Generating hematopoietic cells from human pluripotent stem cells: approaches, progress and challenges

Haiqiong Zheng^#^{1

2

3

4}, Yijin Chen^#^{1

2

3

4}, Qian Luo^#^{1

2

3

4}, Jie Zhang^{1

2

3

4}, Mengmeng Huang^{1

2

3

4}, Yulin Xu^{1

2

3

4}, Dawei Huo^{1

2

3

4}, Wei Shan^{1

2

3

4}, Ruxiu Tie^{1

2

3

4}, Meng Zhang^{5

6

7

8}, Pengxu Qian^{9

10

11

12}, He Huang^{13

14

15

16}

Affiliations

¹ Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310012, China.
² Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, 311121, China.
³ Institute of Hematology, Zhejiang University, Hangzhou, 310012, China.
⁴ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, 310012, China.
⁵ Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310012, China. zhangm1990@zju.edu.cn.
⁶ Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, 311121, China. zhangm1990@zju.edu.cn.
⁷ Institute of Hematology, Zhejiang University, Hangzhou, 310012, China. zhangm1990@zju.edu.cn.
⁸ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, 310012, China. zhangm1990@zju.edu.cn.
⁹ Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, 311121, China. axu@zju.edu.cn.
¹⁰ Institute of Hematology, Zhejiang University, Hangzhou, 310012, China. axu@zju.edu.cn.
¹¹ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, 310012, China. axu@zju.edu.cn.
¹² Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. axu@zju.edu.cn.
¹³ Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310012, China. huanghe@zju.edu.cn.
¹⁴ Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, 311121, China. huanghe@zju.edu.cn.
¹⁵ Institute of Hematology, Zhejiang University, Hangzhou, 310012, China. huanghe@zju.edu.cn.
¹⁶ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, 310012, China. huanghe@zju.edu.cn.

^# Contributed equally.

PMID: 37656237
PMCID: PMC10474004
DOI: 10.1186/s13619-023-00175-6

Review

Generating hematopoietic cells from human pluripotent stem cells: approaches, progress and challenges

Haiqiong Zheng et al. Cell Regen. 2023.

. 2023 Sep 1;12(1):31.

doi: 10.1186/s13619-023-00175-6.

Authors

Affiliations

¹ Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310012, China.
² Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, 311121, China.
³ Institute of Hematology, Zhejiang University, Hangzhou, 310012, China.
⁴ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, 310012, China.
⁵ Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310012, China. zhangm1990@zju.edu.cn.
⁶ Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, 311121, China. zhangm1990@zju.edu.cn.
⁷ Institute of Hematology, Zhejiang University, Hangzhou, 310012, China. zhangm1990@zju.edu.cn.
⁸ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, 310012, China. zhangm1990@zju.edu.cn.
⁹ Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, 311121, China. axu@zju.edu.cn.
¹⁰ Institute of Hematology, Zhejiang University, Hangzhou, 310012, China. axu@zju.edu.cn.
¹¹ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, 310012, China. axu@zju.edu.cn.
¹² Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. axu@zju.edu.cn.
¹³ Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310012, China. huanghe@zju.edu.cn.
¹⁴ Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, 311121, China. huanghe@zju.edu.cn.
¹⁵ Institute of Hematology, Zhejiang University, Hangzhou, 310012, China. huanghe@zju.edu.cn.
¹⁶ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, 310012, China. huanghe@zju.edu.cn.

^# Contributed equally.

PMID: 37656237
PMCID: PMC10474004
DOI: 10.1186/s13619-023-00175-6

Erratum in

Correction: Generating hematopoietic cells from human pluripotent stem cells: approaches, progress and challenges.
Zheng H, Chen Y, Luo Q, Zhang J, Huang M, Xu Y, Huo D, Shan W, Tie R, Zhang M, Qian P, Huang H. Zheng H, et al. Cell Regen. 2023 Oct 9;12(1):32. doi: 10.1186/s13619-023-00177-4. Cell Regen. 2023. PMID: 37807020 Free PMC article. No abstract available.

Abstract

Human pluripotent stem cells (hPSCs) have been suggested as a potential source for the production of blood cells for clinical application. In two decades, almost all types of blood cells can be successfully generated from hPSCs through various differentiated strategies. Meanwhile, with a deeper understanding of hematopoiesis, higher efficiency of generating progenitors and precursors of blood cells from hPSCs is achieved. However, how to generate large-scale mature functional cells from hPSCs for clinical use is still difficult. In this review, we summarized recent approaches that generated both hematopoietic stem cells and mature lineage cells from hPSCs, and remarked their efficiency and mechanisms in producing mature functional cells. We also discussed the major challenges in hPSC-derived products of blood cells and provided some potential solutions. Our review summarized efficient, simple, and defined methodologies for developing good manufacturing practice standards for hPSC-derived blood cells, which will facilitate the translation of these products into the clinic.

Keywords: Blood cells; Hematopoietic differentiation; Hematopoietic stem cells; Human pluripotent stem cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Fig. 1**
Schematic representations of embryonic hematopoiesis in vivo. There are 3 waves of hematopoietic cell generation, including primitive, pro-definitive, and definitive HSC. Among them, the primitive hematopoietic cells, including erythrocytes, megakaryocytes and macrophages, emerge in the extraembryonic yolk sac blood islands; the pro-definitive wave of hematopoiesis occurs in the yolk sac and generates definitive erythro-myeloid progenitors (EMPs) and lymphoid-primed progenitors (LMPPs) in the yolk sac; the definitive HSCs arise in the intraembryonic aorta–gonad–mesonephros region (AGM) and migrate into the fetal liver for maturation, expansion and differentiation, then initiate mobilization to the bone marrow to supply life-long hematopoiesis

**Fig. 2**
Overview of current methods of inducing PSCs into blood cells in vitro and potential applications of PSCs-derived blood cells. Several differentiation methods have been developed to derive blood cells from PSCs in vitro at present: through the formation of EBs, co-culture with stromal cells and induced hematopoietic differentiation in a 3D-condition. The generated blood cells could be utilized in certain fields: (1) Drug discovery: developmental biology, host-microbe interactions, disease modeling and drug evaluation; (2) Medical treatment/therapy for clinical use, such as transplantation, personalized medicine and cell therapy

See this image and copyright information in PMC

References

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Generating hematopoietic cells from human pluripotent stem cells: approaches, progress and challenges

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Generating hematopoietic cells from human pluripotent stem cells: approaches, progress and challenges

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