Perry, J, McCarthy, HS ORCID: https://orcid.org/0000-0001-9534-7565, Bou-Gharios, G, Hof, RVT, Milner, PI, Mennan, C ORCID: https://orcid.org/0000-0001-9532-753X and Roberts, S ORCID: https://orcid.org/0000-0003-1835-327X (2020) Injected human umbilical cord-derived mesenchymal stromal cells do not appear to elicit an inflammatory response in a murine model of osteoarthritis. Osteoarthritis and Cartilage Open. 100044 - 100044.

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Abstract

Objective This study investigated the effect of hUC-MSCs on osteoarthritis (OA) progression in a xenogeneic model. Design Male, 10 week-old C57Bl/6 mice underwent sham surgery (n=15) or partial medial meniscectomy (PMM;n=76). 5x105 hUC-MSCs (from 3 donors: D1,D2,D3) were phenotyped via RT-qPCR and immunoprofiling their response to inflammatory stimuli. They were injected into the mouse joints 3 and 6 weeks post-surgery, harvesting joints at 8 and 12 weeks post-surgery, respectively. A no cell ‘control’ group was also used (n=29). All knee joints were assessed via micro-computed tomography (μCT) and histology and 10 plasma markers were analysed at 12 weeks. Results PMM resulted in cartilage loss and osteophyte formation resembling human OA at both time-points. Injection of one donor’s hUC-MSCs into the joint significantly reduced the loss of joint space at 12 weeks post-operatively compared with the PMM control. This ‘effective’ population of MSCs up-regulated the genes, IDO and TSG6, when stimulated with inflammatory cytokines, more than those from the other two donors. No evidence of an inflammatory response to the injected cells in any animals, either histologically or with plasma biomarkers, arose. Conclusion Beneficial change in a PMM joint was seen with only one hUC-MSC population, perhaps indicating that cell therapy is not appropriate for severely osteoarthritic joints. However, none of the implanted cells appeared to elicit an inflammatory response at the time-points studied. The variability of UC donors suggests some populations may be more therapeutic than others and donor characterisation is essential in developing allogeneic cell therapies.

Item Type: Article
Additional Information: The final manuscript and all relevant information can be found at; https://www.sciencedirect.com/science/article/pii/S2665913120300285?via%3Dihub
Uncontrolled Keywords: Umbilical cord, mesenchymal, inflammatory, osteoarthritis.
Subjects: Q Science > Q Science (General)
Q Science > QM Human anatomy
R Medicine > R Medicine (General)
R Medicine > RS Pharmacy and materia medica
R Medicine > RZ Other systems of medicine
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Depositing User: Symplectic
Date Deposited: 24 Feb 2020 15:33
Last Modified: 18 Sep 2020 12:49
URI: https://eprints.keele.ac.uk/id/eprint/7681

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