Engineering a Humanised Niche to Support Human Haematopoiesis in Mice: Novel Opportunities in Modelling Cancer

Alvaro Sanchez-Herrero, Isabel A Calvo, Maria Flandes-Iparraguirre, Marietta Landgraf, Christoph A Lahr, Abbas Shafiee, Froilán Granero-Molto, Borja Saez, Manuel M Mazo, Bruno Paiva, Elena de Juan Pardo, Andrew Nicol, Felipe Prosper, Laura J Bray, Jacqui A McGovern

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Number of pages23
JournalCancers
Volume12
Issue number8
DOIs
Publication statusPublished - Aug 2020

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