{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T05:37:21Z","timestamp":1792993041740,"version":"4.5.0"},"reference-count":79,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Education and Science of the Russian Federation","award":["FURG-2025-0028"],"award-info":[{"award-number":["FURG-2025-0028"]}],"id":[{"id":"https:\/\/ror.org\/00ghqgy32","id-type":"ROR","asserted-by":"crossref"}]},{"award":["FURG-2025-0028"],"award-info":[{"award-number":["FURG-2025-0028"]}],"id":[{"id":"https:\/\/ror.org\/00ghqgy32","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Cell and tissue products used in regenerative medicine are classified differently across jurisdictions according to processing, intended use, and manufacturing setting. This review compares regulatory approaches to products including bone marrow aspirate concentrate, adipose-derived stromal vascular fraction (SVF), microfragmented adipose tissue, nanofat, amniotic products, and cartilage-derived products, with particular attention to their implications for mesenchymal stromal cell (MSC)-based interventions. Legislation, regulatory guidance, enforcement documents, judicial decisions, and scientific publications were examined for the United States, European Union, Russian Federation, Eurasian Economic Union, selected Asian countries, and Arab jurisdictions. In the United States, minimal manipulation and homologous use are central classification criteria. In the European Union, substantial manipulation or use for a different essential function may bring a product within the advanced therapy medicinal product framework. Russian and Eurasian rules require distinction among biomedical cell products, individualized products, medicinal products, transplantation materials, and medical procedures. SVF is a heterogeneous cell population, while microfragmented adipose tissue retains tissue structures. Neither should be equated with an isolated or culture-expanded MSC preparation solely because it contains stromal cells. Regulatory assessment and interpretation of clinical evidence require clear reporting of product composition, processing, claimed mechanism of action, and manufacturing conditions.<\/jats:p>","DOI":"10.3390\/bioengineering13101235","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:12:21Z","timestamp":1792638741000},"page":"1235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["International Regulatory Classification of Minimally Manipulated and Borderline Cell and Tissue Products: Implications for Mesenchymal Stromal Cell-Based Interventions"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8888-8395","authenticated-orcid":false,"given":"Airat","family":"Bilyalov","sequence":"first","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9179-515X","authenticated-orcid":false,"given":"Nikita","family":"Filatov","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Iashina","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Briko","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Chibizov","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Nadelyaeva","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5989-9044","authenticated-orcid":false,"given":"Alexey","family":"Tikhomirov","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Petrikina","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2220-9695","authenticated-orcid":false,"given":"Viatcheslav","family":"Vasilyev","sequence":"additional","affiliation":[{"name":"Kazan State Medical Academy, Branch Campus of the Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russian Federation, Kazan 420012, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8389-3841","authenticated-orcid":false,"given":"Roman","family":"Deev","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Eremin","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Kotenko","sequence":"additional","affiliation":[{"name":"Petrovsky National Research Centre of Surgery, Moscow 117418, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"ref_1","unstructured":"U.S. Food and Drug Administration (2026, June 22). Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use. Guidance for Industry and Food and Drug Administration Staff, Available online: https:\/\/www.fda.gov\/media\/109176\/download."},{"key":"ref_2","unstructured":"Electronic Code of Federal Regulations (2026, June 22). Title 21, Chapter I, Subchapter L, Part 1271. Human Cells, Tissues, and Cellular and Tissue-Based Products, Available online: https:\/\/www.ecfr.gov\/current\/title-21\/chapter-I\/subchapter-L\/part-1271."