Expression of progenitor markers is associated with the functionality of a bioartificial adrenal cortex

PLoS One. 2018 Mar 29;13(3):e0194643. doi: 10.1371/journal.pone.0194643. eCollection 2018.

Abstract

Encapsulation of primary bovine adrenocortical cells in alginate is an efficacious model of a bioartificial adrenal cortex. Such a bioartificial adrenal cortex can be used for the restoration of lost adrenal function in vivo as well as for in vitro modeling of the adrenal microenvironment and for investigation of cell-cell interactions in the adrenals. The aim of this work was the optimization of a bioartificial adrenal cortex, that is the generation of a highly productive, self-regenerating, long-term functioning and immune tolerant bioartificial organ. To achieve this, it is necessary that adrenocortical stem and progenitor cells are present in the bioartificial gland, as these undifferentiated cells play important roles in the function of the mature gland. Here, we verified the presence of adrenocortical progenitors in cultures of bovine adrenocortical cells, studied the dynamics of their appearance and growth and determined the optimal time point for cell encapsulation. These procedures increased the functional life span and reduced the immunogenicity of the bioartificial adrenal cortex. This model allows the use of the luteinizing hormone-releasing hormone (LHRH) agonist triptorelin, the neuropeptide bombesin, and retinoic acid to alter cell number and the release of cortisol over long periods of time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex / cytology*
  • Adrenal Cortex / physiology
  • Adrenocorticotropic Hormone / pharmacology
  • Animals
  • Artificial Organs*
  • Biomarkers / metabolism
  • Cattle
  • Cell Culture Techniques
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression Regulation* / drug effects
  • Gene Expression Regulation, Enzymologic / drug effects
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Steroid Hydroxylases / genetics
  • Time Factors

Substances

  • Biomarkers
  • Adrenocorticotropic Hormone
  • Steroid Hydroxylases

Grants and funding

This work was in part supported by the International Fund Congenital Adrenal Hyperplasia (IFCAH) (to SRB), by the Deutsche Forschungsgemeinschaft (CRC-TRR 127 (to SRB and BL), CRC-TRR 205 (to SRB, BL and CS), IRTG 2251 (to SRB, BL and CS), and CRU 252 (to SRB and BL)), the German Academic Exchange Service (DAAD) (to GRB) and The TransCampus initiative between TU Dresden and King's College London (to SRB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.