15 research outputs found
Immunomodulatory placentalâexpanded, mesenchymal stromal cells improve muscle function following hip arthroplasty
Abstract Background No regenerative approach has thus far been shown to be effective in skeletal muscle injuries, despite their high frequency and associated functional deficits. We sought to address surgical traumaârelated muscle injuries using local intraoperative application of allogeneic placentaâderived, mesenchymalâlike adherent cells (PLXâPAD), using hip arthroplasty as a standardized injury model, because of the high regenerative and immunomodulatory potency of this cell type. Methods Our pilot phase I/IIa study was prospective, randomized, double blind, and placeboâcontrolled. Twenty patients undergoing hip arthroplasty via a direct lateral approach received an injection of 3.0 Ă 108 (300 M, n = 6) or 1.5 Ă 108 (150 M, n = 7) PLXâPAD or a placebo (n = 7) into the injured gluteus medius muscles. Results We did not observe any relevant PLXâPADârelated adverse events at the 2âyear followâup. Improved gluteus medius strength was noted as early as Week 6 in the treatmentâgroups. Surprisingly, until Week 26, the lowâdose group outperformed the highâdose group and reached significantly improved strength compared with placebo [150 M vs. placebo: P = 0.007 (baseline adjusted; 95% confidence interval 7.6, 43.9); preoperative baseline values mean ± SE: placebo: 24.4 ± 6.7 Nm, 150 M: 27.3 ± 5.6 Nm], mirrored by an increase in muscle volume [150 M vs. placebo: P = 0.004 (baseline adjusted; 95% confidence interval 6.0, 30.0); preoperative baseline values GM volume: placebo: 211.9 ± 15.3 cm3, 150 M: 237.4 ± 27.2 cm3]. Histology indicated accelerated healing after cell therapy. Biomarker studies revealed that lowâdose treatment reduced the surgeryârelated immunological stress reaction more than highâdose treatment (exemplarily: CD16+ NK cells: Day 1 P = 0.06 vs. placebo, P = 0.07 vs. 150 M; CD4+ Tâcells: Day 1 P = 0.04 vs. placebo, P = 0.08 vs. 150 M). Signs of lateâonset immune reactivity after highâdose treatment corresponded to reduced functional improvement. Conclusions Allogeneic PLXâPAD therapy improved strength and volume of injured skeletal muscle with a reasonable safety profile. Outcomes could be positively correlated with the modulation of early postoperative stressârelated immunological reactions
International, multicenter, randomized, controlled study comparing dynamically individualized versus standard treatment in patients with chronic hepatitis C
The aim of this study was to increase virologic response rates by individualized treatment according to the early virologic response