},{"key":"ref_3","unstructured":"European Parliament, and Council of the European Union (2007). Regulation (EC) No. 1394\/2007 of the European Parliament and of the Council of 13 November 2007 on Advanced Therapy Medicinal Products and Amending Directive 2001\/83\/EC and Regulation (EC) No. 726\/2004. Off. J. Eur. Union, L324, 121\u2013137. Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX:32007R1394."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Iglesias-Lopez, C., Agust\u00ed, A., Obach, M., and Vallano, A. (2019). Regulatory Framework for Advanced Therapy Medicinal Products in Europe and United States. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00921"},{"key":"ref_5","unstructured":"Russian Federation (2026, June 22). Federal Law No. 466-FZ of 4 August 2023 on Amendments to Article 4 of the Federal Law \u2018On Circulation of Medicinal Products\u2019 and the Federal Law \u2018On Biomedical Cell Products\u2019. Available online: https:\/\/www.alta.ru\/tamdoc\/23fz0466\/."},{"key":"ref_6","unstructured":"Government of the Russian Federation (2026, June 22). Decree No. 384 of 28 March 2024 on Approval of the Rules for the Circulation of Biomedical Cell Products Intended for Individual Medical Prescription and Specially Manufactured for an Individual Patient in a Medical Organization. Available online: https:\/\/www.consultant.ru\/document\/cons_doc_LAW_473334\/."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.healthpol.2020.05.004","article-title":"Regenerative Medicine Regulatory Policies: A Systematic Review and International Comparison","volume":"124","author":"Qiu","year":"2020","journal-title":"Health Policy"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jcyt.2020.11.008","article-title":"Comparison of Regulatory Pathways for the Approval of Advanced Therapies in the European Union and the United States","volume":"23","author":"Obach","year":"2021","journal-title":"Cytotherapy"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.stem.2014.01.013","article-title":"MSC-Based Product Characterization for Clinical Trials: An FDA Perspective","volume":"14","author":"Mendicino","year":"2014","journal-title":"Cell Stem Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.jcyt.2025.06.005","article-title":"Defining minimal criteria for peer-reviewed reporting of mesenchymal stromal cell clinical trials for autoimmune diseases","volume":"27","author":"Davies","year":"2025","journal-title":"Cytotherapy"},{"key":"ref_11","unstructured":"European Medicines Agency (2026, June 22). Guideline on Human Cell-Based Medicinal Products. Available online: https:\/\/www.ema.europa.eu\/en\/human-cell-based-medicinal-products-scientific-guideline."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tang, X., Cai, L., Meng, Y., Xu, J., Lu, C., and Yang, J. (2021). Indicator Regularized Non-Negative Matrix Factorization Method-Based Drug Repurposing for COVID-19. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.603615"},{"key":"ref_13","unstructured":"Council of the Eurasian Economic Commission (2026, June 22). Decision No. 78 of 3 November 2016 on the Rules for Registra-tion and Expert Evaluation of Medicinal Products for Human Use. Available online: https:\/\/docs.eaeunion.org\/docs\/ru-ru\/01411916\/cncd_21112016_78."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e13217","DOI":"10.1111\/cpr.13217","article-title":"Development and Regulation of Stem Cell-Based Therapies in China","volume":"55","author":"Gao","year":"2022","journal-title":"Cell Prolif."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/978-3-031-34567-8_11","article-title":"Regulatory Oversight of Cell, Tissue, and Gene Therapy Products in Singapore","volume":"1430","author":"Ong","year":"2023","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_16","unstructured":"European Medicines Agency (2026, June 22). Advanced Therapy Medicinal Products: Overview. Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/advanced-therapy-medicinal-products-overview."},{"key":"ref_17","unstructured":"European Parliament, and Council of the European Union (2001). Directive 2001\/83\/EC of the European Parliament and of the Council of 6 November 2001 on the Community Code Relating to Medicinal Products for Human Use. Off. J. Eur. Communities, L311, 67\u2013128. Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX:32001L0083."},{"key":"ref_18","unstructured":"U.S. Food and Drug Administration (2026, June 22). Same Surgical Procedure Exception Under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception. Guidance for Industry, Available online: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/same-surgical-procedure-exception-under-21-cfr-127115b-questions-and-answers-regarding-scope."