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Using multi-organ culture systems to study Parkinson’s disease

Molecular Psychiatry volume 26, pages 725–735 (2021)Cite this article

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Abstract

In recent years, it has been revealed that Parkinson’s disease pathology may begin to manifest in the gastrointestinal track at a much earlier time point than in the brain. This paradigm shift has been suggested following evidence in humans that has been reproduced in animal models. Since rodent models cannot recapitulate many of the human disease features, human induced pluripotent stem cells derived from Parkinson’s patients have been used to generate brain organoids, greatly contributing to our understanding of the disease pathophysiology. To understand the multifaced aspects of Parkinson’s disease, it may be desirable to expand the complexity of these models, to include different brain regions, vasculature, immune cells as well as additional diverse organ-specific organoids such as gut and intestine. Furthermore, the contribution of gut microbiota to disease progression cannot be underestimated. Recent biotechnological advances propose that such combinations may be feasible. Here we discuss how this need can be met and propose that additional brain diseases can benefit from this approach.

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Fig. 1: Schematic presentation of PD in human patients and mouse models.
Fig. 2: Present and future in vitro models for PD.

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Acknowledgements

OR is an incumbent of the Bernstein-Mason Chair of Neurochemistry, Head of the M. Judith Ruth Institute for Preclinical Brain Research, TS is incumbent of the Leir Research Fellow Chair in Autism Spectrum Disorder Research. We thank Dr. Samara Brown for editing the first version of this manuscript. Our research is supported by The Jeanne and Joseph Nissim Center for Life Sciences Research at the Weizmann Institute of Science, the Helen and Martin Kimmel Institute for Stem Cell Research, the Nella and Leon Benoziyo Center for Neurological Diseases, the David and Fela Shapell Family Center for Genetic Disorders Research, the Brenden-Mann Women’s Innovation Impact Fund, the Richard F. Goodman Yale/Weizmann Exchange Program, The Irving B. Harris Fund for New Directions in Brain Research, The Irving Bieber, M.D. and Toby Bieber, M.D. Memorial Research Fund, The Leff Family, Barbara & Roberto Kaminitz, Sergio & Sônia Lozinsky, Debbie Koren, Jack and Lenore Lowenthal, and the Dears Foundation. The research has been supported by the Israel Science Foundation (Grant No. 347/15), the Legacy Heritage Biomedical Program of the Israel Science Foundation (Grant No. 2041/16), Israel Science Foundation (ISF)—National Natural Science Foundation of China (NSFC) (grant No. 2449/16), grant No. 2397/18 from the Canadian Institutes of Health Research (CIHR), the International Development Research Centre (IDRC), the Israel Science Foundation (ISF) and the Azrieli Foundation, a grant from the Ministry of Science & Technology, Israel & The Ministry of Science and Technology of the People’s Republic of China, German-Israeli Foundation (GIF; Grant no. I-1476-203.13/2018), and United States-Israel Binational Science Foundation (BSF; Grant No. 2017006).

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  1. Department of Molecular Genetics, Weizmann Institute of Science, 234 Herzl str., 7610001, Rehovot, Israel

    Orly Reiner & Tamar Sapir

  2. Tata Institute of Fundamental Research, Mumbai, India

    Arpan Parichha

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  1. Orly Reiner
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  2. Tamar Sapir
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Correspondence to Orly Reiner.

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Reiner, O., Sapir, T. & Parichha, A. Using multi-organ culture systems to study Parkinson’s disease. Mol Psychiatry 26, 725–735 (2021). https://doi.org/10.1038/s41380-020-00936-8

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