An ECM-based model derived from DWJM to study hematopoiesis and leukemia

Abstract

Hematopoietic stem cells (HSCs) are responsible for the generation of the body’s whole blood and immune cells. This process occurs mainly within the bone marrow microenvironment, known as the "niche", which provides signals to regulate HSC survival, quiescence, self-renewal, and differentiation. This niche microenvironment is comprised of cellular components, extracellular matrix (ECM), and soluble cytokines and growth factors. Although the understanding of these signals is growing, there is still no well-established in vitro system to study the role of these signals in hematopoiesis; such knowledge could be utilized to expand HSCs for clinical use. In addition, a growing number of studies have shown that alteration of the bone marrow niche is associated with leukemia resistance and progression. Here we used decellularized Wharton's jelly matrix (DWJM), the ECM part of umbilical cord, as a scaffold to engineer a hematopoietic niche for normal and malignant hematopoiesis. The findings that DWJM prevents the loss of hematopoietic stem cell characteristics and that it enriches a leukemia stem cell (LSC) – like population indicate that this natural ECM biomaterial is a suitable in vitro model of the bone marrow microenvironment that could be utilized to expand HSPCs (hematopoietic stem and progenitor cells) and to provide a potential platform to study the effects of niche components on hematopoiesis and leukemia.