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It begins with Wilhelm Roux\u2019s seminal experiments in the 1880s, followed by the pioneering efforts of Ross Granville Harrison, who initiated groundbreaking experiments that fundamentally shaped the landscape of cell culture in the early 20th century. Carrel\u2019s influential contributions, notably the immortalization of chicken heart cells, have marked a significant advancement in cell culture techniques. Subsequently, Johannes Holtfreter, Aron Moscona, and Joseph Leighton introduced methodological innovations in three-dimensional (3D) cell culture, initiated by Alexis Carrel, laying the groundwork for future consolidation and expansion of the use of 3D cell culture in different areas of biomedical sciences. The advent of induced pluripotent stem cells by Takahashi and Yamanaka in 2006 was revolutionary, enabling the reprogramming of differentiated cells into a pluripotent state. Since then, recent innovations have included spheroids, organoids, and organ-on-a-chip technologies, aiming to mimic the structure and function of tissues and organs in vitro, pushing the boundaries of biological modeling and disease understanding. In this review, we overview the history of cell culture shedding light on the main discoveries, pitfalls and hurdles that were overcome during the transition from 2D to 3D cell culture techniques. Finally, we discussed the future directions for cell culture research that may accelerate the development of more effective and personalized treatments.<\/jats:p>","DOI":"10.3390\/cells13242068","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T06:48:39Z","timestamp":1734331719000},"page":"2068","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["A Brief History of Cell Culture: From Harrison to Organs-on-a-Chip"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4620-5074","authenticated-orcid":false,"given":"Lincoln Gozzi","family":"Moro","sequence":"first","affiliation":[{"name":"Human Genome and Stem Cell Research Center, Institute of Biosciences, University of S\u00e3o Paulo\u2014USP, S\u00e3o Paulo 01246-904, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0733-1975","authenticated-orcid":false,"given":"Lucas Pires","family":"Guarnier","sequence":"additional","affiliation":[{"name":"Department of Genetic, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo\u2014USP, Ribeir\u00e3o Preto 14040-904, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6186-0424","authenticated-orcid":false,"given":"Maur\u00edcio Foga\u00e7a","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, University of S\u00e3o Paulo\u2014USP, S\u00e3o Paulo 01246-904, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Amanda Rodrigues","family":"Fracasso","sequence":"additional","affiliation":[{"name":"School of Dentistry, S\u00e3o Paulo State University\u2014UNESP, Ara\u00e7atuba 16015-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Aur\u00e9lio","family":"Lucio","sequence":"additional","affiliation":[{"name":"Graduate Program in Environment and Regional Development, University of Western S\u00e3o Paulo, Presidente Prudente 19050-920, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8895-652X","authenticated-orcid":false,"given":"Mateus Vidigal de","family":"Castro","sequence":"additional","affiliation":[{"name":"Human Genome and Stem Cell Research Center, Institute of Biosciences, University of S\u00e3o Paulo\u2014USP, S\u00e3o Paulo 01246-904, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9354-7280","authenticated-orcid":false,"given":"Marlon Lemos","family":"Dias","sequence":"additional","affiliation":[{"name":"Precision Medicine Research Center, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro\u2014UFRJ, Rio de Janeiro 21941-630, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6533-0850","authenticated-orcid":false,"given":"Francislaine Aparecida dos Reis","family":"L\u00edvero","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiometabolic Pharmacology, Federal University of Paran\u00e1\u2014UFPR, Curitiba 80035-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Tadeu","family":"Ribeiro-Paes","sequence":"additional","affiliation":[{"name":"Department of Genetic, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo\u2014USP, Ribeir\u00e3o Preto 14040-904, Brazil"},{"name":"Laboratory of Genetics and Cell Therapy (GenTe Cel), Department of Biotechnology, S\u00e3o Paulo State University\u2014UNESP, Assis 19806-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1152\/physiol.00036.2016","article-title":"Modeling Physiological Events in 2D vs. 3D Cell Culture","volume":"32","author":"Duval","year":"2017","journal-title":"Physiology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jedrzejczak-Silicka, M. 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