{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T11:02:28Z","timestamp":1761562948308,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Associazione Giovani Diabetici (AGD) BOLOGNA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Type 1 diabetes mellitus (T1DM) is a complex metabolic disease characterized by a massive loss of insulin-producing cells due to an autoimmune reaction. Currently, daily subcutaneous administration of exogenous insulin is the only effective treatment. Therefore, in recent years considerable interest has been given to stem cell therapy and in particular to the use of three-dimensional (3D) cell cultures to better reproduce in vivo conditions. The goal of this study is to provide a reliable cellular model that could be investigated for regenerative medicine applications for the replacement of insulin-producing cells in T1DM. To pursue this aim we create a co-culture spheroid of amniotic epithelial cells (AECs) and Wharton\u2019s jelly mesenchymal stromal cells (WJ-MSCs) in a one-to-one ratio. The resulting co-culture spheroids were analyzed for viability, extracellular matrix production, and hypoxic state in both early- and long-term cultures. Our results suggest that co-culture spheroids are stable in long-term culture and are still viable with a consistent extracellular matrix production evaluated with immunofluorescence staining. These findings suggest that this co-culture may potentially be differentiated into endo-pancreatic cells for regenerative medicine applications in T1DM.<\/jats:p>","DOI":"10.3390\/bioengineering10020189","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T03:47:33Z","timestamp":1675309653000},"page":"189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Characterization of Perinatal Stem Cell Spheroids for the Development of Cell Therapy Strategy"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0424-9287","authenticated-orcid":false,"given":"Francesca","family":"Paris","sequence":"first","affiliation":[{"name":"Unit of Histology, Embryology and Applied Biology, Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6644-5828","authenticated-orcid":false,"given":"Pasquale","family":"Marrazzo","sequence":"additional","affiliation":[{"name":"Unit of Histology, Embryology and Applied Biology, Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5591-7663","authenticated-orcid":false,"given":"Valeria","family":"Pizzuti","sequence":"additional","affiliation":[{"name":"Unit of Histology, Embryology and Applied Biology, Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cosetta","family":"Marchionni","sequence":"additional","affiliation":[{"name":"Unit of Histology, Embryology and Applied Biology, Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maura","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8510-2780","authenticated-orcid":false,"given":"Martina","family":"Michelotti","sequence":"additional","affiliation":[{"name":"Unit of Histology, Embryology and Applied Biology, Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biljana","family":"Petrovic","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy"},{"name":"Center for Applied Biomedical Research (CRBA), University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3130-5168","authenticated-orcid":false,"given":"Elisabetta","family":"Ciani","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Science, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuliana","family":"Simonazzi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy"},{"name":"Obstetrics Unit, Department of Obstetrics and Gynecology, IRCCS Azienda Ospedaliero-Universitaria Sant\u2019Orsola, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0379-9562","authenticated-orcid":false,"given":"Andrea","family":"Pession","sequence":"additional","affiliation":[{"name":"Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Bonsi","sequence":"additional","affiliation":[{"name":"Unit of Histology, Embryology and Applied Biology, Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5315-0104","authenticated-orcid":false,"given":"Francesco","family":"Alviano","sequence":"additional","affiliation":[{"name":"Unit of Histology, Embryology and Applied Biology, Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S0140-6736(06)68341-4","article-title":"Type 1 diabetes","volume":"367","author":"Daneman","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Paris, F., Pizzuti, V., Marrazzo, P., Pession, A., Alviano, F., and Bonsi, L. 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