Abstract

Hematopoietic stem and progenitor cells (HSPCs) are the key regulators of hematopoiesis which give rise to different, mature, and committed lineages. Exposure to acute whole-body radiation results in the loss of HSPCs leading to the inability of the system to generate differentiated lineages which ultimately cause a hematopoietic form of acute radiation syndrome (hs-ARS). Currently, no safe and effective molecule as a radiation countermeasure is available for human applications. Due to this bone marrow transplantation (BMT) has become an indispensable strategy for the management of radiation over-exposed victims, hematopoietic malignancies, and planned chemotherapy-induced bone marrow depression. Several strategies have been employed to achieve successful Hematopoietic stem cell transplantation (HSCT), capable of enhancing HSC homing and engraftment potential but at a high cost. Here in this study, we have reported an inexpensive strategy involving short-term ex-vivo exposure of bone marrow mononuclear cells (BMMNCs) to a small molecule that successfully enhances the HSPCs proliferation, migration, and home to its BM niche after transplantation. Results indicate that ex-vivo exposure led to a significant increase in CXCR4 expression and migration of HSPCs towards SDF-1α as evident from in-vitro studies. In-vivo data displayed that ex-vivo exposure of BMMNCs with the molecule resulted in a significant increase in the number of homed cells to the BM niche as compared to the vehicle-treated group. Hence, the above strategy suggests an efficient and cost-effective method for achieving successful HSC transplantation for a variety of scenarios including management of hs-ARS.