Adrenal insufficiency is a life-threatening disease, in which adrenocortical cells fail to produce adequate amount of steroid hormones, mostly glucocorticoids (cortisol) and mineralocorticoids (aldosterone). These hormones play an essential role in homeostasis, influencing the level of energy, fluids and salt. Adrenal insufficiency develops due to autoimmune disorders, hereditary factors, infection, metabolic or traumatic conditions, anti-cancer or antifungal therapy etc.
Here I demonstrate development of a transplantable bioartificial adrenal cortex as an option for the treatment of adrenal insufficiency:I List of figures 5
II List of abbreviations 6
1 Introduction to the topic 9
1.1 Motivation 9
1.2 Validation of bovine adrenocortical cells as a potential source for the establishment of a transplantable bioartificial adrenal cortex 11
1.3 Development of a 3D culture system through BAC encapsulation in sodium alginate 14
1.4 Altering the properties of bioartificial adrenal cortex by pharmacological agents 16
1.5 In vivo validation of the bioartificial adrenal cortex 18
1.6 Aim of dissertation 20
2 Publications 21
2.1 Balyura M, Gelfgat E, Ehrhart-Bornstein M, Ludwig B, Gendler Z, Barkai U, Zimerman B, Rotem A, Block NL, Schally AV, Bornstein SR. 2015. Transplantation of bovine adrenocortical cells encapsulated in alginate. Proc Natl Acad Sci U S A. 112(8):2527-32 22
2.2 Balyura M, Gelfgat E, Steenblock C, Androutsellis-Theotokis A, Ruiz-Babot G, Guasti L, Werdermann M, Ludwig B, Bornstein T, Schally AV, Brennand A, Bornstein SR. 2018. Expression of progenitor markers is associated with the functionality of a bioartificial adrenal cortex. PLoS One. 13(3):e0194643 32
2.3 Balyura M, Gelfgat E, Ullmann E, Ludwig B, Barnea ER, Bornstein SR. 2017. PreImplantation Factor (PIF*) regulates stress-induced adrenal steroidogenesis and anti-inflammatory cytokines: potential application for bioartificial adrenal transplant. Horm Metab Res. 50(2):168-174 48
3 Discussion and Outlook 57
4 Zusammenfassung 62
5 Summary 66
6 Additional Publications 69
7 References 71
8 Curriculum vitae 78
9 Acknowledgements 79
10 Declarations 80
10.1 Anlage 1. Erklärungen zur Eröffnung des Promotionsverfahrens 80
10.2 Anlage 2. Erklärung über die Einhaltung gesetzlicher Bestimmungen 8
