Randomized Controlled Trial

. 2024 Oct 21;83(11):1572-1583.

doi: 10.1136/ard-2024-225771.

Allogenic bone marrow-derived mesenchymal stromal cell-based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study)

Yves-Marie Pers^{1

2}, Robert Soler-Rich³, Gianluca Vadalà⁴, Rosanna Ferreira⁵, Claire Duflos⁶, Marie-Christine Picot⁷, Fanchon Herman⁸, Sylvie Broussous⁹, Ana Sánchez^{10

11}, David Noriega¹², Francisco Ardura¹², Mercedes Alberca Zaballos^{11

13}, Verónica García^{11

13}, Virginia Gordillo Cano^{10

11}, Margarita González-Vallinas^{11

13}, Vicenzo Denaro¹⁴, Fabrizio Russo¹⁴, Jérôme Guicheux¹⁵, Joan Vilanova¹⁶, Lluís Orozco³, Hans-Jörg Meisel¹⁷, Matias Alfonso¹⁸, Francois Rannou¹⁹, Yves Maugars^{15

20}, Francis Berenbaum²¹, Frank P Barry²², Karin Tarte²³, Pascale Louis-Plence², Guilherme Ferreira-Dos-Santos^{3

24}, Javier García-Sancho^{11

13}, Christian Jorgensen^{25

26}; RESPINE consortium

Collaborators, Affiliations

Collaborators

RESPINE consortium:
Yann Thouvenin, Catherine Cyteval, Michelle Moya, Sophie Grasset, Wendy Renier, Grégoire Mercier, Fanny Cardon, Perrine Robin, Aziza Seddiki, Alban Pouvreau, Mathilde Buisson, Céline Engrand, Felipe Prosper Cardoso, Esther Herrmann, Caroline Parlier Cuau, Xavier Alomar Serrallach, Antoine Feydy, Frédérique Toulgoat, Danièle Noël, Guillaum Costecalde, Phillipe Bourin, Carlo C Quattrocchi, Abby Binch, Christian Hohaus, Joelle Dulong, Amelie Michon, Jimena Bouzas, Louis Casteilla, Christian Ruckes, Regina Kucharski, Claudia Cicione, Giuseppina Di Giacomo, Giorgia Petrucci, Veronica Tilotta, Francesca Cannata, Luca Ambrosio, Massimiliano Carassiti, Cécile Boyer, Eric Bord, Kevin Buffenoir, Johann Clouet

Affiliations

¹ Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, CHRU Lapeyronie, Montpellier, France.
² INSERM U 1183, Institute for Regenerative Medicine and Biotherapy, Montpellier, France.
³ Centro Médico Teknon, Barcelona, Spain.
⁴ Department of Orthopaedic and Trauma Surgery, Università Campus Bio-Medico di Roma, Roma, Italy.
⁵ Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpelliera, France.
⁶ Clinical Research and Epidemiology Unit (Public Health Department), Montpellier, Languedoc-Roussillon, France.
⁷ Department of Medical Information, Clinical Research and Epidemiology Unit (Public Health Department), Montpellier, Languedoc-Roussillon, France.
⁸ Clinical Research and Epidemiology Unit (Public Health Department), Montpellier, France.
⁹ 7Research and Innovation Department, CHU Montpellier, University of Montpellier, Montpellier, France.
¹⁰ Unit of Excellence Institute of Biomedicine and Molecular Genetics of Valladolid (IBGM), Valladolid, Spain.
¹¹ Citospin SL, Valladolid, Spain.
¹² Orthopedic Surgery Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
¹³ Department of Biochemistry, Molecular Biology and Physiology, School of Medicine, Universidad de Valladolid, Valladolid, Spain.
¹⁴ Department of Orthopaedic and Trauma Surgery, Università Campus Bio-Medico di Roma, Roma, Lazio, Italy.
¹⁵ Regenerative Medicine and Skeleton, RMeS, Nantes Université, Oniris, INSERM, CHU Nantes, Nantes, France.
¹⁶ Centro Médico Teknon, Barcelona, Catalunya, Spain.
¹⁷ University Hospital Halle, Halle, Sachsen-Anhalt, Germany.
¹⁸ Orthopaedic Surgery and Traumatology Department, Clínica Universidad de Navarra, Pamplona, Spain.
¹⁹ Hôpital Cochin, Paris, Île-de-France, France.
²⁰ Service de Rhumatologie, Hôtel-Dieu, CHU Nantes, Nantes, France.
²¹ Rheumatology department, Hôpital Saint-Antoine, Paris, France.
²² Regenerative Medicine Institute, University of Galway Regenerative Medicine Institute, Galway, Ireland.
²³ Laboratoire SITI, Pôle Biologie, CHU Rennes, Rennes, Bretagne, France.
²⁴ Division of Pain Medicine, Department of Anesthesiology, Reanimation, and Pain Medicine, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.
²⁵ INSERM U 1183, Institute for Regenerative Medicine and Biotherapy, Montpellier, France christian.jorgensen@inserm.fr.
²⁶ Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Department of Rheumatology, CHU Montpellier, Montpellier, France.

