Regenerative potential of human muscle stem cells in chronic inflammation
1 Department of Orthopaedics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
2 Institut de Myologie, Inserm U974, CNRS, Groupe hospitalier Pitié-Salpétrière, Paris, France
3 Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
4 Department of Human and Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
5 Department of Orthopaedics, Rijnland Hospital, Simon Smitweg 1, 2353 GA Leiderdorp, The Netherlands
6 Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
Arthritis Research & Therapy 2011, 13:R207 doi:10.1186/ar3540Published: 15 December 2011
Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle.
As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation.
After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group.
In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate.