Abstract
Hematopoietic stem cells (HSC) are responsible for the production of blood and immune cells during life. HSC fate decisions are dependent on signals from specialized microenvironments in the bone marrow, termed niches. The HSC niche is a tridimensional environment that comprises cellular, chemical, and physical elements. Introductorily, we will revise the current knowledge of some relevant elements of the niche. Despite the importance of the niche in HSC function, most experimental approaches to study human HSCs use bidimensional models. Probably, this contributes to the failure in translating many in vitro findings into a clinical setting. Recreating the complexity of the bone marrow microenvironment in vitro would provide a powerful tool to achieve in vitro production of HSCs for transplantation, develop more effective therapies for hematologic malignancies and provide deeper insight into the HSC niche. We previously demonstrated that an optimized decellularization method can preserve with striking detail the ECM architecture of the bone marrow niche and support HSC culture. We will discuss the potential of this decellularized scaffold as HSC niche model. Besides decellularized scaffolds, several other methods have been reported to mimic some characteristics of the HSC niche. In this review, we will examine these models and their applications, advantages, and limitations.
Highlights
Hematopoietic stem cells (HSC) are rare, self-renewing, multipotent cells that are responsible for maintaining the blood and immune cells supply through a process called hematopoiesis
mesenchymal stem cells (MSC) were encapsulated in collagen microspheres, osteogenic differentiation was induced and subsequent decellularization to use it as scaffold for HSCs culture
Culture of stromal cells in some scaffolds induce the production of extracellular matrix (ECM) elements that mimic the natural niche matrix [18,61,62,68,91], and this functionalization contribute to adhesion and natural responses in HSCs
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. A population of self-renewing HSCs remain in a quiescent state, protected from genotoxic insults and exhaustion [5], while committed progenitors mobilize to other niches and into circulation [1] This balance of differentiation and quiescence is essential to maintain homeostasis and health. HSCs are probably the most clinically used adult stem cells These primitive progenitors are responsible for the reconstitution of the hematopoietic system upon bone marrow ablation and transplantation [6]. Despite advances in the understanding of the role of the functional and structural components of the HSC niche, there is no ex vivo model that can faithfully reproduce the in vivo HSC niche homeostasis, long-term stem cell maintenance and complex cellular interactions of the niche. We will overview the current knowledge of elements of the HSC niche and describe up-to-date 3D culture HSC niche models
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