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REVIEW article

Front. Cell Dev. Biol.
Sec. Stem Cell Research
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1526306
This article is part of the Research Topic Studying Rare Diseases Using induced Pluripotent Stem Cell (iPSC)-based Model Systems View all 3 articles

Human-based complex in vitro models: their promise and potential for rare disease therapeutics

Provisionally accepted
Surat Parvatam Surat Parvatam 1*Francesca Pistollato Francesca Pistollato 2Lindsay Marshall Lindsay Marshall 3Fabia Furtmann Fabia Furtmann 2Devashree Jahagirdar Devashree Jahagirdar 4Mohua Chakraborty Choudhury Mohua Chakraborty Choudhury 5Sujata Mohanty Sujata Mohanty 6Harshita Mittal Harshita Mittal 1Saveetha M Saveetha M 7Rakesh Mishra Rakesh Mishra 7
  • 1 Humane Society International India, Hyderabad, India
  • 2 Humane Society International/Europe, Brussels, Belgium
  • 3 Humane Society of the United States, Washington D.C., District of Columbia, United States
  • 4 Indian Institute of Technology Bombay, Mumbai, Maharashtra, India
  • 5 Centre for Policy Research, Indian Institute of Science, Bangalore, India
  • 6 All India Institute of Medical Sciences, New Delhi, National Capital Territory of Delhi, India
  • 7 Tata Institute for Genetics and Society, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, Karnataka, India

The final, formatted version of the article will be published soon.

    Rare diseases affect a small percentage of an individual country's population; however, with over 7,000 in total, rare diseases represent a significant disease burden impacting up to 10% of the world's population. Despite this, there are no approved treatments for almost 95% of rare diseases, and the existing treatments are cost-intensive for the patients. More than 70% of rare diseases are genetic in nature, with patient-specific mutations. This calls for the need to have personalised and patient-specific preclinical models that can lead to effective, speedy, and affordable therapeutic options. Complex in vitro models (CIVMs), including those using induced pluripotent stem cells (iPSCs), organoids, and organs-on-chips are emerging as powerful human-based pre-clinical systems with the capacity to provide efficacy data enabling drugs to move into clinical trials. In this narrative review, we discuss how CIVMs are providing insights into biomedical research on rare diseases. We also discuss how these systems are being used in clinical trials to develop efficacy models for rare diseases. Finally, we propose recommendations on how human relevant CIVMs could be leveraged to increase translatability of basic, applied and nonclinical research outcomes in the field of rare disease therapeutics in developed as well as middle-and low-income countries.

    Keywords: Font, Italic Formatted, Italic Commented [SP2], REVIEWER 1 Minor Comment 1(1), Overall Section 2 has been revised for improving clarity and language now Commented [SP3], Reviewer 1 Minor Comment 1 (1), The sentence has now been rephrased

    Received: 11 Nov 2024; Accepted: 09 Jan 2025.

    Copyright: © 2025 Parvatam, Pistollato, Marshall, Furtmann, Jahagirdar, Chakraborty Choudhury, Mohanty, Mittal, M and Mishra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Surat Parvatam, Humane Society International India, Hyderabad, India

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.