PMID: 39393844
PMCID: PMC11503111
DOI: 10.1136/ard-2024-225771

Randomized Controlled Trial

Allogenic bone marrow-derived mesenchymal stromal cell-based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study)

Yves-Marie Pers et al. Ann Rheum Dis. 2024.

. 2024 Oct 21;83(11):1572-1583.

doi: 10.1136/ard-2024-225771.

Authors

Collaborators

RESPINE consortium:
Yann Thouvenin, Catherine Cyteval, Michelle Moya, Sophie Grasset, Wendy Renier, Grégoire Mercier, Fanny Cardon, Perrine Robin, Aziza Seddiki, Alban Pouvreau, Mathilde Buisson, Céline Engrand, Felipe Prosper Cardoso, Esther Herrmann, Caroline Parlier Cuau, Xavier Alomar Serrallach, Antoine Feydy, Frédérique Toulgoat, Danièle Noël, Guillaum Costecalde, Phillipe Bourin, Carlo C Quattrocchi, Abby Binch, Christian Hohaus, Joelle Dulong, Amelie Michon, Jimena Bouzas, Louis Casteilla, Christian Ruckes, Regina Kucharski, Claudia Cicione, Giuseppina Di Giacomo, Giorgia Petrucci, Veronica Tilotta, Francesca Cannata, Luca Ambrosio, Massimiliano Carassiti, Cécile Boyer, Eric Bord, Kevin Buffenoir, Johann Clouet

Affiliations

¹ Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, CHRU Lapeyronie, Montpellier, France.
² INSERM U 1183, Institute for Regenerative Medicine and Biotherapy, Montpellier, France.
³ Centro Médico Teknon, Barcelona, Spain.
⁴ Department of Orthopaedic and Trauma Surgery, Università Campus Bio-Medico di Roma, Roma, Italy.
⁵ Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpelliera, France.
⁶ Clinical Research and Epidemiology Unit (Public Health Department), Montpellier, Languedoc-Roussillon, France.
⁷ Department of Medical Information, Clinical Research and Epidemiology Unit (Public Health Department), Montpellier, Languedoc-Roussillon, France.
⁸ Clinical Research and Epidemiology Unit (Public Health Department), Montpellier, France.
⁹ 7Research and Innovation Department, CHU Montpellier, University of Montpellier, Montpellier, France.
¹⁰ Unit of Excellence Institute of Biomedicine and Molecular Genetics of Valladolid (IBGM), Valladolid, Spain.
¹¹ Citospin SL, Valladolid, Spain.
¹² Orthopedic Surgery Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
¹³ Department of Biochemistry, Molecular Biology and Physiology, School of Medicine, Universidad de Valladolid, Valladolid, Spain.
¹⁴ Department of Orthopaedic and Trauma Surgery, Università Campus Bio-Medico di Roma, Roma, Lazio, Italy.
¹⁵ Regenerative Medicine and Skeleton, RMeS, Nantes Université, Oniris, INSERM, CHU Nantes, Nantes, France.
¹⁶ Centro Médico Teknon, Barcelona, Catalunya, Spain.
¹⁷ University Hospital Halle, Halle, Sachsen-Anhalt, Germany.
¹⁸ Orthopaedic Surgery and Traumatology Department, Clínica Universidad de Navarra, Pamplona, Spain.
¹⁹ Hôpital Cochin, Paris, Île-de-France, France.
²⁰ Service de Rhumatologie, Hôtel-Dieu, CHU Nantes, Nantes, France.
²¹ Rheumatology department, Hôpital Saint-Antoine, Paris, France.
²² Regenerative Medicine Institute, University of Galway Regenerative Medicine Institute, Galway, Ireland.
²³ Laboratoire SITI, Pôle Biologie, CHU Rennes, Rennes, Bretagne, France.
²⁴ Division of Pain Medicine, Department of Anesthesiology, Reanimation, and Pain Medicine, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.
²⁵ INSERM U 1183, Institute for Regenerative Medicine and Biotherapy, Montpellier, France christian.jorgensen@inserm.fr.
²⁶ Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Department of Rheumatology, CHU Montpellier, Montpellier, France.

