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Clinical Trial
. 2020 Apr:51 Suppl 1:S63-S73.
doi: 10.1016/j.injury.2020.02.070. Epub 2020 Feb 26.

Early efficacy evaluation of mesenchymal stromal cells (MSC) combined to biomaterials to treat long bone non-unions

Enrique Gómez-Barrena  1 , Norma Padilla-Eguiluz  2 , Philippe Rosset  3 , Florian Gebhard  4 , Philippe Hernigou  5 , Nicola Baldini  6 , Helène Rouard  7 , Luc Sensebé  8 , Rosa-María Gonzalo-Daganzo  9 , Rosaria Giordano  10 , Eduardo García-Rey  2 , José Cordero-Ampuero  11 , Juan Carlos Rubio-Suárez  2 , Marta Dominguez García-Simón  2 , Julien Stanovici  3 , Christian Ehrnthaller  4 , Markus Huber-Lang  4 , Charles Henri Flouzat-Lachaniette  5 , Nathalie Chevallier  7 , Davide Maria Donati  6 , Benedetta Spazzoli  6 , Gabriela Ciapetti  6 , Sandrine Fleury  8 , Manuel-Nicolás Fernandez  9 , José-Rafael Cabrera  9 , Cristina Avendaño-Solá  9 , Tiziana Montemurro  10 , Carmen Panaitescu  12 , Elena Veronesi  13 , Markus Thomas Rojewski  14 , Ramin Lotfi  14 , Massimo Dominici  13 , Hubert Schrezenmeier  14 , Pierre Layrolle  15
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Free article
Clinical Trial

Early efficacy evaluation of mesenchymal stromal cells (MSC) combined to biomaterials to treat long bone non-unions

Enrique Gómez-Barrena et al. Injury. 2020 Apr.
Free article

Abstract

Background and study aim: Advanced therapy medicinal products (ATMP) frequently lack of clinical data on efficacy to substantiate a future clinical use. This study aims to evaluate the efficacy to heal long bone delayed unions and non-unions, as secondary objective of the EudraCT 2011-005441-13 clinical trial, through clinical and radiological bone consolidation at 3, 6 and 12 months of follow-up, with subgroup analysis of affected bone, gender, tobacco use, and time since the original fracture.

Patients and methods: Twenty-eight patients were recruited and surgically treated with autologous bone marrow derived mesenchymal stromal cells expanded under Good Manufacturing Practices, combined to bioceramics in the surgical room before implantation. Mean age was 39 ± 13 years, 57% were males, and mean Body Mass Index 27 ± 7. Thirteen (46%) were active smokers. There were 11 femoral, 4 humeral, and 13 tibial non-unions. Initial fracture occurred at a mean ± SD of 27.9 ± 31.2 months before recruitment. Efficacy results were expressed by clinical consolidation (no or mild pain if values under 30 in VAS scale), and by radiological consolidation with a REBORNE score over 11/16 points (value of or above 0.6875). Means were statistically compared and mixed models for repeated measurements estimated the mean and confidence intervals (95%) of the REBORNE Bone Healing scale. Clinical and radiological consolidation were analyzed in the subgroups with Spearman correlation tests (adjusted by Bonferroni).

Results: Clinical consolidation was earlier confirmed, while radiological consolidation at 3 months was 25.0% (7/28 cases), at 6 months 67.8% (19/28 cases), and at 12 months, 92.8% (26/28 cases including the drop-out extrapolation of two failures). Bone biopsies confirmed bone formation surrounding the bioceramic granules. All locations showed similar consolidation, although this was delayed in tibial non-unions. No significant gender difference was found in 12-month consolidation (95% confidence). Higher consolidation scale values were seen in non-smoking patients at 6 (p = 0.012, t-test) and 12 months (p = 0.011, t-test). Longer time elapsed after the initial fracture did not preclude the occurrence of consolidation.

Conclusion: Bone consolidation was efficaciously obtained with the studied expanded hBM-MSCs combined to biomaterials, by clinical and radiological evaluation, and confirmed by bone biopsies, with lower consolidation scores in smokers.

Keywords: Bioceramics; Clinical Consolidation; Efficacy; Long Bone; MSC; Non-union; Radiological Consolidation; Treatment.

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Conflict of interest statement

Declaration of Competing Interest The authors confirm that there are no known conflicts of interest associated with this publication and there has been no financial support for this work that could have influenced its outcome. The authors do not communicate any conflict of interest about this work and manuscript.

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