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

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.