Engineering a humanised niche to support human haematopoiesis in mice: novel opportunities in modelling cancer

Autores: Sánchez-Herrero, A.; Calvo, I. A. ; Flandes Iparraguirre, María; Landgraf, M.; Lahr, C. A.; Shafiee, A.; Granero Molto, Froilan; Sáez Ochoa, Borja; Mazo Vega, Manuel María; Paiva, Bruno; Juan Pardo, María Elena; Nicol, A.; Prosper Cardoso, Felipe; Bray, L. J.; McGovern, J. A.
Título de la revista: CANCERS
ISSN: 2072-6694
Volumen: 12
Número: 8
Páginas: 2205
Fecha de publicación: 2020
Despite the bone marrow microenvironment being widely recognised as a key player in cancer research, the current animal models that represent a human haematopoietic system lack the contribution of the humanised marrow microenvironment. Here we describe a murine model that relies on the combination of an orthotopic humanised tissue-engineered bone construct (ohTEBC) with patient-specific bone marrow (BM) cells to create a humanised bone marrow (hBM) niche capable of supporting the engraftment of human haematopoietic cells. Results showed that this model supports the engraftment of human CD34+ cells from a healthy BM with human haematopoietic cells migrating into the mouse BM, human BM compartment, spleen and peripheral blood. We compared these results with the engraftment capacity of human CD34+ cells obtained from patients with multiple myeloma (MM). We demonstrated that CD34+ cells derived from a diseased BM had a reduced engraftment potential compared to healthy patients and that a higher cell dose is required to achieve engraftment of human haematopoietic cells in peripheral blood. Finally, we observed that hematopoietic cells obtained from the mobilised peripheral blood of patients yields a higher number of CD34+, overcoming this problem. In conclusion, this humanised mouse model has potential as a unique and patient-specific pre-clinical platform for the study of tumour-microenvironment interactions, including human bone and haematopoietic cells, and could, in the future, serve as a drug testing platform.