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

Authors
  • Sanchez-Herrero, Alvaro
  • Calvo, Isabel A.
  • Flandes-Iparraguirre, Maria
  • Landgraf, Marietta
  • Lahr, Christoph A.
  • Shafiee, Abbas
  • Granero-Molto, Froilán
  • Saez, Borja
  • Mazo, Manuel M.
  • Paiva, Bruno
  • Pardo, Elena de Juan
  • Nicol, Andrew
  • Prosper, Felipe
  • Bray, Laura J.
  • McGovern, Jacqui A.
Publication Date
Aug 01, 2020
Source
Queensland University of Technology ePrints Archive
Keywords
License
Unknown

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.

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