Deep-Sea Coral Garden Invertebrates and Their Associated Fungi Are Genetic Resources for Chronic Disease Drug Discovery

Chronic diseases characterized by bone and cartilage loss are associated with a reduced ability of progenitor cells to regenerate new tissues in an inflammatory environment. A promising strategy to treat such diseases is based on tissue repair mediated by human mesenchymal stem cells (hMSCs), but therapeutic outcomes are hindered by the absence of small molecules to efficiently modulate cell behaviour. Here, we applied a high-throughput drug screening technology to bioprospect a large library of extracts from Irish deep-sea organisms to induce hMSC differentiation toward musculoskeletal lineages and reduce inflammation of activated macrophages. The library included extracts from deep-sea corals, sponges and filamentous fungi representing a novel source of compounds for the targeted bioactivity. A validated hit rate of 3.4% was recorded from the invertebrate library, with cold water sea pens (octocoral order Pennatulacea), such as Kophobelemnon sp. and Anthoptilum sp., showing the most promising results in influencing stem cell differentiation toward osteogenic and chondrogenic lineages. Extracts obtained from deep-sea fungi showed no effects on stem cell differentiation, but a 6.8% hit rate in reducing the inflammation of activated macrophages. Our results demonstrate the potential of deep-sea organisms to synthetize pro-differentiation and immunomodulatory compounds that may represent potential drug development candidates to treat chronic musculoskeletal diseases.

Automated summary

High-throughput drug screening of extracts from Irish deep-sea organisms revealed a validated hit rate of 3.4% in the invertebrate library, with cold water sea pens showing promising results in influencing stem cell differentiation. Extracts from deep-sea fungi had no effects on stem cell differentiation, but showed a 6.8% hit rate in reducing inflammation of activated macrophages. These results demonstrate the potential of deep-sea organisms to produce compounds for drug development in treating chronic musculoskeletal diseases.