4.6 Review

Using Pluripotent Stem Cells to Understand Normal and Leukemic Hematopoietic Development

Journal

STEM CELLS TRANSLATIONAL MEDICINE
Volume 11, Issue 11, Pages 1123-1134

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/stcltm/szac071

Keywords

pluripotent stem cells; adult haematopoietic stem cells; embryo; embryonic stem cells (ESCs); hematologic malignancies

Funding

  1. Agencia Estatal de Investigacion (AEI) [PID2019-104695RB-I00, PDC2021-120817-I00]
  2. Department of Health of the Government of Catalonia [SLT011/18/00006, SLT011/18/00007]
  3. Spanish Ministry of Economy, Industry, and Competitiveness (MINECO) [PID2020-15591RB-100]
  4. La Marato de TV3 [202001-32]
  5. CERCA Programme/Generalitat de Catalunya
  6. AGAUR, Generalitat de Cataluna [2021 FI_B2 00188]

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Researchers have been studying embryonic stem cells for several decades, aiming to use them in regenerative medicine. The hematopoietic field has been a pioneer in utilizing stem cells for blood cell development and clinical applications. However, generating authentic hematopoietic stem cells has proven to be challenging. While progress has been made in understanding the origin of these cells during embryonic development, reproducing this process in the lab is still not possible. Nevertheless, knowledge gained from studying embryonic development is being applied to pluripotent stem cells derived from mice and humans. Additionally, studies have shown that hematopoietic cells derived from embryonic stem cells can recapitulate some leukemic transformation processes, making them valuable for modeling prenatal leukemia development and other leukemia-predisposing syndromes.
Several decades have passed since the generation of the first embryonic stem cell (ESC) lines both in mice and in humans. Since then, stem cell biologists have tried to understand their potential biological and clinical uses for their implementation in regenerative medicine. The hematopoietic field was a pioneer in establishing the potential use for the development of blood cell products and clinical applications; however, early expectations have been truncated by the difficulty in generating bonafide hematopoietic stem cells (HSCs). Despite some progress in understanding the origin of HSCs during embryonic development, the reproduction of this process in vitro is still not possible, but the knowledge acquired in the embryo is slowly being implemented for mouse and human pluripotent stem cells (PSCs). In contrast, ESC-derived hematopoietic cells may recapitulate some leukemic transformation processes when exposed to oncogenic drivers. This would be especially useful to model prenatal leukemia development or other leukemia-predisposing syndromes, which are difficult to study. In this review, we will review the state of the art of the use of PSCs as a model for hematopoietic and leukemia development.

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