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Review
. 2023 Jan 23;80(2):49.
doi: 10.1007/s00018-023-04696-w.

Hydrogel-based microenvironment engineering of haematopoietic stem cells

Meng Zhu #  1   2   3 , Qiwei Wang #  1   2   3 , Tianning Gu  2   3   4 , Yingli Han  1   2   3 , Xin Zeng  1   2   3 , Jinxin Li  1   2   3 , Jian Dong  1   2   3 , He Huang  5   6   7 , Pengxu Qian  8   9   10
Affiliations
Review

Hydrogel-based microenvironment engineering of haematopoietic stem cells

Meng Zhu et al. Cell Mol Life Sci. .

Abstract

Haematopoietic Stem cells (HSCs) have the potential for self-renewal and multilineage differentiation, and their behaviours are finely tuned by the microenvironment. HSC transplantation (HSCT) is widely used in the treatment of haematologic malignancies while limited by the quantity of available HSCs. With the development of tissue engineering, hydrogels have been deployed to mimic the HSC microenvironment in vitro. Engineered hydrogels influence HSC behaviour by regulating mechanical strength, extracellular matrix microstructure, cellular ligands and cytokines, cell-cell interaction, and oxygen concentration, which ultimately facilitate the acquisition of sufficient HSCs. Here, we review recent advances in the application of hydrogel-based microenvironment engineering of HSCs, and provide future perspectives on challenges in basic research and clinical practice.

Keywords: Bone marrow microenvironment; Engineered biomaterial; HSC expansion; HSCT; Haematopoietic stem cell (HSC); Stem cell niche.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1
Development and hierarchy of HSCs in mouse and human. a Embryonic sites of blood development in mice and humans. b Overview of the haematopoietic hierarchy. Created with BioRender.com
Fig. 2
Fig. 2
HSC niche during embryonic development in mice. The magnified images (right) show the embryonic HSC microenvironment in the AGM and FL. In the AGM, stromal cells and catecholamines released from the sympathetic nervous system regulate HSC differentiation. In the FL liver, HSCs undergo dramatic expansion before colonizing the BM. AGM aorta-gonad-mesonephros, FL foetal liver. Created with BioRender.com
Fig. 3
Fig. 3
Distinct niches in the adult bone marrow. The BM mainly includes the endosteal and perivascular niches. The endosteal niche, adjacent to the endosteum of the trabecular bone, contributes to maintaining quiescent HSCs, while the perivascular niche initiates HSC self-renewal and differentiation. Angpt1 angiopoietin-like 3, FL foetal liver, CAR cell cxcl12-abundant reticular cell, CXCL12 C-X-C motif chemokine ligand 12, HSC hematopoietic stem cell, LepR leptin receptor-expressing, NG2 neuron-glial 2, SCF stem cell factor, TGF-β transforming growth factor-β, TNF-α tumor necrosis factor-alpha, TPO thrombopoietin. Created with BioRender.com
Fig. 4
Fig. 4
The engineered HSC microenvironment known to regulate HSC states. To regulate HSC behaviour in vitro, the hydrogels mimic some aspects of the stem cell microenvironment, such as the mechanics, extracellular matrix microstructure, cell adhesive, cellular ligands and cytokines, cell–cell interactions, and oxygen concentration. Created with BioRender.com
Fig. 5
Fig. 5
Schematic of HSC transplantation combined with hydrogel platform. HSCs are obtained by stimulated mobilization or cord blood separation. Then, sufficient HSCs can be obtained by an engineered hydrogel platform mimicking the HSC microenvironment in vitro, and the HSCs are transfused into patients. Created with BioRender.com
See this image and copyright information in PMC

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