Ebrahim NAA, Farghaly TA, Masaret GS, Alsaedi AMR, Soliman SMA. From laboratory to clinic: Bridging regulatory and manufacturing gaps in stem cell-based therapies. World J Stem Cells 2026; 18(5): 117591 [DOI: 10.4252/wjsc.v18.i5.117591]
Corresponding Author of This Article
Noura A A Ebrahim, Department of Oncologic Pathology, National Cancer Institute, Cairo University, 1st Kasr Al Ainy Street, Cairo 11796, Al Qāhirah, Egypt. npathologist@gmail.com
Research Domain of This Article
Biology
Article-Type of This Article
Minireviews
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World J Stem Cells. May 26, 2026; 18(5): 117591 Published online May 26, 2026. doi: 10.4252/wjsc.v18.i5.117591
From laboratory to clinic: Bridging regulatory and manufacturing gaps in stem cell-based therapies
Noura A A Ebrahim, Thoraya A Farghaly, Ghada S Masaret, Amani M R Alsaedi, Soliman M A Soliman
Noura A A Ebrahim, Department of Oncologic Pathology, National Cancer Institute, Cairo University, Cairo 11796, Al Qāhirah, Egypt
Thoraya A Farghaly, Ghada S Masaret, Department of Chemistry, Umm Al-Qura University, Makkah 21955, Saudi Arabia
Amani M R Alsaedi, Department of Chemistry, Collage of Science, Taif University, Taif 21944, Saudi Arabia
Soliman M A Soliman, Department of Chemistry, Faculty of Science, Cairo University, Cairo 12613, Al Qāhirah, Egypt
Co-corresponding authors: Noura A A Ebrahim and Soliman M A Soliman.
Author contributions: Ebrahim NAA and Soliman SMA contributed equally to the conceptualization and drafting of the manuscript, they contributed equally to this manuscript and are co-corresponding authors. Ebrahim NAA, Farghaly TA, Masaret GS, Alsaedi AMR, and Soliman SMA contributed in drafting and critical revision of the manuscript.
AI contribution statement: The manuscript text was written by the authors. Paperpal was used for language polishing only. No AI tool participate in design of the study or interpretation of its results. No images in the manuscript generated by AI.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Noura A A Ebrahim, Department of Oncologic Pathology, National Cancer Institute, Cairo University, 1st Kasr Al Ainy Street, Cairo 11796, Al Qāhirah, Egypt. npathologist@gmail.com
Received: December 11, 2025 Revised: February 5, 2026 Accepted: March 10, 2026 Published online: May 26, 2026 Processing time: 165 Days and 21.8 Hours
Abstract
Advanced therapy medicinal products (ATMPs), encompassing therapies derived from mesenchymal stem cells, induced pluripotent stem cells, and their extracellular vesicles, hold substantial transformative potential for clinical applications. However, their translation from bench to bedside and eventual commercialization is hindered by considerable scientific, manufacturing, and regulatory challenges. This review examines these challenges using a structured framework that synthesizes evidence from recent studies, international guidance documents, and regulatory agency reports. We provide an overview of the global regulatory environment and harmonization efforts that influence ATMP oversight, highlighting the frameworks established by major agencies and international initiatives. Technical discussions cover cell sourcing, scalable bioprocess engineering - including bioreactors, closed system technologies, and tangential flow filtration - product quality attributes, and real-time in-process monitoring, incorporating emerging artificial intelligence-driven process analytical technologies. Special focus is given to advanced considerations such as induced pluripotent stem cells tumorigenicity, emphasizing the risks posed by residual undifferentiated cells and the importance of sensitive assays and genetic integrity evaluation; mesenchymal stem cell-derived exosome production, with attention to scale-up strategies, isolation techniques, and quality control standards; global harmonization of good manufacturing practice and ATMP standards; and artificial intelligence-enabled process analytics for automated, closed-cell culture systems. The review further explores potency assays, product comparability, supply chain logistics, and forward-looking trends, including point-of-care manufacturing and digital twin approaches, aiming to equip researchers, developers, and regulators with strategies to advance ATMP development safely and efficiently, ensuring robust therapeutic efficacy and patient safety for next-generation cell and exosome therapies.
Core Tip: This review outlines the major scientific, regulatory, and manufacturing challenges that limit the clinical translation of stem cell-based advanced therapies. It highlights practical strategies - ranging from tumorigenicity assessment for induced pluripotent stem cells and good manufacturing practice-ready production of mesenchymal stem cell-derived exosomes to artificial intelligence-driven process monitoring and digital-twin modeling - that can support safer, scalable, and more consistent development of stem cell and extracellular-vesicle therapeutics.
