Abstract
SummaryObjectiveThis study investigated the effect of hUC-MSCs on osteoarthritis (OA) progression in a xenogeneic model.DesignMale, 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 and 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.ResultsPMM 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.ConclusionBeneficial 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.
Highlights
Osteoarthritis (OA) is the most common musculoskeletal disorder in our society but is seriously debilitating, impacting more on an individual's quality of life than cancer, diabetes or heart disease [1]
Beneficial change in a partial medial meniscectomy (PMM) joint was seen with only one hUC-MSC population, perhaps indicating that cell therapy is not appropriate for severely osteoarthritic joints
None of the implanted cells appeared to elicit an inflammatory response at the time-points studied
Summary
Osteoarthritis (OA) is the most common musculoskeletal disorder in our society but is seriously debilitating, impacting more on an individual's quality of life than cancer, diabetes or heart disease [1]. The most frequent treatment option for patients is arthroplasty at the end stage of the disease, replacing the degenerate joint with an inert prosthetic device, which has a finite lifespan. With an increasingly aged society, more arthroplasties are requiring revision and replacement year on year; these are more challenging, more expensive and less successful than the original surgery [2]. Autologous chondrocyte implantation (ACI) has been used for over two decades for treating more discrete chondral or osteochondral defects in the knee [3,4], which if left untreated often progress to end stage osteoarthritis [5].
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