The next generation of stem cell therapy: “From cartilage explants to arthritic patients”
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1
ANACURA group, Head R&D Global Stem cell Technology, Belgium
ABSTRACT
Background - In horses, 60% of lameness is correlated with osteoarthritis, which is considered a major economic loss for this industry. Because of promising results in several human and equine clinical trials during the past few years, the clinical use of regenerative therapies for the treatment of osteoarthritis is becoming increasingly relevant.
Materials & Methods - Peripheral blood (PB)-derived mesenchymal stem cells (MSCs) were isolated and characterized from three donor horses. Chondrogenic induction was performed and MSC markers and changes in mRNA and protein expression were analysed at early and late time points after isolation. In a subsequent organ culture study, a total of 180 stifle cartilage explants of six horses were included and standardized lesions were created. Uninduced and chondrogenic induced MSCs were used for the treatment of these lesions in 2 different doses and evaluated at 3 time points (day 1, 5 and 14). Lesions, cartilage regeneration and cell integration were blindly scored. Finally, uninduced MSCs were compared with chondrogenic induced MSCs for the treatment of osteoarthritis in 165 horses. Return to work was evaluated at 6 and 18 weeks after treatment.
Results - Isolated cells possessed all the properties to be characterized as MSCs. Cartilage genes (p = 0.0182 and p = 0.0351) demonstrated a significantly increased expression after chondrogenic induction and CD29, CD44, CD90, CD45, MHC II and a monocyte/macrophage marker remained constant over time and after induction. Adherent MSCs could be observed on the surface in 92.6% of the unloaded explants and in 40.7% cleft filling was present. Significantly more cartilage explants demonstrated cleft filling (p = 0.0022) and adhered MSCs (p = 0.0161) in the low dose group. Clump formation occurred in 39% of the uninduced MSC treated cartilage explants and detached before day 14, whereas no clumps were present in the chondrogenic induced MSC treated groups (p = 0.0156) demonstrating a more homogenous adhesion and integration on the cartilage. At 6 weeks after treatment with uninduced MSCs, 45% of the patients returned to work, whereas 60% of the horses treated with chondrogenic induced MSCs did so. The number of patients returning to work increased up to 18 weeks with 78% in the uninduced MSC-treated group and 86% in the chondrogenic induced MSC-treated group. With the odds ratio of 1.47 for short-term and 1.24 for long-term, higher average scores could be demonstrated using chondrogenic induced MSCs as compared to uninduced MSCs for all three lower limb joints.
Conclusion - Our results indicate that chondrogenic induction was successful and generated better results in explant cultures as well as in patients with naturally occurring osteoarthritis.
AUTHOR BIOGRAPHY
Jan H. Spaas, graduated as a Master in Veterinary Medicine from the Faculty of Veterinary Medicine, Ghent University (Belgium) and won the price for young authors of the Flemish Veterinary Journal in 2010. He completed his PhD in Veterinary Science about stem cell isolation and characterization at the Department of Comparative Physiology and Biometrics of the same Veterinary Faculty. In 2012, he became the laboratory director of Global Stem cell Technology (GST) and in 2015 he was appointed head R&D of the stem cell platform within the ANACURA group located in Evergem, Belgium.
He has published over 20 internationally peer-reviewed scientific publications and is inventor of 6 patents concerning stem cell cultivation techniques in mammals. From 2013, he became part of the International Society for Cellular Therapy (ISCT) and the European Society of Gene and Cell Therapy (ESGCT). He is industrial promotor of PhD and master students who actively participate in the company’s research program. In 2015, he was appointed Associate Editor for the Veterinary Regenerative Medicine section of Frontiers in Veterinary Science.
Acknowledgements
This study was supported by a grant (number 130543) to JHS from the agency for innovation by science and technology Flanders (IWT Vlaanderen). Furthermore, the authors would like to acknowledge GST and the ANACURA group with the sources of private funding, which have provided the basis for this study.
Keywords:
Cartilage,
Stem Cells,
Veterinary,
Equine,
Arthrosis
Conference:
First and Second Conference on Current Veterinary Practices, Meldert-Lummen and Evergem, Belgium, 5 Mar - 26 Mar, 2016.
Presentation Type:
Oral Presentation
Topic:
Current Veterinary Practices
Citation:
Spaas
JH
(2016). The next generation of stem cell therapy: “From cartilage explants to arthritic patients”.
Front. Vet. Sci.
Conference Abstract:
First and Second Conference on Current Veterinary Practices.
doi: 10.3389/conf.FVETS.2016.01.00003
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Received:
27 Jan 2016;
Published Online:
29 Jan 2016.
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Correspondence:
DVM, PhD. Jan H Spaas, ANACURA group, Head R&D Global Stem cell Technology, Evergem, 9940, Belgium, jan.spaas@anacura.com