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Since rescue surgery with autologous bone grafts can cause additional challenges, alternative treatment options have been developed to stimulate a deficient healing process. This study assessed the technical feasibility, safety and preliminary efficacy of local percutaneous implantation of allogeneic bone-forming cells in delayed unions of long bone fractures.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In this phase I\/IIA open-label pilot trial, 22 adult patients with non-infected delayed unions of long bone fractures, which failed to consolidate after 3 to 7\u2009months, received a percutaneous implantation of allogeneic bone-forming cells derived from bone marrow mesenchymal stem cells (ALLOB; Bone Therapeutics) into the fracture site (50 \u00d7 10<jats:sup>6<\/jats:sup> to 100 \u00d7 10<jats:sup>6<\/jats:sup> cells). Patients were monitored for adverse events and need for rescue surgery for 30\u2009months. Fracture healing was monitored by Tomographic Union Score (TUS) and modified Radiographic Union Score. The health status was evaluated using the Global Disease Evaluation (GDE) score and pain at palpation using a visual analogue scale. The presence of reactive anti-human leukocyte antigen (HLA) antibodies was evaluated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>During the 6-month follow-up, three serious treatment-emergent adverse events were reported in two patients, of which two were considered as possibly treatment-related. None of the 21 patients in the per-protocol efficacy population needed rescue surgery within 6\u2009months, but 2\/21 (9.5%) patients had rescue surgery within 30\u2009months post-treatment. At 6\u2009months post-treatment, an improvement of at least 2 points in TUS was reached in 76.2% of patients, the GDE score improved by a mean of 48%, and pain at palpation at the fracture site was reduced by an average of 61% compared to baseline. The proportion of blood samples containing donor-specific anti-HLA antibodies increased from 8\/22 (36.4%) before treatment to 13\/22 (59.1%) at 6\u2009months post-treatment, but no treatment-mediated allogeneic immune reactions were observed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This pilot study showed that the percutaneous implantation of allogeneic bone-forming cells was technically feasible and well tolerated in patients with delayed unions of long bone fractures. Preliminary efficacy evidence is supporting the further development of this treatment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02020590\">NCT02020590<\/jats:ext-link>. Registered on 25 December 2013. ALLOB-DU1, A pilot Phase I\/IIa, multicentre, open proof-of-concept study on the efficacy and safetyof allogeneic osteoblastic cells (ALLOB\u00ae) implantation in non-infected delayed-union fractures.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13287-021-02432-4","type":"journal-article","created":{"date-parts":[[2021,6,26]],"date-time":"2021-06-26T07:02:30Z","timestamp":1624690950000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Percutaneous administration of allogeneic bone-forming cells for the treatment of delayed unions of fractures: a pilot study"],"prefix":"10.1186","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5854-7071","authenticated-orcid":false,"given":"Marc","family":"Jayankura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt Peter","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Delahaut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Witvrouw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar","family":"Seefried","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Vande","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Heynen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Sonnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,26]]},"reference":[{"issue":"5","key":"2432_CR1","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.semcdb.2008.07.004","volume":"19","author":"A Schindeler","year":"2008","unstructured":"Schindeler A, McDonald MM, Bokko P, Little DG. 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The trial was conducted in agreement with the International Council on Harmonisation guidelines on Good Clinical Practice. The study protocol, all its amendments and the patient information sheet(s) were reviewed and approved by the appropriate Ethics Committees (CUB-ULB Erasme, Brussels, in Belgium and Universit\u00e4tsklinikum K\u00f6ln in Germany).This study was conducted in seven centres in Belgium and Germany (CUB-ULB H\u00f4pital Erasme, Belgium; CHU de Charleroi, Belgium; CHU St Pierre, Belgium; Ziekenhuis Oost-Limburg, Belgium; Klinikum rechts der Isar der TU M\u00fcnchen, Germany; Universit\u00e4tsklinikum Schleswig-Holstein, Campus L\u00fcbeck, Germany; Universit\u00e4t W\u00fcrzburg, Germany). A written, dated and signed informed consent was obtained from all patients or patients\u2019 legally acceptable representatives prior to any study procedure.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MJ, APS, OD, RW and LS declare having received fees for the study conduct from Bone Therapeutics to cover their principal investigator activities.BVB declares having received fees for consultancy and radiological reading from Bone Therapeutics.GH is an employee of Bone Therapeutics and owns shares in the company.WS is an employee of Bone Therapeutics.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"363"}}