Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Hot Topics
  • Published:

Postmortem-derived iPSC models in substance use disorders research

Neuropsychopharmacology volume 49, pages 349–350 (2024)Cite this article

Subjects

Patient-derived induced pluripotent stem cell (iPSC) models have accelerated discovery in the biomedical sciences, with high potential to model human physiology and disease. The use of these models in substance use disorders (SUD) has been limited. Studies using iPSC-derived dopaminergic neurons have explored the effects of genetic polymorphisms in opioid-dependent patients [1, 2], and iPSC-derived models of non-neuronal drug exposure, including endothelial cells and cardiomyocytes, have been established. While these studies shed light on effects of drugs in SUD, how well the models recapitulate the actual drug-induced brain alterations, genomic landscape and cell function remains to be determined.

More complex in vitro systems are currently being engineered to model tissue- and systems-level responses to drugs. Recent studies using organoid models of opioid use disorder show differential transcriptomic signatures between oxycodone and buprenorphine [4]. Additionally, multi-organ cell culture systems including organs-on-a-chip shed light on complex multi-system interactions between brain and other organs. These systems can be employed in postmortem-derived iPSC models for isogenic validation of response to drugs, with potential for replicable, high-throughput assays exploring drug dose response and timing, to replicate human-specific signatures of acute or chronic drug exposures.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Using postmortem-derived iPSC lines to model drug exposure.

References

  1. Sheng Y, Filichia E, Shick E, Preston KL, Phillips KA, Cooperman L, et al. Using iPSC‐derived human DA neurons from opioid‐dependent subjects to study dopamine dynamics. Brain Behav. 2016;6:491.

    Article  Google Scholar 

  2. Halikere A, Popova D, Scarnati MS, Hamod A, Swerdel MR, Moore JC, et al. Addiction associated N40D mu-opioid receptor variant modulates synaptic function in human neurons. Mol Psychiatry. 2019;25:1406–19.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Mendez EF, Grimm SL, Stertz L, Gorski D, Movva SV, Najera K, et al. A human stem cell-derived neuronal model of morphine exposure reflects brain dysregulation in opioid use disorder: Transcriptomic and epigenetic characterization of postmortem-derived iPSC neurons. Front Psychiatry. 2023;14:1070556.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ho, MF, Zhang, C, Moon, I, Zhu, X, Coombes, BJ, Biernacka, J, et al. Single cell transcriptomics reveals distinct transcriptional responses to oxycodone and buprenorphine by iPSC-derived brain organoids from patients with opioid use disorder. Mol Psychiatry. 2022. https://doi.org/10.1038/s41380-022-01837-8. Epub ahead of print.

  5. Zuk P, Stertz L, Walss-Bass C, Lázaro-Muñoz G. Research comparing iPSC-derived neural organoids to ex vivo brain tissue of postmortem donors: identity after life? AJOB Neurosci. 2022;13:111–3.

    Article  PubMed  Google Scholar 

Download references

Funding

EFM is supported by the UTHealth/MD Anderson Cancer Center medical scientist training program T32GM129462. CWB is supported by grant R01DA044859.

Author information

Authors and Affiliations

  1. Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA

    Emily Frances Mendez & Consuelo Walss-Bass

Authors
  1. Emily Frances Mendez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Consuelo Walss-Bass
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

EFM and CWB wrote, edited, and approved the article.

Corresponding author

Correspondence to Consuelo Walss-Bass.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mendez, E.F., Walss-Bass, C. Postmortem-derived iPSC models in substance use disorders research. Neuropsychopharmacol. 49, 349–350 (2024). https://doi.org/10.1038/s41386-023-01703-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41386-023-01703-3

Search

Advanced search

Quick links