Engineering a Humanised Niche to Support Human Haematopoiesis in Mice: Novel Opportunities in Modelling Cancer.
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.
['Sanchez-Herrero|Alvaro|A|0000-0002-6346-2822', 'Calvo|Isabel A|IA|0000-0001-6619-4571', 'Flandes-Iparraguirre|Maria|M|', 'Landgraf|Marietta|M|', 'Lahr|Christoph A|CA|', 'Shafiee|Abbas|A|0000-0002-8885-9025', 'Granero-Molto|Froilán|F|0000-0003-4817-5232', 'Saez|Borja|B|0000-0001-7908-7089', 'Mazo|Manuel M|MM|0000-0002-6250-5579', 'Paiva|Bruno|B|', 'de Juan Pardo|Elena|E|0000-0001-9005-7497', 'Nicol|Andrew|A|', 'Prosper|Felipe|F|0000-0001-6115-8790', 'Bray|Laura J|LJ|0000-0002-1174-0018', 'McGovern|Jacqui A|JA|0000-0002-4993-6745']
bone marrow multiple myeloma humanised mouse model CD34+ haematopoietic stem cell tissue engineering tumour microenvironment