In a new publication in Science Advances, Dai and colleagues showed how a BMP-2 osteo-organoid-loaded scaffold implanted into the muscle pocket close to a mouse femur can serve as a niche to promote the extensive recruitment of stem cells and mature immune cells.
iNSiGHT. Image Credit: Scintica Instrumentation Inc.
This in vivo osteo-organoid, consisting of a BMP-2-loaded gelatin scaffold, supported the generation of hematopoietic stem/progenitor cells, mesenchymal stem cells, lymphocytes, and myeloid through a three-stage process: fibroproliferation, osteochondral differentiation, and marrow generation.
In a radiation-damage assay, researchers successfully harvested and used osteochondral stage and marrow stage cells to treat hepatic injuries and rebuild the compromised immune system. These findings show the potential of the BMP-2 osteo-organoid as a sustainable source of high-quality stem and immune cells for cell therapies and regenerative medicine uses.
In this study, the researchers utilized the distinct capabilities of the iNSiGHT dual-energy X-ray absorptiometry (D(E)XA) system to quickly and noninvasively observe alterations in bone mineral density (BMD) and assess the time- and dose-dependence success of osteo-organoid formation following the implantation of the BMP-2-loaded gelatin scaffold (Figure 1).
Using the iNSiGHT D(E)XA system, the authors demonstrated that osteo-organoid development did not substantially change the overall body and femur BMD. They also used it to confirm a successful increase in BMD in the excised osteo-organoid, which allowed them to quickly determine the best and most economical dosage for osteo-organoid formation in subsequent experiments.
New INSIGHT software features enable BMD, fat, or lean mass assessment in specific regions of interest (ROIs) during post-processing, prompting additional evaluation of the dataset produced in this paper. This includes comparisons between the BMD of the osteo-organoid ROI acquired in vivo with the BMD, weight, and histopathological scoring of the excised osteo-organoid.
This data would aid in calibrating and further validating the iNSiGHT DEXA system and, by extension, clinical D(E)XA imaging as essential tools for noninvasive monitoring of osteo-organoid formation in vivo. This would further accelerate the clinical translation and assessment of this promising technique for harvesting stem cells and immune cells for medicinal purposes.
Figure 1. A) Dual-energy X-ray absorptiometry ((D(E)XA)) images of mice injected with varying dosages (10, 30, or 50 µg) of rhBMP-2 imaged 6 times up to 12 weeks. B, C, D) Bone mineral density (BMD) analysis for whole body, femur, and the osteo-organoid for the varying dosages and time points (week 1,2,3,4, and 12 post-implantations. Obvious bone generation was observed after only 2 weeks when comparing to the PBS control group, as confirmed by E) visual inspection and F) hematoxylin and eosin (H&E) staining of the excised tissue, highlighting granulated tissue (Gt), scaffolds (Sca), chondrocytes (Cc), muscle (Mu), bone marrow (BM), new bone (NB), and adipocytes (Ad). D(E)XA imaging confirmed a dosage of 30 µg as an adequate and cost-effective dose for the development of osteo-organoids for further experiments. Image Credit: Scintica Instrumentation Inc.
References and further reading:
Dai, K. et al. (2023). A BMP-2–triggered in vivo osteo-organoid for cell therapy. Science Advances, 9(1). https://doi.org/10.1126/sciadv.add1541.
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