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Ex Vivo Culture Models of Hidradenitis Suppurativa for Defining Molecular Pathogenesis and Treatment Efficacy of Novel Drugs

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Abstract—

Hidradenitis suppurativa (HS) is a complex and debilitating inflammatory skin disease for which no effective treatment is available currently. This is partly because of the lack of adequate human or animal models for defining the pathobiology of the disease. Here, we describe the development of air–liquid (A-L) interface, liquid-submersion (L-S), and bioreactor (Bio) ex vivo skin culture models. All three ex vivo platforms were effective for culturing skin samples for up to 14 days. Tissue architecture and integrity remained intact for at least 3 days for healthy skin and 14 days for HS skin. Up to day 3, no significant differences were observed in % early apoptotic cells among all three platforms. However, late apoptotic/necrotic cell death was increased in HS skin at day 3 in A-L and Bio culture. These cultures efficiently support the growth of various cells populations, including keratinocytes and immune cells. Profiling inflammatory gene signatures in HS skin from these ex vivo cultures showed dynamic changes in expression at day 3 and day 14. All three culture platforms were necessary to represent the inflammatory gene status of HS skin at day 0, suggesting that not all gene clusters were identically altered in each culture method. Similarly, cytokine/chemokine profiling of the supernatants from vehicle- and drug-treated ex vivo HS cultures again showed a better prediction of drug efficacy against HS. Overall, development of these three culture systems collectively provides a powerful tool to uncover the pathobiology of HS progression and screen various drugs against HS.

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Data generated/analyzed during this study are included in this published article (and its supplementary information files).

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Funding

NIH grant RO1 ES026219 and NCI grant 5P01CA210946 and by intramural UAB funds to M.A.

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Authors and Affiliations

  1. Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Kayla F. Goliwas & Jessy S. Deshane

  2. UAB Research Center of Excellence in Arsenicals, Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Mahendra P. Kashyap, Jasim Khan, Rajesh Sinha, Zhiping Weng, Lin Jin, Venkatram Atigadda, Madison B. Lee, Craig A. Elmets, Chander Raman & Mohammad Athar

  3. Department of Dermatology, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Allen S. W. Oak

  4. UAB Medical Student for Scholarly Activity, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Madison B. Lee

  5. Department of Biology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    M. Shahid Mukhtar

Authors
  1. Kayla F. Goliwas
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  2. Mahendra P. Kashyap
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  4. Rajesh Sinha
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  7. Lin Jin
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  13. Jessy S. Deshane
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  14. Mohammad Athar
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Contributions

Conceived and designed the experiments: J.S.D., C.R., M.S.M., M.A. Performed the experiments: K.F.G., M.P.K., J.K., R.S., Z.W., A.O., L.J., V.A., M.B.L. Analyzed the data: K.F.G., M.P.K., J.K., R.S., Z.W., A.O., L.J., V.A., M.B.L., C.A.E., M.S.M., C.R., J.S.D., M.A. Contributed reagents/materials/analysis tools: C.A.E., M.S.M., C.R., J.S.D., M.A. Wrote the paper: K.F.G., M.P.K., J.S.D., and M.A.

Corresponding authors

Correspondence to Jessy S. Deshane or Mohammad Athar.

Ethics declarations

Ethical Approval and Consent to Participate

The institutional Review Board of the University of Alabama at Birmingham approved the protocol (IRB-300005214) for obtaining surgically removed discarded skin tissues from breast/tummy reduction from otherwise healthy individuals and HS patients.

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All authors agree to submit this manuscript.

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The authors declare no competing interests.

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Goliwas, K., Kashyap, M.P., Khan, J. et al. Ex Vivo Culture Models of Hidradenitis Suppurativa for Defining Molecular Pathogenesis and Treatment Efficacy of Novel Drugs. Inflammation 45, 1388–1401 (2022). https://doi.org/10.1007/s10753-022-01629-w

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  • DOI: https://doi.org/10.1007/s10753-022-01629-w

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