Research Paper|Volume 10, Issue 11|pp 3173—3184

Effects of senescent secretory phenotype acquisition on human retinal pigment epithelial stem cells

Raffaella Lazzarini¹, Michele Nicolai², Vittorio Pirani², Cesare Mariotti², Roberto Di Primio¹

¹Department of Clinical and Molecular Sciences-Histology, Università Politecnica delle Marche, Ancona 60020, Italy
²Ophthalmology Clinic, Università Politecnica delle Marche, Ancona 60020, Italy

* * Equal contribution

Received: June 20, 2018Accepted: October 27, 2018Published: November 16, 2018

Copyright: © 2018 Lazzarini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Regenerative medicine approaches based on mesenchymal stem cells (MSCs) are being investigated to treat several aging-associated diseases, including age-related macular degeneration (AMD). Loss of retinal pigment epithelium (RPE) cells occurs early in AMD, and their transplant has the potential to slow disease progression.

The human RPE contains a subpopulation of cells - adult RPE stem cells (RPESCs) – that are capable of self-renewal and of differentiating into RPE cells in vitro. However, age-related MSC changes involve loss of function and acquisition of a senescence-associated secretory phenotype (SASP), which can contribute to the maintenance of a chronic state of low-grade inflammation in tissues and organs.

In a previous study we isolated, characterized, and differentiated RPESCs. Here, we induced replicative senescence in RPESCs and tested their acquisition of the senescence phenotype and the SASP as well as the differentiation ability of young and senescent RPESCs.

Senescent RPESCs showed a significantly reduced proliferation ability, high senescence-associated β-galactosidase activity, and SASP acquisition. RPE-specific genes were downregulated and p21 and p53 protein expression was upregulated.

These findings document the effects of senescence and SASP acquisition on RPESC differentiation ability and highlight the need for a greater understanding of their role in AMD pathogenesis.