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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)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Adrenal Gland ; Adrenal Insufficiency ; Adrenocortical Stem And Progenitor Cells ; Multicellular Spheroids ; Xenogeneic Transplantation; Bovine Adrenocortical-cells; Scid Mice; Tissue; Culture
ISSN (print) / ISBN 0908-665X
e-ISSN 1399-3089
Journal Xenotransplantation
Quellenangaben Volume: 30, Issue: 5, Pages: , Article Number: e12819 Supplement: ,
Publisher Wiley
Publishing Place Hoboken, NJ
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)
Grants Deutscher Akademischer Austauschdienst
Deutsche Forschungsgemeinschaft
TransCampus initiative between TU Dresden and King´s College London