Chromaffin Progenitor Cells from the Adrenal Medulla

Abstract

Chromaffin cells of the adrenal medulla are neural crest-derived cells of the sympathoadrenal lineage. Different lines of evidence suggest the existence of a subpopulation of proliferation-competent progenitor cells even in the adult state. The identification of sympathoadrenal progenitors in the adrenal would greatly enhance the understanding of adrenal physiology and their potential role in adrenal pathogenesis. Isolation and differentiation of these progenitor cells in culture would provide a tool to understand their development in vitro. Furthermore, due to the close relation to sympathetic neurons, these cells might provide an expandable source of cells for cell therapy in the treatment of neurodegenerative diseases. We therefore aim to establish protocols for the efficient isolation, enrichment and differentiation of chromaffin progenitor cells to dopaminergic neurons in culture.

Adrenal cortical and chromaffin stem cells: Is there a common progeny related to stress adaptation?

“…Furthermore, it is also unclear, which types of progenitors or stem cells that persist and are maintained in the postnatal adrenal. It has been suggested that a subpopulation of proliferation competent progenitor cells continues to exist in the adult adrenal medulla Ehrhart-Bornstein et al, 2010). In addition to the adaptation to physiological needs, these progenitor cells may be involved in the development of stress-related hyper activation and hyperplasia of the adrenal and potentially in tumor development (Molatore et al, 2010;Powers et al, 2007).…”

“…We have for the first time been able to prove the existence of proliferation and differentiation-competent sympathoadrenal progenitor cells within the adult adrenal medulla and have established methods for their isolation from bovine (Chung et al, 2009;Ehrhart-Bornstein et al, 2010;Masjkur et al, 2014) and human (Santana et al, 2012) adrenals. Under low-attachment cell culture conditions, where adherence to the culture dish is prevented, these cells express progenitor markers, have in vitro self-renewing capacity and grow in spheres, which we called chromospheres.…”

“…The adrenal medulla secreting catecholamines derives from the neural crest, while the adrenal cortex producing corticosteroids develops from the intermediate mesoderm. Both the adrenal cortex and medulla are very dynamic organs involved in the body's adaptation to stress and specific adult progenitor/stem cells are found in both parts, where they contribute to the renewal of organ-specific cells (Ehrhart-Bornstein et al, 2010;Walczak and Hammer, 2015).…”

Chromaffin cell transplants: From the lab to the clinic

“…As an alternative method to replenish DA in PD, chromaffin cells grafts have been proposed due to their ability to synthesize and release catecholamines. Nevertheless, the majority of chromaffin cells in the adult adrenal medulla produce epinephrine while only 1% of the population produces dopamine (Ehrhart-Bornstein et al, 2010).…”

“…This protocol significantly increased the Table 2 Trials of adrenal chromaffin cell grafts in PD patients. number of TH positive dopaminergic neurons and dopamine secretion, while norepinephrine and epinephrine production was reduced (Chung et al, 2009;Ehrhart-Bornstein et al, 2010;Vukicevic et al, 2012). Currently, our laboratory is assessing the viability of chromosphere grafts and its effects on behavior.…”