},{"key":"ref_19","unstructured":"Russian Federation (2026, June 22). Federal Law No. 180-FZ of 23 June 2016 on Biomedical Cell Products. Available online: https:\/\/base.garant.ru\/71427992\/."},{"key":"ref_20","unstructured":"Council of the Eurasian Economic Commission (2026, June 22). Decision No. 89 of 3 November 2016 on Approval of the Rules for Conducting Studies of Biological Medicinal Products of the Eurasian Economic Union. Available online: https:\/\/docs.eaeunion.org\/docs\/ru-ru\/01411930\/cncd_21112016_89."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1177\/2168479014526877","article-title":"New Governmental Regulatory System for Stem Cell-Based Therapies in Japan","volume":"48","author":"Hara","year":"2014","journal-title":"Ther. Innov. Regul. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.reth.2016.04.001","article-title":"Japan\u2019s Challenges of Translational Regenerative Medicine: Act on the Safety of Regenerative Medicine","volume":"4","author":"Tobita","year":"2016","journal-title":"Regen. Ther."},{"key":"ref_23","unstructured":"Pharmaceuticals and Medical Devices Agency (2026, June 22). Regenerative Medical Products. Available online: https:\/\/www.pmda.go.jp\/english\/review-services\/reviews\/0003.html."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s13045-022-01354-9","article-title":"Gene and cell therapies in China: Booming landscape under dual-track regulation","volume":"15","author":"Yin","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.jcyt.2024.04.070","article-title":"The Evolving Regulatory System of Advanced Therapy Medicinal Products in China: A Documentary Analysis Using the World Health Organization Global Benchmarking Tool Standards","volume":"26","author":"Shi","year":"2024","journal-title":"Cytotherapy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"791","DOI":"10.2217\/rme-2019-0069","article-title":"Regulations on Cell Therapy Products in China: A Brief History and Current Status","volume":"14","author":"Li","year":"2019","journal-title":"Regen. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104889","DOI":"10.1016\/j.phrs.2020.104889","article-title":"Regulatory Oversight of Cell Therapy in China: Government\u2019s Efforts in Patient Access and Therapeutic Innovation","volume":"158","author":"Wu","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_28","unstructured":"State Council of the People\u2019s Republic of China (2026, October 13). Regulations on the Administration of Clinical Research and Clinical Application of New Biomedical Technologies. State Council Order No. 818, 28 September 2025; Effective 1 May 2026, Available online: https:\/\/www.mee.gov.cn\/zcwj\/gwywj\/202510\/t20251011_1129176.shtml."},{"key":"ref_29","unstructured":"Korea Legislation Research Institute (2026, June 22). Act on the Safety of and Support for Advanced Regenerative Medicine and Advanced Biological Products. Available online: https:\/\/elaw.klri.re.kr\/eng_mobile\/viewer.do?hseq=68827&key=37&type=part."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kim, D.S., and Bae, S. (2022). Impact and Challenges of Enactment for Advanced Regenerative Medicine in South Korea. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.972865"},{"key":"ref_31","unstructured":"Ministry of Food and Drug Safety (2026, June 22). Pre-Announcement of Legislation: Proposals for the Establishment of Lower Statutes of the Act on the Safety of and Support for Advanced Regenerative Medicine and Advanced Biopharmaceuticals. Available online: https:\/\/www.mfds.go.kr\/eng\/brd\/m_61\/view.do?seq=10."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1186\/s13287-024-04065-9","article-title":"Comparative Analysis of Regulations and Studies on Stem Cell Therapies: Focusing on Induced Pluripotent Stem Cell-Based Treatments","volume":"15","author":"Song","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_33","unstructured":"Health Sciences Authority (2026, June 22). Cell, Tissue and Gene Therapy Products: Regulatory Overview, Available online: https:\/\/www.hsa.gov.sg\/ctgtp\/overview\/regulatory-overview."},{"key":"ref_34","unstructured":"Singapore Statutes Online (2026, June 22). Health Products (Cell, Tissue and Gene Therapy Products) Regulations 2021, Available online: https:\/\/sso.agc.gov.sg\/SL\/HPA2007-S104-2021."