Yogesh Kumar Verma
Institute of Nuclear Medicine and Allied Sciences, DRDO, India
Title: Receptor masking bax antagonism and licl supplementation improves homing and engraftment of bone marrow cells
Biography
Biography: Yogesh Kumar Verma
Abstract
Effective homing of stem cells is a pre-requisite for successful hematopoietic stem cell transplantation (HCT) when there is a dearth of available hematopoietic stem cells (HSC). However, the transplanted cells face premature differentiation and death while en route to bone marrow. This causes decreased engraftment of transplanted HSC. In order to enhance the homing of stem cells to bone marrow as undifferentiated cells, in this study the mouse bone marrow cells were masked with fibronectin modified alginate (A-F). This biocompatible coat prevented the antibody from binding to its cognate receptor, i.e. CD49e, which is present on the cell surface. In addition, coating effectively abolished RBC’s clumping by reactive antibodies in haemagglutination assay. Bioluminescence imaging showed significant improvement in the efficiency of coated cells to home in bone marrow. This also provided protection to irradiated BALB/c mice (75% on sublethal irradiation). To further enhance the transplantation efficiency, we designed and evaluated Bax antagonist peptide (BAP-GR23) for decreasing the death of HSC and other tissues, which become morbid on preparatory or undesired radiation exposure. We found that administration of novel BAP and LiCl combination followed by A-F coated bone marrow cells transplantation and ascorbic acid supplementation Ad libitum was effective in preventing the imminent death of lethally irradiated BALB/c mice (100% survival). Radiation-induced aplasia was corrected after 10days of treatment. Histologically no toxicity of the treatment was observed. This combination also improved survivability and clonogenicity of cells with a concomitant decrease in DNA degradation in the comet assay. Microarray data analysis showed a specific role of LiCl in upregulation of cell survival genes’ expression along with downregulation of bile producing genes (CYP7A1 and FOXA2) having a role in radiation-induced gastrointestinal syndrome. These results suggest the development of a new multi-therapy paradigm to enhance the clinical efficacy of HCT.