Dr.Sethu Lekshmy Nair C - Academia.edu (original) (raw)

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Papers by Dr.Sethu Lekshmy Nair C

Journal of Heart and Lung Transplantation, Apr 1, 2012

Blood, 2011

896 Sickle cell disease (SCD) is a devastating hemolytic disease characterized by recurring episo... more 896 Sickle cell disease (SCD) is a devastating hemolytic disease characterized by recurring episodes of painful vaso-occlusive crises and endothelial dysfunction. We hypothesize that hemoglobin (Hb) or hemin (ferri-protoporphyrin IX), released from HbS derived from hemolyzed sickle red blood cells, is fundamental to vaso-occlusion and vasculopathy in SCD. Utilizing intravital microscopy and dorsal skin fold chambers implanted on mice we previously demonstrated transient stasis in subcutaneous venules in response to hypoxia in transgenic sickle, but not normal mice. In the current studies we used NY1DD sickle mice; Townes-AA, -AS, and -SS mice; and C57 normal mice to test whether Hb or heme induce vaso-occlusion in the absence of a hypoxic stimulus. Four groups of 3–6 mice were given a bolus infusion (0.012 ml/g i.v.) of the following: 1) saline; 2) stroma-free HbA (32 umols heme/kg); 3) hemin (32 umols/kg); or 4) water (to induce intravascular hemolysis). In NY1DD mice, Hb, hemin or...

Translational Research, 2019

We have investigated a unique cell type, blood outgrowth endothelial cells (BOEC), as a cell-base... more We have investigated a unique cell type, blood outgrowth endothelial cells (BOEC), as a cell-based gene therapy approach to pulmonary hypertension. BOEC are bona fide endothelial cells, obtained from peripheral blood, that can be expanded to vast numbers, and are amenable to both cryopreservation and genetic modification. We established primary cultures of rat BOEC and genetically altered them to over-express human eNOS plus green fluorescent protein (rBOEC/eNOS) or to express GFP only (rBOEC/GFP). We gave monocrotalineD 1 7 X X to rats on day 0, and they developed severe pulmonary hypertension. As a Prevention model, we infused saline or rBOEC/GFP or rBOEC/eNOS on day 3, and then examined endpoints on day 24. The rBOEC/eNOS recipients developed elevated NOx (serum and lung) and less severe: elevation of right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and pulmonary arteriolar muscularization and loss of alveolar density. As an Intervention model, we waited until day 21 to give the test infusions, and we examined endpoints on day 35. The rBOEC/eNOS recipients again developed elevated NOx and manifested the same improvements. Indeed, rBOEC/eNOS infusion not only prevented worsening of RVSP but also partially reversed established arteriolar muscularization. These data suggest that BOEC may be useful as a carrier cell for genetic strategies targeting pulmonary hypertension. Their properties render BOEC amenable to preclinical and scale-up studies, available for autologous therapies, and tolerant of modification and storage for potential future use in patients at risk for PAH, eg, as defined by genetics or medical condition.

International Journal of Biological Macromolecules, 2013

In this work, the attachment, viability and functionality of rat Blood Outgrowth Endothelial Cell... more In this work, the attachment, viability and functionality of rat Blood Outgrowth Endothelial Cells (rBOEC) and genetically modified rBOEC (rBOEC/eNOS-GFP), which over express endothelial nitric oxide synthase (eNOS), were investigated on Poly(lactic acid) (PLA)-chitosan and PLA-chitosan-collagen nanofibrous scaffolds. Both the cell types displayed good attachment, remained viable and functional on both scaffolds. Moreover, incorporation of collagen in the scaffold helped in sustaining the rBOEC for upto one week, although collagen was not found necessary for rBOEC/eNOS-GFP. We conclude that PLA-chitosan based nanofibrous scaffolds can be a potential candidate for BOEC based wound healing applications.

Experimental Hematology, 2012

The goal of this study was to determine if we could establish a mesenchymal stromal line from zeb... more The goal of this study was to determine if we could establish a mesenchymal stromal line from zebrafish that would support hematopoietic cells. Such a coculture system would be a great benefit to study of the hematopoietic cellLstromal cell interaction in both in vitro and in vivo environments. Zebrafish stromal cells (ZStrC) were isolated from the ''mesenchymal'' tissue of the caudal tail and expanded in a specialized growth media. ZStrC were evaluated for phenotype, gene expression, and ability to maintain zebrafish marrow cells in coculture experiments. ZStrC showed mesenchymal and endothelial gene expression. Although ZStrC lacked the ability to differentiate into classic mesenchymal stromal cell lineages (i.e., osteocytes, adipocytes, chondrocytes), they did have the capacity for endotube formation on Matrigel and lowdensity lipoprotein uptake. ZStrC supported marrow cells for O2 weeks in vitro. Importantly, marrow cells were shown to retain homing ability in adoptive transfer experiments. ZStrC were also shown to improve hematopoietic recovery after sublethal irradiation after adoptive transfer. As the zebrafish model grows in popularity and importance in the study of hematopoiesis, new tools to aid in our understanding of the hematopoietic cellLstromal cell interaction are required. ZStrC represent an additional tool in the study of hematopoiesis and will be useful in understanding the factors that mediate the stromal cellLhematopoietic cell interactions that are important in hematopoietic cell maintenance.