},{"key":"ref_35","unstructured":"Saudi Food and Drug Authority (2026, June 22). Guideline on Classification of Advanced Therapy Medicinal Products, Available online: https:\/\/www.sfda.gov.sa\/en\/guide\/sfda-guideline-classification-advanced-therapy-medicinal-products."},{"key":"ref_36","unstructured":"Emirates Drug Establishment (2026, October 13). Classification of a Medical Product, Available online: https:\/\/www.ede.gov.ae\/en\/w\/classification-of-a-product."},{"key":"ref_37","unstructured":"Dubai Health Authority (2026, June 22). Standards for Stem Cells and Regenerative Medicine, Available online: https:\/\/www.dha.gov.ae\/uploads\/022025\/Standards%20for%20Stem%20Cells%20and%20Regenerative%20Medicine202522994.pdf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2174\/011574888X372893250804112424","article-title":"Regulatory Prospects for Stem Cell in Clinical Trials: UAE, US, and India","volume":"21","author":"Reddy","year":"2025","journal-title":"Curr. Stem Cell Res. Ther."},{"key":"ref_39","unstructured":"U.S. Food and Drug Administration (2026, October 13). Cellular & Gene Therapy Products, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products."},{"key":"ref_40","unstructured":"European Medicines Agency (2026, October 13). Committee for Advanced Therapies (CAT). Available online: https:\/\/www.ema.europa.eu\/en\/committees\/committee-advanced-therapies-cat."},{"key":"ref_41","unstructured":"Federal Service for Surveillance in Healthcare (Roszdravnadzor) (2026, October 13). Biomedical Cell Products, Available online: https:\/\/roszdravnadzor.gov.ru\/biomedical."},{"key":"ref_42","unstructured":"Okudaira, S. (2023, January 1). Updates of Regulations & Recent Trends in Regenerative Medical Products in Japan. Presented at the 6th India-Japan Medical Products Regulatory Symposium, Virtual. Available online: https:\/\/www.pmda.go.jp\/files\/000250262.pdf."},{"key":"ref_43","first-page":"1735242","article-title":"Minimally Manipu-lated Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Systematic Review of Clinical Evidence","volume":"2019","author":"Vandenbulcke","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"23259671241296555","DOI":"10.1177\/23259671241296555","article-title":"Bone Marrow Aspirate Concentrate Injections for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials","volume":"12","author":"Han","year":"2024","journal-title":"Orthop. J. Sports Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s13287-017-0598-y","article-title":"Adipose Tissue-Derived Stromal Vascular Fraction in Regenerative Medicine: A Brief Review on Biology and Translation","volume":"8","author":"Bora","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Senesi, L., De Francesco, F., Farinelli, L., Manzotti, S., Gagliardi, G., Papalia, G.F., Riccio, M., and Gigante, A. (2019). Me-chanical and Enzymatic Procedures to Isolate the Stromal Vascular Fraction from Adipose Tissue: Preliminary Re-sults. Front. Cell Dev. Biol., 7.","DOI":"10.3389\/fcell.2019.00088"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1111\/wrr.13228","article-title":"Comparing Mechanical and Enzymatic Isolation Procedures to Isolate Adipose-Derived Stromal Vascular Fraction: A Systematic Review","volume":"32","author":"Uguten","year":"2024","journal-title":"Wound Repair Regen."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s13770-020-00313-0","article-title":"Not Stromal Vascular Fraction (SVF) or Nanofat, but Total Stromal-Cells (TOST): A New Definition. Systemic Review of Mechanical Stromal-Cell Extraction Techniques","volume":"18","author":"Copcu","year":"2021","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Cicione, C., Vadal\u00e0, G., Di Giacomo, G., Tilotta, V., Ambrosio, L., Russo, F., Zampogna, B., Cannata, F., Papalia, R., and Denaro, V. (2023). Micro-Fragmented and Nanofat Adipose Tissue Derivatives: In Vitro Qualitative and Quantitative Analysis. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.911600"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.3727\/096368912X657855","article-title":"A New Nonenzymatic Method and Device to Obtain a Fat Tissue Derivative Highly En-riched in Pericyte-Like Elements by Mild Mechanical Forces from Human Lipoaspirates","volume":"22","author":"Bianchi","year":"2013","journal-title":"Cell Transplant."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1002\/sctm.19-0166","article-title":"Intraoperative Strategies for Minimal Manipulation of Autologous Adipose Tissue for Cell- and Tissue-Based Therapies: Concise Review","volume":"8","author":"Trivisonno","year":"2019","journal-title":"Stem Cells Transl. