Harnessing 3D models of the bone marrow to study cellular interactions in hematopoietic stem cell niches

Abstract text (incl. figure legends and references)

Introduction

Bone marrow is the site of hematopoiesis, the process in which hematopoietic stem cells (HSCs) replenish the body with fresh blood cells. For this purpose, HSCs are tightly regulated by their direct microenvironment in so-called stem cell niches. These niches are formed by supporting niche cells, the extracellular matrix and soluble factors. Efficient communication between the different niche components is crucial to maintain niche functionality.

Objectives

Using 3D models of the bone marrow, we aim to investigate the interplay of hematopoietic stem and progenitor cells (HSPCs) with different niche components in health and disease.

Materials and Methods

Applying macroporous hydrogels, 3D cultures mimicking HSPC niches in healthy and diseased bone marrow were developed and used to investigate cellular interactions.

Results

We could show that there is a mutual interplay between HSPCs and their microenvironment. Thus, not only the niche controls HSPC behavior, but also the HSPCs shape their microenvironment. This interplay is important for physiological HSPC function as well as pathological processes such as bone metastasis.

Conclusion

3D models of the bone marrow allow fundamental studies of reciprocal cellular relationships in the human HSPC niche.