{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:47:38Z","timestamp":1779911258534,"version":"3.53.1"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T00:00:00Z","timestamp":1537315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"German Federal Ministry of Education and Research"},{"name":"Israeli Innovation Authority"},{"name":"Pluristem Therapeutics"},{"name":"European Commission. European Union's Horizon 2020","award":["779293"],"award-info":[{"award-number":["779293"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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\u2010related muscle injuries using local intraoperative application of allogeneic placenta\u2010derived, mesenchymal\u2010like adherent cells (PLX\u2010PAD), using hip arthroplasty as a standardized injury model, because of the high regenerative and immunomodulatory potency of this cell type.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Our pilot phase I\/IIa study was prospective, randomized, double blind, and placebo\u2010controlled. Twenty patients undergoing hip arthroplasty via a direct lateral approach received an injection of 3.0 \u00d7 10\n                      <jats:sup>8<\/jats:sup>\n                      (300 M,\n                      <jats:italic>n<\/jats:italic>\n                      = 6) or 1.5 \u00d7 10\n                      <jats:sup>8<\/jats:sup>\n                      (150\u00a0M,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a07) PLX\u2010PAD or a placebo (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a07) into the injured gluteus medius muscles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We did not observe any relevant PLX\u2010PAD\u2010related adverse events at the 2\u2010year follow\u2010up. Improved gluteus medius strength was noted as early as Week 6 in the treatment\u2010groups. Surprisingly, until Week 26, the low\u2010dose group outperformed the high\u2010dose group and reached significantly improved strength compared with placebo [150\u00a0M vs. placebo:\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.007 (baseline adjusted; 95% confidence interval 7.6, 43.9); preoperative baseline values mean \u00b1 SE: placebo: 24.4\u00a0\u00b1\u00a06.7\u00a0Nm, 150\u00a0M: 27.3\u00a0\u00b1\u00a05.6 Nm], mirrored by an increase in muscle volume [150\u00a0M vs. placebo:\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.004 (baseline adjusted; 95% confidence interval 6.0, 30.0); preoperative baseline values GM volume: placebo: 211.9\u00a0\u00b1\u00a015.3 cm\n                      <jats:sup>3<\/jats:sup>\n                      , 150\u00a0M: 237.4\u00a0\u00b1 27.2\u00a0cm\n                      <jats:sup>3<\/jats:sup>\n                      ]. Histology indicated accelerated healing after cell therapy. Biomarker studies revealed that low\u2010dose treatment reduced the surgery\u2010related immunological stress reaction more than high\u2010dose treatment (exemplarily: CD16+ NK cells: Day 1\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.06 vs. placebo,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.07 vs. 150\u00a0M; CD4+ T\u2010cells: Day 1\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.04 vs. placebo,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.08 vs. 150\u00a0M). Signs of late\u2010onset immune reactivity after high\u2010dose treatment corresponded to reduced functional improvement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Allogeneic PLX\u2010PAD 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\u2010related immunological reactions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12316","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T08:01:55Z","timestamp":1537344115000},"page":"880-897","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Immunomodulatory placental\u2010expanded, mesenchymal stromal cells improve muscle function following hip arthroplasty"],"prefix":"10.1002","volume":"9","author":[{"given":"Tobias","family":"Winkler","sequence":"first","affiliation":[{"name":"Center for Musculoskeletal Surgery and Julius Wolff Institute, Charit\u00e9\u2010Universitaetsmedizin Berlin  Berlin Germany"},{"name":"Berlin\u2010Brandenburg Center for Regenerative Therapies, Charit\u00e9\u2010Universitaetsmedizin Berlin  Berlin 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