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Stem Cell Niche: iPSC-Based Assembloids for Modeling Human Hematopoiesis.

Madeline J Caduc1,2,3,4, Marcelo A S de Toledo5,6, Steffen Koschmieder7,8

  • 1Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain. mcaduc-ibis@us.es.

Methods in Molecular Biology (Clifton, N.J.)
|June 3, 2025
PubMed
Summary

Researchers developed patient-specific 3D bone marrow (BM) assembloids to study blood formation. This innovative platform models healthy and diseased BM niches, aiding research into hematopoietic regulation and myeloproliferative neoplasms.

Keywords:
AssembloidsBone marrow nicheHematopoiesisMicroenvironmentPatient-derived induced pluripotent stem cells

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Area of Science:

  • Hematology
  • Stem Cell Biology
  • Biotechnology

Background:

  • The bone marrow (BM) niche is critical for regulating hematopoiesis (blood cell formation) in health and disease.
  • Understanding the complex cellular interactions within the BM niche is essential for developing new treatments.

Purpose of the Study:

  • To present a protocol for generating patient-specific 3D BM-mimicking assembloids.
  • To provide an in vitro platform for dissecting mechanisms of hematopoietic regulation and BM niche remodeling.
  • To model both physiological and neoplastic BM niches for preclinical research.

Main Methods:

  • Stepwise differentiation of induced pluripotent stem cells (iPSCs) into hematopoietic and endothelial lineages.
  • Isolation of human primary mesenchymal stromal cells (MSCs) from femoral heads.
  • Assembly of 3D BM-mimicking assembloids and single-cell RNA sequencing.

Main Results:

  • Identification of key myeloid populations, endothelial cells, and MSC clusters within the assembloids.
  • Demonstration that assembloids with the JAK2V617F mutation recapitulate myeloproliferative neoplasms.
  • Validation of the platform for studying stem cell fate and niche maintenance.

Conclusions:

  • Patient-specific 3D BM assembloids offer precise control over cellular composition and genetic background.
  • This platform facilitates mechanistic studies in human hematopoiesis and models neoplastic BM niches.
  • The approach supports preclinical research and drug development, potentially reducing animal model use.