No regenerative approach has thus far been shown to be effective in skeletal muscle injuries, despite high frequency and associated functional deficits. We sought to address surgical trauma related muscle injuries using local intraoperative application of allogeneic placental-expanded, mesenchymal-like adherent cells (PLX-PAD), using hip arthroplasty as a standardized injury model, because of their high regenerative and immunomodulatory potency. 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 3.0Ã—108, 1.5Ã—108 PLX-PAD, or a placebo into their gluteus medius muscle. 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 outperformed the high-dose group and reached significantly improved strength compared to placebo, mirrored by an increase in muscle volume. 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. Signs of late-onset immune reactivity after high-dose treatment corresponded to reduced functional improvement. In conclusion 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.
charite, inst.med.immunology and bcrt
bcrt/dept. orthopedics, charite university medicine
dept. orthopedics/bsrt, charite university medicine
bcrt/dept. nephrology, charite university medicine
bcrt/jwi, charite university medicine