Percutaneous administration of allogeneic bone-forming cells for the treatment of delayed unions of fractures: a pilot study

Stem Cell Research & Therapy

Wendy Sonnet¹  Guy Heynen¹  Richard Witvrouw²  Arndt Peter Schulz³  Lothar Seefried⁴  Bruno Vande Berg⁵  Marc Jayankura⁶  Olivier Delahaut⁷ 

[1] Bone Therapeutics S.A., Gosselies, Belgium;Department of Traumatology and Orthopaedics, Oost-Limburg Hospital, Schiepse Bos 2, Genk, Belgium;Klinik für Orthopädie und Unfallchirurgie, Universität zu Lübeck, Ratzeburger Allee 160, 23568, Lübeck, Germany;Labor für Biomechanik, BG Klinikum Hamburg, Bergedorfer Str. 10, 21033, Hamburg, Germany;Fraunhofer Research Institution for Individualized and Cell-Based Medical Engineering, Mönkhofer Weg 239 a, 23562, Lübeck, Germany;Orthopedic Department, University of Wuerzburg, Wuerzburg, Germany;Service de Radiologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium;Service d’Orthopédie – Traumatologie, Cliniques Universitaires de Bruxelles – Université Libre de Bruxelles, Hôpital Erasme, Route de Lennik 808, 1070, Brussels, Belgium;Service d’Orthopédie, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium;

关键词: Cell therapy;    Long bone;    Fracture;    Delayed union;    Treatment;    Allogeneic;    Bone marrow Mesenchymal stem cells;   

DOI  :  10.1186/s13287-021-02432-4

来源: Springer

【 摘 要 】

BackgroundOverall, 5–10% of fractures result in delayed unions or non-unions, causing major disabilities and a huge socioeconomic burden. 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.MethodsIn 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 months, received a percutaneous implantation of allogeneic bone-forming cells derived from bone marrow mesenchymal stem cells (ALLOB; Bone Therapeutics) into the fracture site (50 × 106 to 100 × 106 cells). Patients were monitored for adverse events and need for rescue surgery for 30 months. 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.ResultsDuring 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 months, but 2/21 (9.5%) patients had rescue surgery within 30 months post-treatment. At 6 months 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 months post-treatment, but no treatment-mediated allogeneic immune reactions were observed.ConclusionThis 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.Trial registrationNCT02020590. 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®) implantation in non-infected delayed-union fractures.

【 授权许可】

CC BY