Generation of iPSC-Derived Mesenchymal Stromal Cells (iMSCs) for Ex Vivo Acute Myeloid Leukemia (AML) Niche Models

The development of AML depends on cell-extrinsic changes from the bone marrow (BM) microenvironment modulating leukeamia initiation and progression. However, studying the communication between AML cells and niche components requires reliable and modifiable niche components. Here, we describe the controlled differentiation of induced pluripotent stem cells (iPSC) into iMSC lines through mesodermal and ectodermal induction pathways. Five distinct iMSC lineages were generated and thoroughly characterised throughout their production process. Their stemness and stability were assessed using tri-lineage differentiation and colony formation assays revealing differences in their pre-osteoblastic or pre-adiposite potential. Notably, these iMSC lineages exhibit varying capacities to support the maintenance of immature primary AML cells in iMSCs/AML co-culture systems. Together, we describe the generation of distinct iMSC lines that mimic key AML supporting components within the BM niche. These iMSC will serve as a tool for the development of BM-like platforms enabling the investigation and controlled manipulation of the crosstalk between AML cells and the stromal microenvironment ex vivo.

Publikationsverlauf

Artikel online veröffentlicht:
09. Mai 2025