PMID: 39393844
PMCID: PMC11503111
DOI: 10.1136/ard-2024-225771

Abstract

Objectives: To assess the efficacy of a single intradiscal injection of allogeneic bone marrow mesenchymal stromal cells (BM-MSCs) versus a sham placebo in patients with chronic low back pain (LBP).

Methods: Participants were randomised in a prospective, double-blind, controlled study to receive either sham injection or intradiscal injection of 20 million allogeneic BM-MSC, between April 2018 and December 2022. The first co-primary endpoint was the rate of responders defined by improvement of the Visual Analogue Scale (VAS) for pain of at least 20% and 20 mm, or improvement of the Oswestry Disability Index (ODI) of 20% between baseline and month 12. The secondary structural co-primary endpoint was assessed by the disc fluid content measured by quantitative MRI T2, between baseline and month 12. Secondary endpoints included pain VAS, ODI, the Short Form (SF)-36 and the minimal clinically important difference in all timepoints (1, 3, 6, 12 and 24 months). We determined the immune response associated with allogeneic cell injection between baseline and 6 months. Serious adverse events (SAEs) were recorded.

Results: 114 patients were randomised (n=58, BM-MSC group; n=56, sham placebo group). At 12 months, the primary outcome was not reached (74% in the BM-MSC group vs 69% in the placebo group; p=0.77). The groups did not differ in all secondary outcomes. No SAE related to the intervention occurred.

Conclusions: While our study did not conclusively demonstrate the efficacy of allogeneic BM-MSCs for LBP, the procedure was safe. Long-term outcomes of MSC therapy for LBP are still being studied.

Trial registration number: EudraCT 2017-002092-25/ClinicalTrials.gov: NCT03737461.

Keywords: Biological Therapy; Low Back Pain; Orthopedic Procedures.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

**Figure 1. Flow chart of the RESPINE study. BM-MSC, bone marrow mesenchymal stromal cell.**

**Figure 2. Evolution of pain, disability and quality of life throughout the study. Dots: mean. Error bars: SD.**

See this image and copyright information in PMC

References

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1. Palazzo C, Ravaud JF, Papelard A, et al. The burden of musculoskeletal conditions. PLoS One. 2014;9:e90633. doi: 10.1371/journal.pone.0090633. - DOI - PMC - PubMed
1. Peng B-G. Pathophysiology, diagnosis, and treatment of discogenic low back pain. World J Orthop. 2013;4:42–52. doi: 10.5312/wjo.v4.i2.42. - DOI - PMC - PubMed
1. Taher F, Essig D, Lebl DR, et al. Lumbar degenerative disc disease: current and future concepts of diagnosis and management. Adv Orthop. 2012;2012:970752. doi: 10.1155/2012/970752. - DOI - PMC - PubMed
1. Knezevic NN, Candido KD, Vlaeyen JWS, et al. Low back pain. Lancet. 2021;398:78–92. doi: 10.1016/S0140-6736(21)00733-9. - DOI - PubMed

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Allogenic bone marrow-derived mesenchymal stromal cell-based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study)

Collaborators

Affiliations

Allogenic bone marrow-derived mesenchymal stromal cell-based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study)

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Associated data

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous