Scaffold-free cell sheet therapies - clinical advances, global approval landscapes, and strategic directions to address regenerative medicine barriers

Sep 29, 2026

Uploaded by Franzy

Cell sheet therapy has emerged as a transformative technology in regenerative medicine, providing scaffold-free constructs that preserve cell–cell junctions and extracellular matrix components. Compared with traditional cell delivery methods, cell sheets enable improved engraftment, survival, and integration after transplantation. Clinical translation is advancing across Japan, the United States, and South Korea, with multiple approved products. The review consolidates fabrication technologies, cell sources, indications, manufacturing standardization, and GMP-compliant safety frameworks. It also addresses remaining barriers including vascularization, scalable production, cost-effectiveness, and equitable access.

LanguageEnglish

CategoryHealthcare

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Pages24

Reading Time1 h 0 min

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Abstract

Introduction

Lin etal. Stem Cell Research & Therapy (2026) 17:5 [https://doi.org/10.1186/s13287-025-04818-0](https://doi.org/10.1186/s13287-025-04818-0) Stem Cell Research & Therapy REVIEW Open Access Scaffold-free cell sheet therapies: clinical advances, global approval landscapes, and strategic directions to address regenerative medicine barriers An Lin 1,2, Shengmeng Yuan 1, Cheng Liang 1, Fangjun Huo 1, Chao Yang3,4* and Weidong Tian 1,2* Abstract Cell sheet therapy has emerged as a transformative technology in regenerative medicine, providing scaffoldfree constructs that preserve cell–cell junctions and extracellular matrix components. Compared with traditional cell delivery methods, cell sheets enable improved engraftment, survival, and integration after transplantation. Recent years have witnessed remarkable progress in clinical translation, with several products approved in Japan, the United States, and South Korea. This review summarizes the current landscape of cell sheet therapies approved worldwide, focusing on their fabrication technologies, cell sources, and clinical indications. We highlight representative products such as JACE®, Nepic®, Ocural®, JACEMIN®, HeartSheet®, Epicel®, Holoderm®, Kaloderm®, and ZEVASKYN™, emphasizing their technological foundations and regulatory trajectories. Advances in temperatureresponsive culture surfaces, closed culture devices, and automated sheet manipulation have facilitated largescale and standardized manufacturing. Furthermore, the establishment of cell banks, donor eligibility screening, and Good Manufacturing Practice (GMP)-compliant processes ensure product consistency and safety. In parallel, regulatory frameworks in Japan, the United States, and South Korea have shaped the development paths of autologous and al logeneic products, with different strategies for approval, reimbursement, and long-term monitoring. Cell sheet-based regenerative therapies have already demonstrated clinical and commercial viability, offering novel treatment options for burns, ocular diseases, vitiligo, and cardiac conditions. Despite encouraging outcomes, challenges remain in vascularization, large-scale production, cost-effectiveness, and equitable patient access. Continued progress will depend on addressing biological limitations, optimizing manufacturing logistics, and harmonizing international regulations. Collectively, cell sheet therapies represent a pivotal step toward broader adoption of regenerative medicine in routine clinical practice. Keywords Cell sheet therapy, Regenerative medicine, Tissue engineering, Clinical translation, Regulatory approval, Global landscape *Correspondence: Chao Yang [yangchao1207@qq.com](yangchao1207@qq.com)[ ](yangchao1207@qq.com)Weidong Tian[drtwd@sina.com](drtwd@sina.com) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/l](vecommons.org/l)icenses/by-nc-nd/4.0/. Lin et al. Stem Cell Research & Therapy (202

FAQs

What is a cell sheet therapy and why is it important in regenerative medicine?

Cell sheet therapy uses scaffold-free, intact layers engineered in vitro. By preserving cell–cell junctions and extracellular matrix components, it supports better engraftment and therapeutic integration than traditional cell suspensions.

Which regions and regulatory frameworks influence the development of approved cell sheet products?

The review highlights regulatory paths shaped in Japan, the United States, and South Korea. These frameworks influence strategies for approval, reimbursement, and long-term monitoring of autologous and allogeneic products.

What manufacturing and quality systems help standardize cell sheet production?

Advances in temperature-responsive culture surfaces, closed culture devices, and automated sheet manipulation support scalable manufacturing. Cell banks, donor eligibility screening, and GMP-compliant processes help ensure consistency and safety.

Sep 29, 2026

Uploaded by Franzy