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COMMENTARY
Bone marrow organoids: Decoding the

three-dimensional code of hematopoietic niches

Liangyu Guo , Yifan Xia , Panpan Pan* , and Jingdi Chen*
Department of Marine Pharmacy, Marine College, Shandong University, Weihai, Shandong, China
*Corresponding authors: Panpan Pan (pppan@sdu.edu.cn); Jingdi Chen (jdchen@sdu.edu.cn)

Citation: Guo L, Xia Y, Pan P, Chen J. Abstract
Bone marrow organoids: Decoding
the three-dimensional code of The bone marrow serves not only as a “factory” for hematopoiesis but also as a
hematopoietic niches. Organoid Res.
2025;1(2):025110011. dynamic ecological “repository” regulating immune responses, metabolic processes,
doi: 10.36922/OR025110011 and disease progression. Its complexity stems from the three-dimensional interplay
Received: March 16, 2025 of vascular networks, mesenchymal stromal cells, hematopoietic stem cells, and
immune cells - a spatial dynamism poorly captured by traditional models. Recently,
Revised: April 22, 2025
the first functional human bone marrow organoids were constructed in vitro through
Accepted: April 28, 2025 multilineage differentiation and self-organization of induced pluripotent stem cells.
Published online: May 15, 2025 This model accurately captures the key functional and structural characteristics of
the human bone marrow hematopoietic niche, marking a significant milestone in
Copyright: © 2025 Author(s).
This is an Open-Access article advancing research on hematopoietic development and bone marrow diseases.
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution, and Keywords: Bone marrow organoids; Human induced pluripotent stem cells;
reproduction in any medium, which Hematopoietic microenvironment
provided that the original work is
properly cited.
Publisher’s Note: AccScience
Publishing remains neutral with regard
to jurisdictional claims in published
maps and institutional affiliations.

1. Introduction the molecular logic of definitive hematopoiesis during
embryogenesis.
Conventional bone marrow models often rely on single
exogenous cytokines (e.g., granulocyte colony-stimulating To promote organoid self-assembly, researchers
factor) to induce hematopoiesis. In a previous study, embedded differentiating embryoid bodies in a collagen I/
1,2
researchers adopted a multi-signal strategy to recapitulate Matrigel matrix on Day 4 to guide cellular self-organization
developmental dynamics. Specifically, they induced through biomechanical microenvironments. Three-
3
pluripotent stem cells through stepwise differentiation dimensional imaging revealed that vascular (CD31 )
+
within 3 weeks to generate complex organoids composed networks were enveloped by perivascular platelet-derived
of hematopoietic cells, mesenchymal cells, and endothelial growth factor beta, forming functional lumens. Nestin
cells. Following embryoid body formation (Day 3), stromal cells extended protrusions that closely neighbored
mesoderm was induced using the Wnt agonist CHIR99021, hematopoietic cells (CD45 ), recapitulating the structural
+
bone morphogenetic protein 4, and vascular endothelial features of the in vivo perivascular niche. This “bottom-up”
growth factor (Day 0). Subsequently, mesodermal assembly approach overcomes the spatial limitations of
4,5
patterning and hemogenic endothelial induction were traditional co-culture systems. 6,7
achieved using the activin/nodal pathway inhibitor
SB431542, basic fibroblast growth factor, stem cell factor, Single-cell RNA sequencing (scRNA-seq) unveiled the
and vascular endothelial growth factor (Day 2) (Figure 1A). molecular diversity of bone marrow organoids (BMOs),
This endogenous signal-driven approach not only avoids including hematopoietic populations (encompassing
interference from exogenous factors but also mirrors lymphoid progenitors [interleukin-7 receptor ],
+

Volume 1 Issue 2 (2025) 1 doi: 10.36922/OR025110011