NOVEL APPROACH FOR EX-VIVO EXPANSION OF HEMATOPOIETIC STEM CELLS USING DECELLULARIZED HUMAN UMBILICAL CORD EXTRACTS

Abstract

Hematopoietic stem cell transplantations (HSCT) represent so far, the only efficient reconstructive tool for damaged bone marrow (BM) in hematological disorders. The success of these regenerative strategies relies on the hematopoietic stem cells’ (HSC) availability, quality, stemness, and potency. Many constraints can hinder these therapies whether through the limited success in the ex-vivo expansion of HSCs, their different sources, or their substandard engraftment outcomes, which ultimately restrain HSCs from reaching their utmost clinical therapeutic potential. The central hub of adult HSCs, the BM niche, compartmentalizes supporting cells, the extracellular matrix (ECM), and soluble factors which collectively dictate the fate of HSCs. For this reason, recent investigations have relied on the application of umbilical cord-derived ECM (UC-ECM) as an alternative source to expand HSCs, owing to their similarities with BM-ECM in their biochemical composition, their ease of accessibility as biological leftovers, and their ability to surpass ethical concerns. Hence, our study is focused on establishing a multifaceted culture system comprised of mobilized peripheral blood-derived HSCs, seeded on BM-derived MSCs (BM-MSC) supporting monolayer, both of which are supported by decellularized UC-derived ECM. Therefore, by remaining faithful to the native HSC milieu, we have successfully established a BM mimetic culture system that supports the survival and maintenance of CD34+ HSCs. We have found that UC-ECM-treated BM-MSC monolayers create an in-vivo mimicry microenvironment that aids in preserving CD34+ HSC stemness. Thus, our culture system employs low-cost, easily accessible, biocompatible, and biochemically active scaffold material capable of competing with the modern, highly complex, and expensive expansion strategies that can ultimately serve the uprise of regenerative therapies for BM regeneration.