Reduced number and impaired function of circulating progenitor cells in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is associated with premature and accelerated atherosclerosis. Circulating progenitor cells (CPCs) are circulating bone-marrow derived cells that play an important role in the repair of vascular damage that underlies the development of atherosclerosis. The objective of this study was to determine the number and functionality of CPCs in patients with SLE. The study included 44 female SLE patients in an inactive stage of disease and 35 age-matched female controls. CPC numbers in the circulation were determined by FACS with monoclonals against CD14, CD34 and CD133. Peripheral blood-derived mononuclear cell (PBMNC) fractions were cultured in angiogenic medium. The endothelial-like phenotype was confirmed and the colony forming unit (CFU) capacity, migratory capacity and the potential to form clusters on Matrigel were determined. Expression of apoptosis inhibiting caspase 8L was analyzed in PBMNCs and CPCs by gene transcript and protein expression assays. The number of CD34–CD133 double-positive cells (P < 0.001) as well as the CFU capacity (P = 0.048) was reduced in SLE patients. Migratory activity on tumor necrosis factor-α tended to be reduced in patient CPCs (P = 0.08). Migration on vascular endothelial growth factor showed no significant differences, nor were differences observed in the potential to form clusters on Matrigel. The expression of caspase 8L was reduced at the transcriptional level (P = 0.049) and strongly increased at the protein level after culture (P = 0.003). We conclude that CPC numbers are reduced in SLE patients and functionality is partly impaired. We suggest these findings reflect increased susceptibility to apoptosis of CPCs from SLE patients

In vivo behavior of trimethylene carbonate and ε‐caprolactone‐based (co)polymer networks: Degradation and tissue response

The in vivo erosion behavior of crosslinked (co)polymers based on trimethylene carbonate (TMC) and epsilon-caprolactone (CL) was investigated. High molecular weight poly(trimethylene carbonate) (PTMC) homopolymer- and copolymer films were crosslinked by gamma irradiation. To adjust the in vivo erosion rate of the (co)polymer films, both the irradiation dose (25, 50, or 100 kGy) for PTMC and composition (100-70 mol % TMC) at a constant irradiation dose of 25 kGy were varied. After subcutaneous implantation of irradiated films in rats, their in vivo behavior was evaluated qualitatively and quantitatively. When the irradiation dose for PTMC was increased from 25 to 100 kGy, the erosion rate of nonextracted PTMC films (determined at day 5) decreased from 39.7 +/- 16.0 mu m day(-1) to 15.1 +/- 2.5 mu m day(-1), and the number of lymphocytes in the tissue surrounding the films decreased from 235 +/- 114 cells mm(-2) to 64 +/- 33 cells mm(-2). The number of macrophages and giant cells at the tissue-polymer interface also decreased with increasing irradiation dose. All (co)polymer films eroded completely within 28 days of implantation. Variation of the TMC content of gamma irradiated (co)polymer films did not affect the tissue response to the gamma irradiated (co)polymer films and their in vivo erosion behavior much

Migratory response of circulating progenitor cells (CPCs) to tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF)

<p><b>Copyright information:</b></p><p>Taken from "Reduced number and impaired function of circulating progenitor cells in patients with systemic lupus erythematosus"</p><p>http://arthritis-research.com/content/9/4/R84</p><p>Arthritis Research & Therapy 2007;9(4):R84-R84.</p><p>Published online 31 Aug 2007</p><p>PMCID:PMC2206388.</p><p></p> CPCs from ten patients and ten controls were cultured in angiogenic medium for 14 days, detached and placed in the upper chamber of a migration chamber. The lower chamber was filled with medium alone or with medium with either 50 ng/ml VEGF or 50 ng/ml TNF-α. Migration on VEGF and TNF-α was calculated as percentage of migration increase of CPCs compared to spontaneous migration on medium only. The line represents the mean

Number of CD14, CD34, and CD133 positive cells per ml of peripheral blood

<p><b>Copyright information:</b></p><p>Taken from "Reduced number and impaired function of circulating progenitor cells in patients with systemic lupus erythematosus"</p><p>http://arthritis-research.com/content/9/4/R84</p><p>Arthritis Research & Therapy 2007;9(4):R84-R84.</p><p>Published online 31 Aug 2007</p><p>PMCID:PMC2206388.</p><p></p> The number of peripheral blood derived mononuclear cells from 20 patients and 20 controls that stained single-positive for CD14, CD34 and CD133 and co-stained for CD34 and CD133 were quantified by fluorescence activated cell sorting and are depicted here as the amount of positively stained cells per milliliter of peripheral blood (the line represents the median; *< 0.05; **< 0.01; ***< 0.001)