Human adipose stem cell-conditioned medium increases survival of Friedreich's Ataxia cells submitted to oxidative stress

Abstract

Friedreich's ataxia (FA) is a multisystemic disorder characterized by progressive gait, ataxia, and cardiomyopathy. There are few treatments for this disease; thus, we analyzed in vitro the possible beneficial effect of adult stem cells in FA. To this end, human adipose stem cells from healthy individuals and periodontal ligament cells from FA patients were isolated and cultured. FA cells are especially vulnerable to oxidative stress; thus, they were submitted to this condition and cultured in adipose stem cell-conditioned medium. This resulted in increased cell survival and upregulation of oxidative-stress-related genes as well as frataxin, among other genes. A number of trophic factors were shown to be expressed by the adipose stem cells, especially brain-derived neurotrophic factor (BDNF), which was also identified in the conditioned medium. The culture of the ataxic cells under oxidative stress and in the presence of this trophic factor confirmed its protective effect. Thus, this work demonstrates that adipose stem cell-conditioned medium from healthy individuals is capable of changing the transcription levels of oxidative-stress-related genes in cells that are particularly susceptible to this condition, avoiding cellular degeneration. Also, this work shows how neurotrophic factors, particularly BDNF, are capable of increasing cell survival in response to oxidative stress, which occurs in many neurodegenerative diseases. © Copyright 2012, Mary Ann Liebert, Inc. 2012.This work has been financed by EUCOMMTOOLS, Science and Innovation Ministry (MICINN BFU-2008-00588, CONSOLIDER CSD2007-00023), Valencian government (PROMETEO/2009/028), Cell Therapy Network-Carlos III Health Institute (RD06/0010/0023), Alicia Koplowitz Foundation, Granada Foundation of Friedreich’s Ataxia, 5P- Syndrome Foundation, and Diógenes Foundation/Elche (CATEDRA ELA).Peer Reviewe