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Article

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

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Regenerative Medicine Institute, School of Medicine, National University of Ireland Galway, H91W2TY Galway, Ireland
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Department of Chemistry, University of South Florida, Tampa, FL 33620, USA
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Martin Ryan Institute, School of Natural Sciences, National University of Ireland Galway, University Road, H91TK33 Galway, Ireland
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Genomics and Screening Core, National University of Ireland Galway, H91W2TY Galway, Ireland
*
Authors to whom correspondence should be addressed.
Academic Editor: Marc Diederich
Mar. Drugs 2021, 19(7), 390; https://doi.org/10.3390/md19070390
Received: 2 June 2021 / Revised: 5 July 2021 / Accepted: 9 July 2021 / Published: 13 July 2021
(This article belongs to the Special Issue Marine-Inspired Regenerative Strategies for Chronic Diseases)
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. View Full-Text
Keywords: High-throughput screening; hMSC; anti-inflammatory; regenerative medicine; marine fungi; natural products; osteoarthritis; osteoporosis High-throughput screening; hMSC; anti-inflammatory; regenerative medicine; marine fungi; natural products; osteoarthritis; osteoporosis
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MDPI and ACS Style

Marchese, P.; Young, R.; O’Connell, E.; Afoullouss, S.; Baker, B.J.; Allcock, A.L.; Barry, F.; Murphy, J.M. Deep-Sea Coral Garden Invertebrates and Their Associated Fungi Are Genetic Resources for Chronic Disease Drug Discovery. Mar. Drugs 2021, 19, 390. https://doi.org/10.3390/md19070390

AMA Style

Marchese P, Young R, O’Connell E, Afoullouss S, Baker BJ, Allcock AL, Barry F, Murphy JM. Deep-Sea Coral Garden Invertebrates and Their Associated Fungi Are Genetic Resources for Chronic Disease Drug Discovery. Marine Drugs. 2021; 19(7):390. https://doi.org/10.3390/md19070390

Chicago/Turabian Style

Marchese, Pietro, Ryan Young, Enda O’Connell, Sam Afoullouss, Bill J. Baker, A. L. Allcock, Frank Barry, and J. M. Murphy. 2021. "Deep-Sea Coral Garden Invertebrates and Their Associated Fungi Are Genetic Resources for Chronic Disease Drug Discovery" Marine Drugs 19, no. 7: 390. https://doi.org/10.3390/md19070390

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