Malyukov, M.* ; Gelfgat, E.* ; Ruiz-Babot, G.* ; Schmid, J.* ; Lehmann, S.* ; Spinas, G.* ; Beuschlein, F.* ; Hantel, C.* ; Reisch, N.* ; Nawroth, P.* ; Bornstein, S.R.* ; Steenblock, C.* ; Ludwig, B.
Transplantation of porcine adrenal spheroids for the treatment of adrenal insufficiency.
Xenotransplantation 30:e12819 (2023)
Primary adrenal insufficiency is a life-threatening disorder, which requires lifelong hormone replacement therapy. Transplantation of xenogeneic adrenal cells is a potential alternative approach for the treatment of adrenal insufficiency. For a successful outcome of this replacement therapy, transplanted cells should provide adequate hormone secretion and respond to adrenal physiological stimuli. Here, we describe the generation and characterization of primary porcine adrenal spheroids capable of replacing the function of adrenal glands in vivo. Cells within the spheroids morphologically resembled adult adrenocortical cells and synthesized and secreted adrenal steroid hormones in a regulated manner. Moreover, the embedding of the spheroids in alginate led to the formation of cellular elongations of steroidogenic cells migrating centripetally towards the inner part of the slab, similar to zona Fasciculata cells in the intact organ. Finally, transplantation of adrenal spheroids in adrenalectomized SCID mice reversed the adrenal insufficiency phenotype, which significantly improved animals' survival. Overall, such adrenal models could be employed for disease modeling and drug testing, and represent the first step toward potential clinical trials in the future.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Adrenal Gland ; Adrenal Insufficiency ; Adrenocortical Stem And Progenitor Cells ; Multicellular Spheroids ; Xenogeneic Transplantation; Bovine Adrenocortical-cells; Scid Mice; Tissue; Culture
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2023
Prepublished im Jahr
0
HGF-Berichtsjahr
2023
ISSN (print) / ISBN
0908-665X
e-ISSN
1399-3089
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 30,
Heft: 5,
Seiten: ,
Artikelnummer: e12819
Supplement: ,
Reihe
Verlag
Wiley
Verlagsort
Hoboken, NJ
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Pancreatic Islet Research (IPI)
POF Topic(s)
90000 - German Center for Diabetes Research
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-502600-007
Förderungen
Deutscher Akademischer Austauschdienst
Deutsche Forschungsgemeinschaft
TransCampus initiative between TU Dresden and King´s College London
Copyright
Erfassungsdatum
2023-10-06