Spheroids derived from the stromal vascular fraction of adipose tissue self-organize in complex adipose organoids and secrete leptin

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dc.article.number70
dc.catalogadorcrc
dc.contributor.authorRobledo Plaza, Fermín Alberto
dc.contributor.authorGonzález Hódar, Lila Alejandra
dc.contributor.authorTapia, Pablo
dc.contributor.authorFigueroa Toledo, Ana Maria
dc.contributor.authorEzquer, Fernando
dc.contributor.authorCortes Mora, Victor Antonio
dc.date.accessioned2023-04-10T17:22:14Z
dc.date.available2023-04-10T17:22:14Z
dc.date.issued2023
dc.date.updated2023-04-09T00:03:13Z
dc.description.abstractAbstract Background Adipose tissue-derived stromal vascular fraction (SVF) harbors multipotent cells with potential therapeutic relevance. We developed a method to form adipose spheroids (AS) from the SVF with complex organoid structure and enhanced leptin secretion upon insulin stimulation. Methods SVF was generated from the interscapular brown adipose tissue of newborn mice. Immunophenotype and stemness of cultured SVF were determined by flow cytometry and in vitro differentiation, respectively. Spheroids were generated in hanging drops and non-adherent plates and compared by morphometric methods. The adipogenic potential was compared between preadipocyte monolayers and spheroids. Extracellular leptin was quantified by immunoassay. Lipolysis was stimulated with isoprenaline and quantified by colorimetric methods. AS viability and ultrastructure were determined by confocal and transmission electron microscopy analyses. Results Cultured SVF contained Sca1 + CD29 + CD44 + CD11b- CD45- CD90- cells with adipogenic and chondrogenic but no osteogenic potential. Culture on non-adherent plates yielded the highest quantity and biggest size of spheroids. Differentiation of AS for 15 days in a culture medium supplemented with insulin and rosiglitazone resulted in greater Pparg, Plin1, and Lep expression compared to differentiated adipocytes monolayers. AS were viable and maintained leptin secretion even in the absence of adipogenic stimulation. Glycerol release after isoprenaline stimulation was higher in AS compared to adipocytes in monolayers. AS were composed of outer layers of unilocular mature adipocytes and an inner structure composed of preadipocytes, immature adipocytes and an abundant loose extracellular matrix. Conclusion Newborn mice adipose SVF can be efficiently differentiated into leptin-secreting AS. Prolonged stimulation with insulin and rosiglitazone allows the formation of structurally complex adipose organoids able to respond to adrenergic lipolytic stimulation.
dc.fechaingreso.objetodigital2023-04-11
dc.format.extent19 páginas
dc.fuente.origenAutoarchivo
dc.identifier.citationRobledo, F., González-Hodar, L., Tapia, P. et al. Spheroids derived from the stromal vascular fraction of adipose tissue self-organize in complex adipose organoids and secrete leptin. Stem Cell Res Ther 14, 70 (2023). https://doi.org/10.1186/s13287-023-03262-2
dc.identifier.doi10.1186/s13287-023-03262-2
dc.identifier.issn1757-6512
dc.identifier.urihttps://doi.org/10.1186/s13287-023-03262-2
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/66731
dc.information.autorucFacultad de ciencias biológicas; Robledo Plaza Fermín Alberto;s/i ;131967
dc.information.autorucEscuela de medicina; González Hódar Lila Alejandra; s/i;156090
dc.information.autorucEscuela de Medicina;Figueroa Toledo, Ana Maria; s/i; 237627
dc.information.autorucEscuela de medicina;Cortes Mora Victor Antonio;0000-0002-1658-0965; 7576
dc.language.isoen
dc.nota.accesoContenido completo
dc.revistaStem Cell Research & Therapy
dc.rightsacceso abierto
dc.rights.holderThe Author(s)
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectOrganoid
dc.subjectSpheroid
dc.subjectAdipose tissue
dc.subjectLeptin
dc.subjectAdipogenesis
dc.subject.ddc610
dc.subject.deweyMedicina y salud
dc.titleSpheroids derived from the stromal vascular fraction of adipose tissue self-organize in complex adipose organoids and secrete leptin
dc.typeartículo
dc.volumen14
sipa.codpersvinculados131967
sipa.codpersvinculados156090
sipa.codpersvinculados237627
sipa.codpersvinculados7576
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