Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

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

Tobias Winkler, Carsten Perka, Philipp von Roth, Alison N. Agres, Henning Plage, Bernd Preininger, Matthias Pumberger, Sven Geissler, Esther Lukasiewicz Hagai, Racheli Ofir, Lena Pinzur, Eli Eyal, Gisela Stoltenburg-Didinger, Christian Meisel, Christine Consentius, Mathias Streitz, Petra Reinke, Georg N. Duda, Hans-Dieter Volk
doi: https://doi.org/10.1101/297739
Tobias Winkler
1Center for Musculoskeletal Surgery and Julius Wolff Institute, Charité - Universitaetsmedizin Berlin, Germany
2Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carsten Perka
1Center for Musculoskeletal Surgery and Julius Wolff Institute, Charité - Universitaetsmedizin Berlin, Germany
3Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philipp von Roth
1Center for Musculoskeletal Surgery and Julius Wolff Institute, Charité - Universitaetsmedizin Berlin, Germany
3Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alison N. Agres
1Center for Musculoskeletal Surgery and Julius Wolff Institute, Charité - Universitaetsmedizin Berlin, Germany
2Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
3Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Henning Plage
1Center for Musculoskeletal Surgery and Julius Wolff Institute, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bernd Preininger
1Center for Musculoskeletal Surgery and Julius Wolff Institute, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthias Pumberger
1Center for Musculoskeletal Surgery and Julius Wolff Institute, Charité - Universitaetsmedizin Berlin, Germany
3Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sven Geissler
1Center for Musculoskeletal Surgery and Julius Wolff Institute, Charité - Universitaetsmedizin Berlin, Germany
2Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Esther Lukasiewicz Hagai
7Pluristem Ltd, Haifa, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Racheli Ofir
7Pluristem Ltd, Haifa, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lena Pinzur
7Pluristem Ltd, Haifa, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eli Eyal
7Pluristem Ltd, Haifa, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gisela Stoltenburg-Didinger
4Institute of Cell Biology and Neurobiology, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christian Meisel
6Institute for Medical Immunology, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christine Consentius
2Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
3Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mathias Streitz
2Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
6Institute for Medical Immunology, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Petra Reinke
2Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
5Clinic of Nephrology and Internal Intensive Care Medicine, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Georg N. Duda
1Center for Musculoskeletal Surgery and Julius Wolff Institute, Charité - Universitaetsmedizin Berlin, Germany
2Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
3Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: georg.duda@charite.de
Hans-Dieter Volk
2Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
3Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitaetsmedizin Berlin, Germany
6Institute for Medical Immunology, Charité - Universitaetsmedizin Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

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 placebo-controlled. Twenty patients undergoing hip arthroplasty via a direct lateral approach were injected with 3.0×108 or 1.5×108 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 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.

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.

Trial Registration ClinicalTrials.gov (number NCT01525667) and EudraCT (number 2011-003934-16)

Funding The study was funded by the Sponsor, Pluristem Therapeutics, the Israeli innovation authority and the German Federal Ministry of Education and Research.

Conflict of interest T. 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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted April 16, 2018.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Placental-expanded, mesenchymal cells improve muscle function following hip arthroplasty
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Placental-expanded, mesenchymal cells improve muscle function following hip arthroplasty
Tobias Winkler, Carsten Perka, Philipp von Roth, Alison N. Agres, Henning Plage, Bernd Preininger, Matthias Pumberger, Sven Geissler, Esther Lukasiewicz Hagai, Racheli Ofir, Lena Pinzur, Eli Eyal, Gisela Stoltenburg-Didinger, Christian Meisel, Christine Consentius, Mathias Streitz, Petra Reinke, Georg N. Duda, Hans-Dieter Volk
bioRxiv 297739; doi: https://doi.org/10.1101/297739
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Placental-expanded, mesenchymal cells improve muscle function following hip arthroplasty
Tobias Winkler, Carsten Perka, Philipp von Roth, Alison N. Agres, Henning Plage, Bernd Preininger, Matthias Pumberger, Sven Geissler, Esther Lukasiewicz Hagai, Racheli Ofir, Lena Pinzur, Eli Eyal, Gisela Stoltenburg-Didinger, Christian Meisel, Christine Consentius, Mathias Streitz, Petra Reinke, Georg N. Duda, Hans-Dieter Volk
bioRxiv 297739; doi: https://doi.org/10.1101/297739

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Clinical Trials
Subject Areas
All Articles
  • Animal Behavior and Cognition (4122)
  • Biochemistry (8831)
  • Bioengineering (6536)
  • Bioinformatics (23494)
  • Biophysics (11818)
  • Cancer Biology (9235)
  • Cell Biology (13351)
  • Clinical Trials (138)
  • Developmental Biology (7453)
  • Ecology (11432)
  • Epidemiology (2066)
  • Evolutionary Biology (15183)
  • Genetics (10458)
  • Genomics (14057)
  • Immunology (9193)
  • Microbiology (22222)
  • Molecular Biology (8833)
  • Neuroscience (47674)
  • Paleontology (352)
  • Pathology (1432)
  • Pharmacology and Toxicology (2493)
  • Physiology (3742)
  • Plant Biology (8099)
  • Scientific Communication and Education (1438)
  • Synthetic Biology (2226)
  • Systems Biology (6046)
  • Zoology (1258)