Engineering human mini-bones for the standardized modeling of healthy hematopoiesis, leukemia, and solid tumor metastasis

• DOI: 10.1126/scitranslmed.abm6391
• Publication Date: 2022-10-12T17:58:15Z
• Authors: Ani Grigoryan; Dimitra Zacharaki; Alexander Balhuizen; Christophe RM Côme; Alejandro Garcia ...; David Hidalgo Gil; Anne-Katrine Frank; Kristina Aaltonen; Adriana Mañas; Javanshir Esfandyari; Pontus Kjellman; Emelie Englund; Carmen Rodriguez; Wondossen Sime; Ramin Massoumi; Nasim Kalantari; Sujeethkumar Prit...; Yuan Li; Steven J Dupard; Hanna Isaksson; Chris D Madsen; Bo T Porse; Daniel Bexell; Paul E Bourgine
• Keywords: Disease Models, Animal; Leukemia, Myeloid, Acute; Mice; 0303 health sciences; 03 medical and health sciences; Tumor Microenvironment; Animals; Humans; Reproducibility of Results; Stem Cell Niche; Bone and Bones; Hematopoiesis

The bone marrow microenvironment provides indispensable factors to sustain blood production throughout life. It is also a hotspot for the progression of hematologic disorders and most frequent site solid tumor metastasis. Preclinical research relies on xenograft mouse models, but these models preclude human-specific functional interactions stem cells with their microenvironment. Instead, human mesenchymal can be exploited in vivo engineering humanized niches, which confer robust engraftment healthy malignant samples. However, are associated major reproducibility issues tissue formation. Here, we report fast standardized generation mini-bones by custom-designed cell line. These resulting ossicles (hOss) consist fully mature structures hosting niche retained properties. As compared bones, demonstrate superior cord hematopoietic primary acute myeloid leukemia samples validate hOss as metastatic breast cancer cells. We further neuroblastoma patient-derived model, recapitulating clinically described osteolytic lesions. Collectively, our constitute powerful preclinical platform model bone-developing tumors using materials.