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Immunomodulatory placental-expanded, 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 trauma-related muscle injuries using local intraoperative application of allogeneic placenta-derived, mesenchymal-like adherent cells (PLX-PAD), 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 placebo-controlled. Twenty patients undergoing hip arthroplasty via a direct lateral approach received an injection of 3.0 × 108 (300 M, n = 6) or 1.5 × 108 (150 M, n = 7) PLX-PAD or a placebo (n = 7) into the injured gluteus medius muscles. RESULTS:We did not observe any relevant PLX-PAD-related adverse events at the 2-year follow-up. Improved gluteus medius strength was noted as early as Week 6 in the treatment-groups. Surprisingly, until Week 26, the low-dose group outperformed the high-dose 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 low-dose treatment reduced the surgery-related immunological stress reaction more than high-dose treatment (exemplarily: CD16+ NK cells: Day 1 P = 0.06 vs. placebo, P = 0.07 vs. 150 M; CD4+ T-cells: Day 1 P = 0.04 vs. placebo, P = 0.08 vs. 150 M). Signs of late-onset immune reactivity after high-dose treatment corresponded to reduced functional improvement. CONCLUSIONS:Allogeneic PLX-PAD 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 stress-related immunological reactions.

SUBMITTER: Winkler T

PROVIDER: S-EPMC6204595 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Immunomodulatory placental-expanded, mesenchymal stromal cells improve muscle function following hip arthroplasty.

Winkler Tobias T Perka Carsten C von Roth Philipp P Agres Alison N AN Plage Henning H Preininger Bernd B Pumberger Matthias M Geissler Sven S Hagai Esther Lukasiewicz EL Ofir Racheli R Pinzur Lena L Eyal Eli E Stoltenburg-Didinger Gisela G Meisel Christian C Consentius Christine C Streitz Mathias M Reinke Petra P Duda Georg N GN Volk Hans-Dieter HD

Journal of cachexia, sarcopenia and muscle 20180919 5

<h4>Background</h4>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 trauma-related muscle injuries using local intraoperative application of allogeneic placenta-derived, mesenchymal-like adherent cells (PLX-PAD), using hip arthroplasty as a standardized injury model, because of the high regenerative and immunomodulatory potency of this cell type.<h4>Methods< ...[more]

PMID: 30230266

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Dataset Information

Immunomodulatory placental-expanded, mesenchymal stromal cells improve muscle function following hip arthroplasty.

Publications

Immunomodulatory placental-expanded, mesenchymal stromal cells improve muscle function following hip arthroplasty.

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