Placental-expanded, mesenchymal 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 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 placebocontrolled. Twenty patients undergoing hip arthroplasty via a direct lateral approach were injected with 3.0×10 8 or 1.5×10 8 PLX-PAD or a placebo into the gluteus medius muscle. 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 treatmentgroups. 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 lowdose 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. 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.

Engineering Vascular Self‐Assembly by Controlled 3D‐Printed Cell Placement

“…[36,37] MSCs and fibroblasts have been used to induce regeneration in multiple constellations: human fibroblast allografts were used as treatment for diabetic foot ulcers or in restoring skin following severe burn injuries; [38,39] MSCs were used to induce bone defect healing or for ischemic heart diseases [39,40] or skeletal muscle regeneration. [41] However, fibroblasts are easier to be harvested and are known to play a critical role in wound healing and ECM formation, e.g., by depositing ECM surrounding nascent blood vessels, fibronectin, and collagen. [6,38,42] Due to the exhibited differences and the scarcity of studies with a direct comparison between MSCs and fibroblasts in respect to influencing endothelial cells in their vascular formation in 3D constructs in vitro, we included this comparison in our study.…”

Perinatal Cells: A Promising COVID-19 Therapy?

“…In addition, the large muscle tissue allows for multiple injection sites (Caplan et al, 2019;Hamidian Jahromi and Davies, 2019). IM delivery has been shown to be safe (reviewed in Caplan et al, 2019;Hamidian Jahromi and Davies, 2019) in several clinical studies (Winkler et al, 2018;Norgren et al, 2019) with placenta-derived mesenchymal-like cells [PLacental eXpanded (PLX)-PAD] and is now being tested in a double-blind, multicenter study to evaluate the efficacy of PLX-PAD for the treatment of COVID-19 (NCT04389450). PLX-PAD cells are adherent stromal cells isolated from the placenta of healthy women following a cesarean section.…”

Mesenchymal stromal cell and bone marrow concentrate therapies for musculoskeletal indications: a concise review of current literature

“…The high dose group displayed an initial superior increase in muscle force but did not reach a significant higher force compared to the placebo group at final measurement, again demonstrating that the dosing is a critical issue in cell based therapies. No safety concerns were noted during the study and follow-up [63].…”