Using human iPSC-derived bone marrow organoids to model human bone marrow diseases ex vivo

NU 2024-129

INVENTORS

Peng Ji*

Ermin Li

Kehan Ren

SHORT DESCRIPTION

Methods and factors for engrafting a bone marrow organoid with CD34+ hematopoietic stem and progenitor cells

BACKGROUND

Translational research for hematological diseases often relies on engrafting hematopoietic stem and progenitor cells (HSPCs) into immunodeficient mouse models. However, differences between human and mouse bone marrow microenvironments can result in findings that poorly translate to clinical settings. Organoids offer a compelling alternative, providing greater physiological relevance and ease of ex vivo manipulation. Currently, fully developed bone marrow organoids that accurately recapitulate human diseases or support autonomous hematopoiesis remain limited. Organoids capable of engrafting challenging HSPCs, such as those derived from patients with myelodysplastic syndrome (MDS) patients, have yet to be explored.

ABSTRACT

Northwestern researchers have developed a method for generating human induced pluripotent stem cell (iPSCs)-derived bone marrow organoids that closely mimic actual human bone marrow microenvironment and support autonomous hematopoiesis. These organoids efficiently support engraftment, self-renewal, and multilineage differentiation of HSPCs, including those from patients with MDS. Importantly, the organoids preserve the genetic and disease-specific profiles of these cells, accurately recapitulating disease pathophysiology. The organoid provides a powerful tool for studying hematopoiesis, modeling disease processes, and evaluating therapeutic treatments in a controlled ex vivo setting.

APPLICATIONS

• Ex vivo modeling for hematopoietic diseases, including myelodysplastic syndromes (MDS)
• Therapeutic development (target validation, drug screening, toxicity assessment)
• Relevant for applications in personalized medicine

ADVANTAGES

• Enables the efficient engraftment of challenging HSPCs from patients with MDS
• Closely mimics the complex cellular composition of the native bone marrow
• Supports the growth and multilineage differentiation of engrafted HSPCs
• Capable of autonomous hematopoiesis, a process where the bone marrow organoid can independently produce different blood cells without exogenously provided feeder cells or growth factors

PUBLICATIONS

Ren, K.; Li, E.; Aydemir, I.; Liu, Y.; Han, X.; Bi, H.; Wang, P.; Tao, K.; Ji, A.; Chen, Y.-H.; Yang, J.; Sukhanova, M.; Ji, P. Development of iPSC-Derived Human Bone Marrow Organoid for Autonomous Hematopoiesis and Patient-Derived HSPC Engraftment. Blood Adv. 2025, 9 (1), 54–65. https://doi.org/10.1182/bloodadvances.2024013361.

IP STATUS

US patent pending.