Engineering a Humanised Niche to Support Human Haematopoiesis in Mice: Novel Opportunities in Modelling Cancer
Open Access
- 6 August 2020
- Vol. 12 (8), 2205
- https://doi.org/10.3390/cancers12082205
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.Funding Information
- International Myeloma Foundation (Briand D Novis Junior Researcher Award)
- Instituto de Salud Carlos III (PI17/00701)
- CIBERONC (CB16/12/00489)
- Qatar National Research Fund (7-916-3-237)
This publication has 62 references indexed in Scilit:
- A Novel Mouse Model for Multiple Myeloma (MOPC315.BM) That Allows Noninvasive Spatiotemporal Detection of Osteolytic DiseasePLOS ONE, 2012
- Tug of war in the haematopoietic stem cell niche: do myeloma plasma cells compete for the HSC niche?Blood Cancer Journal, 2012
- Xenogeneic Graft-versus-Host-Disease in NOD-scid IL-2Rγnull Mice Display a T-Effector Memory PhenotypePLOS ONE, 2012
- Human extramedullary bone marrow in mice: a novel in vivo model of genetically controlled hematopoietic microenvironmentBlood, 2012
- The Immune Microenvironment of MyelomaCancer Microenvironment, 2011
- A unique three-dimensional SCID-polymeric scaffold (SCID-synth-hu) model for in vivo expansion of human primary multiple myeloma cellsLeukemia, 2011
- Humanized mouse models to study human diseasesCurrent Opinion in Endocrinology, Diabetes and Obesity, 2010
- Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myelomaBlood, 2009
- Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft-versus-host-like disease and the role of host major histocompatibility complexClinical and Experimental Immunology, 2009
- Cryopreservation of hematopoietic stem cellsAmerican Journal of Hematology, 2007