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1002\/sctm.18-0285","article-title":"Functional Outcomes Following Microfragmented Adipose Tissue versus Bone Marrow Aspirate Concentrate Injections for Symptomatic Knee Osteoarthritis","volume":"8","author":"Mautner","year":"2019","journal-title":"Stem Cells Transl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1097\/PRS.0b013e31829fe1b0","article-title":"Nanofat Grafting: Basic Research and Clinical Applications","volume":"132","author":"Tonnard","year":"2013","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Girard, P., Savineau, C., Gaillard, J., Perez, M., Bosc, R., Hersant, B., and Meningaud, J.P. (2022). Modified Nanofat Grafting: Stromal Vascular Fraction Simple Mechanical Dissociation for Stem Cell-Based Therapy. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.895735"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"ojz028","DOI":"10.1093\/asjof\/ojz028","article-title":"Cellular Optimization of Nanofat: Comparison of Two Nanofat Processing Devices in Terms of Cell Count and Viability","volume":"1","author":"Cohen","year":"2019","journal-title":"Aesthetic Surg. J. Open Forum"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.4252\/wjsc.v13.i11.1733","article-title":"Nanofat: A Therapeutic Paradigm in Re-generative Medicine","volume":"13","author":"Jeyaraman","year":"2021","journal-title":"World J. Stem Cells"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"NP1557","DOI":"10.1093\/asj\/sjab033","article-title":"Comparison of Microfat, Nanofat, and Extracellular Matrix\/Stromal Vascular Fraction Gel for Skin Rejuvenation: Basic Research and Clinical Applications","volume":"41","author":"Yang","year":"2021","journal-title":"Aesthetic Surg. J."},{"key":"ref_58","unstructured":"U.S. Food and Drug Administration (2026, June 22). BioStem Life Sciences. Warning Letter 673788, Available online: https:\/\/www.fda.gov\/inspections-compliance-enforcement-and-criminal-investigations\/warning-letters\/biostem-life-sciences-673788-01172025."},{"key":"ref_59","unstructured":"U.S. Food and Drug Administration (2026, June 22). Amnio Technology, LLC. Warning Letter 646460, Available online: https:\/\/www.fda.gov\/inspections-compliance-enforcement-and-criminal-investigations\/warning-letters\/amnio-technology-llc-646460-10012024."},{"key":"ref_60","unstructured":"U.S. Food and Drug Administration (2026, June 22). MACI: Autologous Cultured Chondrocytes on Porcine Collagen Membrane, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/maci-autologous-cultured-chondrocytes-porcine-collagen-membrane."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1097\/JSA.0000000000000079","article-title":"Autologous Chondrocyte Implantation with Collagen Membrane","volume":"23","author":"Gillogly","year":"2015","journal-title":"Sports Med. Arthrosc. Rev."},{"key":"ref_62","unstructured":"European Medicines Agency (2026, June 22). MACI: EPAR, Public Assessment Report. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/assessment-report\/maci-epar-public-assessment-report_en.pdf."},{"key":"ref_63","unstructured":"European Parliament, and Council of the European Union (2004). Directive 2004\/23\/EC of the European Parliament and of the Council of 31 March 2004 on Setting Standards of Quality and Safety for the Donation, Procurement, Testing, Processing, Preservation, Storage and Distribution of Human Tissues and Cells. Off. J. Eur. Union, L102, 48\u201358. Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX:32004L0023."},{"key":"ref_64","unstructured":"International Society for Stem Cell Research (2026, June 22). Guidelines for Stem Cell Research and Clinical Translation. Available online: https:\/\/www.isscr.org\/guidelines."},{"key":"ref_65","unstructured":"International Society for Stem Cell Research (2026, June 22). Standards for Human Stem Cell Use in Research: Reporting. Available online: https:\/\/www.isscr.org\/basic-research-standards\/reporting."},{"key":"ref_66","unstructured":"U.S. Food and Drug Administration (2026, October 13). FDA Approves Remestemcel-L-rknd for Steroid-Refractory Acute Graft Versus Host Disease in Pediatric Patients, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-remestemcel-l-rknd-steroid-refractory-acute-graft-versus-host-disease-pediatric."},{"key":"ref_67","unstructured":"U.S. Food and Drug Administration (2026, October 13). RYONCIL (Remestemcel-L-rknd) Suspension for Intravenous Infusion. Prescribing Information, Available online: https:\/\/www.fda.gov\/media\/184603\/download."