# Development of an Organoid-Derived Exosome Product for the Treatment of Osteoarthritis > **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2024 · $423,500 ## Abstract Summary/Abstract Osteoarthritis (OA) is a chronic debilitating joint disease, affecting over 32 million people in the USA with an economic impact of $550 billion/year. OA is characterized by degeneration of articular cartilage, typically affecting the back, hands, knees, and hips. A significant correlation between inflammation and disease severity has been observed in human and animal models of OA. Increased inflammation in the synovial fluid has also been shown to inhibit chondrocyte proliferation limiting cartilage repair and promoting OA disease progression. No therapy is available to slow the progression of OA and current treatments only attempt to relieve the symptoms. New therapeutics that promote regulation of inflammation have the potential to alleviate the OA pathology and arrest the disease progression. The impact of fetal development on the immune system varies depending on the stage of embryo development with a delicate balance between immune tolerance and protective immunity. Several extrinsic and intrinsic factors through epigenetic and transcriptional programs skew the adaptive immune response towards increased expression of immunosuppressive signaling intermediates including Helios that favors the expansion of Tregs. Exosomes play a critical role in cross talk between different biological systems. In this study we will leverage the immunoregulatory mechanisms in play during the fetal development to treat OA by identifying the stage of muti-tissue organoid (MTO)-development that yields exosomes with anti-inflammatory and chondrocyte proliferation potential in in vitro studies using human PBMCs to facilitate clinical translation. We will analyze the epigenetic and transcriptomic reprograming induced by the MTO-derived exosomes that promote expansion of iTregs that can play a critical role in the regulation of inflammation in OA. We will also test the MTO- derived exosomes to alleviate OA symptoms in a rat model of OA. The studies will also identify protein and miRNA in the MTO-derived exosomal cargo that correlates with anti-inflammatory and chondrocyte proliferation potential that can be developed into potency assays for use in future clinical trials for evaluation of the MTO-derived exosomes. ## Key facts - **NIH application ID:** 10888061 - **Project number:** 1R21AG083324-01A1 - **Recipient organization:** UNIVERSITY OF MINNESOTA - **Principal Investigator:** Timothy D O'Brien - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $423,500 - **Award type:** 1 - **Project period:** 2024-08-15 → 2026-07-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10888061 ## Citation > US National Institutes of Health, RePORTER application 10888061, Development of an Organoid-Derived Exosome Product for the Treatment of Osteoarthritis (1R21AG083324-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10888061. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*