necessity to identify and develop chemically defined or “humanized” supplements which would make
in vitro cultured/processed cells relatively safer for transplantation in regenerative medicine. In this paper, we outline the various caveats associated with conventionally used supplements of xenogenic origin and also portray the possible alternatives/additives which could one day herald the dawn of a new era in the translation of
in vitro cultured cells to therapeutic interventions.
Mesenchymal stem cell (MSC)-based liver tissue engineering on nanofibrous scaffold holds great promise for cell-based therapy in liver injuries and end-stage liver failure treatments. We investigated the hepatic trans-differentiation potential of human MSCs on a biocomposite poly(L-lactic acid)-co-poly (3-caprolactone)/collagen (PLACL/collagen) nanofibrous scaffold. The nanofibrous scaffolds comprised of PLACL, collagen and a PLACL/collagen blend (2 : 1) were fabricated by electrospinning and also evaluated for fiber morphology, surface wettability, functional groups, porosity and tensile properties.Hepatic trans-differentiation of human bone marrow-derived MSCs (hMSCs) was carried out on these scaffolds over a period of 28 days using sequential induction with hepatogenic growth factors.Hepatogenesis was confirmed by scanning electron microscopy (SEM), cell phenotype tracking dye expression, quantitative expression of hepatic genes, immunofluorescence staining of hepatocyte-specific markers and albumin release. The results proved that the porous PLACL/collagen nanofibrous scaffold supported enhanced hMSC proliferation and hepatic trans-differentiation compared to individual PLACL and collagen scaffolds as well as a monolayer culture on tissue culture plate (TCP). Interestingly, hMSCderived hepatocyte-like cells on PLACL/collagen nanofibrous scaffolds could aggregate to form functional 'hepatospheres' similar to normal hepatic spheroids. The present study concludes that PLACL/ collagen nanofibrous scaffolds are potentially biomimetic and upon sequential induction with hepatogenic growth factors/cytokines, it augments trans-differentiation of hMSCs towards functional hepatosphere formation. Such bioengineered nanofibrous scaffold hepatic construct provides a promising approach for cellular therapy of damaged livers in end-stage liver failure treatments.
The results of our analysis suggest that patients with pSS have a 12% prevalence of OLAIE with a wide range (7.3-21.2%) found between practices. This difference is likely related to the different screening protocols for oral dryness between sites.
Establishment of non-invasive urinary biomarker for the early prediction of essential hypertension (EH) is important. We evaluated whether estimation of urinary DNA, serves as a marker to predict the extent of cellular oxidative stress in essential hypertension. A total of 180 South Indian subjects aged 30-65 were recruited for the study. Of these hypertensive subjects investigated, 30 were newly diagnosed and were not on any antihypertensive drugs, but had systolic blood pressure 140-160 mmHg and diastolic blood pressure 95-100 mmHg and 75 hypertensive patients who already on drug therapy for one year and 75 were South Indian normotensive healthy controls with blood pressure ≤ 120/80 mmHg. The 8-OHdG level in urine was significantly increased in hypertensive patients (both newly diagnosed and who already on drug therapy) compared with control group. The significant increase in 8-OHdG was observed in newly diagnosed hypertensive patients compared with hypertensive patients who already on drug therapy. There was a significant decrease in serum TAS value in essential hypertensive group when compared to control group. The urinary 8-OHdG was independently correlated with serum TAS. Decreased TAS levels, which reflect to increased oxidative stress, may be the reason of increased urinary 8-OHdG in South Indian hypertensive patients. Our preliminary data suggest that the competitive ELISA for 8-OHdG appears to be a simple method for quantifying the extent of oxidative stress.
Coronary artery fistulae are rare anomalies encountered in 0.1-0.2% of angiographic series. We recently encountered a patient evaluated for mitral valve disease who incidentally had bilateral coronary artery fistulae detected on preoperative angiogram. These fistulae drained into the pulmonary artery. She underwent successful transpulmonary closure of the fistula along with mitral valve repair. We discuss the embryological basis of this anomaly and the clinical as well as surgical significance.
Design and development of ex vivo bioengineered liver tissue substitutes intended for subsequent in vivo implantation has been considered therapeutically relevant to treat many liver diseases that require whole-organ replacement on a long-term basis. The present study focus on patient-inspired ex vivo liver tissue engineering strategy to generate hepatocyte-scaffold composite by combining bone marrow mesenchymal stem cells (BMSCs) derived from cardiac failure patients with secondary hyperbilirubinemia as primers of hepatic differentiation and hepatocyte growth factor (HGF)-enriched sera from same individuals as hepatic inducer. A biodegradable and implantable electrospun fibrous mesh of poly-l-lactic acid (PLLA) and gelatin is used as supporting matrix (average fiber diameter = 285 ± 64 nm, porosity = 81 ± 4%, and average pore size = 1.65 ± 0.77 μm). The fibrous mesh supports adhesion, proliferation, and hepatic commitment of patient-derived BMSCs of adequate stemness using HGF-enriched sera generating metabolically competent hepatocyte-like cells, which is comparable to the hepatic induction with defined recombinant growth factor cocktail. The observed results confirm the combinatorial effects of nanofiber topography and biochemical cues in guiding hepatic specification of BMSCs. The fibrous mesh-hepatocyte construct developed in this study using natural growth factors and BMSCs of same individual is promising for future therapeutic applications in treating damaged livers.
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