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/S0140-6736(16)31203-X","article-title":"Expanded Allogeneic Adipose-Derived Mesenchymal Stem Cells (Cx601) for Complex Perianal Fistulas in Crohn\u2019s Disease: A Phase 3 Randomised, Double-Blind Controlled Trial","volume":"388","author":"Colombel","year":"2016","journal-title":"Lancet"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1053\/j.gastro.2025.12.033","article-title":"Darvadstrocel in Patients With Crohn\u2019s Disease With Complex Perianal Fistulas: The ADMIRE CD II Phase 3 Randomized Trial","volume":"170","author":"Colombel","year":"2026","journal-title":"Gastroenterology"},{"key":"ref_70","unstructured":"European Medicines Agency (2026, October 13). Alofisel (Darvadstrocel): Withdrawal from the EU Market as Its Clinical Benefit Is No Longer Demonstrated to Justify Its Continued Use. Direct Healthcare Professional Communication. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/dhpc\/direct-healthcare-professional-communication-dhpc-alofisel-darvadstrocel-withdrawal-eu-market-its-clinical-benefit-no-longer-demonstrated-justify-its-continued-use_en.pdf."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3120","DOI":"10.1038\/s41591-023-02632-w","article-title":"Cell-Based versus Corticosteroid Injections for Knee Pain in Osteoarthritis: A Randomized Phase 3 Trial","volume":"29","author":"Mautner","year":"2023","journal-title":"Nat. Med."},{"key":"ref_72","unstructured":"U.S. Food and Drug Administration (2026, June 22). Important Patient and Consumer Information About Regenerative Medicine Therapies, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/consumers-biologics\/important-patient-and-consumer-information-about-regenerative-medicine-therapies."},{"key":"ref_73","unstructured":"European Medicines Agency (2026, June 22). Guideline on Quality, Non-Clinical and Clinical Requirements for Investigational Advanced Therapy Medicinal Products in Clinical Trials. Available online: https:\/\/www.ema.europa.eu\/en\/guideline-quality-non-clinical-clinical-requirements-investigational-advanced-therapy-medicinal-products-clinical-trials-scientific-guideline."},{"key":"ref_74","unstructured":"U.S. Food and Drug Administration (2026, June 22). Potency Assurance for Cellular and Gene Therapy Products. Draft Guidance for Industry, Available online: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/potency-assurance-cellular-and-gene-therapy-products."},{"key":"ref_75","unstructured":"United States Court of Appeals for the Ninth Circuit (2026, June 22). United States v. California Stem Cell Treatment Center, Inc., No. 22-56014. Opinion Filed 27 September 2024, Available online: https:\/\/cdn.ca9.uscourts.gov\/datastore\/opinions\/2024\/09\/27\/22-56014.pdf."},{"key":"ref_76","unstructured":"Supreme Court of the United States (2026, June 22). Docket No. 24-1189, California Stem Cell Treatment Center, Inc. v. United States, Available online: https:\/\/www.supremecourt.gov\/docket\/docketfiles\/html\/public\/24-1189.html."},{"key":"ref_77","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (2026, June 22). Cell and Gene Therapy Discussion Group Recommendation Paper: Proposed Future ICH Guidelines for Advanced Therapy Medicinal Products. Available online: https:\/\/database.ich.org\/sites\/default\/files\/ICH_CGTDG_RecommendationPaper_2025_1201_MCEndorsed_2025_1117.pdf."},{"key":"ref_78","unstructured":"European Commission (2026, June 22). Proposal for a Directive of the European Parliament and of the Council on the Union Code Relating to Medicinal Products for Human Use, and Repealing Directive 2001\/83\/EC and Directive 2009\/35\/EC. COM(2023) 192 Final. Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX:52023PC0192."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.reth.2025.02.007","article-title":"Regulatory Insights on Gene Therapies, Adeno-Associated Virus-Based Gene Therapies and Quality Control Testing of Regenerative Medicine Products through the 7th Asia Partnership Conference of Regenerative Medicine","volume":"29","author":"Tsurumaki","year":"2025","journal-title":"Regen. Ther."}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/10\/1235\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T05:15:28Z","timestamp":1792991728000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/10\/1235"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,21]]},"references-count":79,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["bioengineering13101235"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering13101235","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,21]]}}}