Progress has been achieved in the art of accurately mimicking human tissues and disease in a mouse.

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.

Background: Various modalities to facilitate nerve regeneration have been described in the literature with limited success. We hypothesized that negative pressure applied to a sectioned peripheral nerve would enhance nerve regeneration by promoting angiogenesis and axonal lengthening. Methods: Wistar rats’ sciatic nerves were cut (creating ~7 mm nerve gap) and placed into a silicone T-tube, to which negative pressure was applied. The rats were divided into 4 groups: control (no pressure), group A (low pressure: 10 mm Hg), group B (medium pressure: 20/30 mm Hg) and group C (high pressure: 50/70 mm Hg). The nerve segments were retrieved after 7 days for gross and histological analysis. Results: In total, 22 rats completed the study. The control group showed insignificant nerve growth, whereas the 3 negative pressure groups showed nerve growth and nerve gap reduction. The true nerve growth was highest in group A (median: 3.54 mm) compared to group B, C, and control (medians: 1.19 mm, 1.3 mm, and 0.35 mm); however, only group A was found to be significantly different to the control group (**P < 0.01). Similarly, angiogenesis was observed to be significantly greater in group A (**P < 0.01) in comparison to the control. Conclusions: Negative pressure stimulated nerve lengthening and angiogenesis within an in vivo rat model. Low negative pressure (10 mm Hg) provided superior results over the higher negative pressure groups and the control, favoring axonal growth. Further studies are required with greater number of rats and longer recovery time to assess the functional outcome.