# 3D In Vitro Models of the Bone Marrow Niche

## TL;DR

This review discusses how 3D in vitro models of the bone marrow niche improve understanding of blood cell development and drug testing.

## Contribution

The paper provides a comprehensive review of advanced 3D models for the bone marrow niche and their potential for disease modeling and drug development.

## Key findings

- 3D models better replicate the bone marrow niche's structure and cell interactions compared to 2D cultures.
- Technologies like 3D bioprinting and organ-on-a-chip systems offer new ways to study hematopoiesis and drug resistance.
- Future directions include standardizing protocols and using human cells to improve model reproducibility and clinical relevance.

## Abstract

The bone marrow niche
is a specialized microenvironment sustaining
a hematopoietic stem cell (HSC) pool and regulating the production
of mature blood cells. Its exact composition and mechanisms remain
incompletely defined, mainly due to the lack of in vitro models that accurately reproduce its physiological three-dimensional
(3D) architecture and cellular crosstalk. Two-dimensional cultures
fail to sustain HSC quiescence and stemness, while advanced 3D systems
can reproduce key structural and mechanism cues of the niche. In this
review, we first describe physiological cellular, stromal, and matrix
components of the bone marrow niche, highlighting their coordinated
regulation of HSC maintenance, proliferation, and mobilization. We
then critically examine current approaches for 3D in vitro bone marrow models, including scaffold-based methods, decellularized
models, spheroid and organoid systems, 3D bioprinting applications,
and organ-on-chip technologies, discussing their advances, limitations,
and potential disease modeling in this field. Finally, we outline
how these technologies could deepen our understanding of hematopoiesis
mechanisms, clonal evolution, and niche-mediated drug resistance.
We also highlight the pros and cons of each methodology and future
directions toward standardized protocols, integrating tissue components,
and the use of human cells to enhance reproducibility and clinical
relevance. Advances like bone marrow-on-a-chip, computational models,
and patient-specific systems will help bridge the gap between in vitro and in vivo studies, enabling
drug testing, stem cell expansion, and gene editing strategies, including
chimeric antigen receptor expression. Bone marrow models have evolved
from simple 2D cultures to advanced 3D and organ-on-a-chip systems,
significantly improving our understanding of hematopoiesis and accelerating
new therapies.