Placental-expanded, mesenchymal cells improve muscle function following hip arthroplasty

Winkler, T.; Perka, C.; von Roth, P.; Agres, A. N.; Plage, H.; Preininger, B.; Pumberger, M.; Geissler, S.; Lukasiewicz Hagai, E.; Ofir, R.; Pinzur, L.; Eyal, E.; Stoltenburg-Didinger, G.; Meisel, C.; Consentius, C.; Streitz, M.; Reinke, P.; Duda, G. N.; Volk, H.-D.

doi:10.1101/297739

bioRxiv · 10.1101/297739

Placental-expanded, mesenchymal cells improve muscle function following hip arthroplasty

Winkler, T.·Perka, C.·von Roth, P.·Agres, A. N.·Plage, H.·Preininger, B.·Pumberger, M.·Geissler, S.·Lukasiewicz Hagai, E.·Ofir, R.·Pinzur, L.·Eyal, E.·Stoltenburg-Didinger, G.·Meisel, C.·Consentius, C.·Streitz, M.·Reinke, P.·Duda, G. N.·Volk, H.-D.

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Abstract

BackgroundNo 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.\n\nMethodsOur pilot phase I/IIa study was prospective, randomized, double blind and placebo-controlled. Twenty patients undergoing hip arthroplasty via a direct lateral approach were injected with 3.0x108 or 1.5x108 PLX-PAD or a placebo into the gluteus medius muscle.\n\nResultsWe 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.\n\nConclusionAllogeneic 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.\n\nTrial RegistrationClinicalTrials.gov (number NCT01525667) and EudraCT (number 2011-003934-16)\n\nFundingThe study was funded by the Sponsor, Pluristem Therapeutics, the Israeli innovation authority and the German Federal Ministry of Education and Research.\n\nConflict of interestT. Winkler, C. Perka and G.N. Duda are members of a clinical advisory board of Pluristem Ltd for future indications. T. Winkler, C. Perka, G.N. Duda, P. von Roth filed a patent together with Pluristem Ltd. E. Lukasiewicz Hagai, R. Ofir, L. Pinzur and E. Eyal are current or former employees of Pluristem Ltd. T. Winkler, P. Reinke and H.-D. Volk received in the past consulting fees from Pluristem Ltd. but not for this project.

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Winkler, T., Perka, C., von Roth, P., Agres, A. N., Plage, H., Preininger, B., Pumberger, M., Geissler, S., Lukasiewicz Hagai, E., Ofir, R., Pinzur, L., Eyal, E., Stoltenburg-Didinger, G., Meisel, C., Consentius, C., Streitz, M., Reinke, P., Duda, G. N., Volk, H.-D.. 2018-04-16. Placental-expanded, mesenchymal cells improve muscle function following hip arthroplasty. https://doi.org/10.1101/297739

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