To evaluate the efficacy of autologous adipose-derived mesenchymal stem cell (ADMSC) therapy on pain, function and disease modification in knee osteoarthritis. Methods: 30 participants with symptomatic knee osteoarthritis were randomized into three groups. Two treatment groups received intra-articular ADMSC therapy consisting of either a single injection (100 × 10 6 ADMSCs) or two injections (100 × 10 6 ADMSCs at baseline and 6 months). The third group served as control and continued conservative management. Results: No serious adverse events were observed. Both treatment groups receiving ADMSCs showed clinically significant pain and functional improvement at completion of follow-up at 12 months. Radiological analysis using the Magnetic Resonance Imaging Osteoarthritis Knee Score indicated modification of disease progression. Conclusion: Autologous ADMSC therapy appears to be a safe and effective therapy for knee osteoarthritis and may have the potential to prevent disease progression.Trial registration number: ACTRN12614000814673
Osteoarthritis is a leading cause of pain and disability across the world. With an aging population its prevalence is likely to further increase. Current accepted medical treatment strategies are aimed at symptom control rather than disease modification. Surgical options including joint replacement are not without possible significant complications. A growing interest in the area of regenerative medicine, led by an improved understanding of the role of mesenchymal stem cells in tissue homeostasis and repair, has seen recent focused efforts to explore the potential of stem cell therapies in the active management of symptomatic osteoarthritis. Encouragingly, results of pre-clinical and clinical trials have provided initial evidence of efficacy and indicated safety in the therapeutic use of mesenchymal stem cell therapies for the treatment of knee osteoarthritis. This paper explores the pathogenesis of osteoarthritis and how mesenchymal stem cells may play a role in future management strategies of this disabling condition.
IntroductionThe management of intra-articular chondral defects in the knee remains a challenge. Inadequate healing in areas of weight bearing leads to impairment in load transmission and these defects predispose to later development of osteoarthritis. Surgical management of full thickness chondral defects include arthroscopic microfracture and when appropriate autologous chondrocyte implantation. This latter method however is technically challenging, and may not offer significant improvement over microfracture. Preclinical and limited clinical trials have indicated the capacity of mesenchymal stem cells to influence chondral repair. The aim of this paper is to describe the methodology of a pilot randomised controlled trial comparing arthroscopic microfracture alone for isolated knee chondral defects versus arthroscopic microfracture combined with postoperative autologous adipose derived mesenchymal stem cell injections.Methods and analysisA pilot single-centre randomised controlled trial is proposed. 40 participants aged 18–50 years, with isolated femoral condyle chondral defects and awaiting planned arthroscopic microfracture will be randomly allocated to a control group (receiving no additional treatment) or treatment group (receiving postoperative adipose derived mesenchymal stem cell treatment). Primary outcome measures will include MRI assessment of cartilage volume and defects and the Knee Injury and Osteoarthritis Outcome Score. Secondary outcomes will include further MRI assessment of bone marrow lesions, bone area and T2 cartilage mapping, a 0–10 Numerical Pain Rating Scale, a Global Impression of Change score and a treatment satisfaction scale. Adverse events and cointerventions will be recorded. Initial outcome follow-up for publication of results will be at 12 months. Further annual follow-up to assess long-term differences between the two group will occur.Ethics and disseminationThis trial has received prospective ethics approval through the Latrobe University Human Research Ethics Committee. Dissemination of outcome data is planned through both national and international conferences and formal publication in a peer-reviewed journal.Trial registration numberAustralia and New Zealand Clinical Trials Register (ANZCTR Trial ID: ACTRN12614000812695).
Tendinopathy is a common condition of both the athletic and general population and can be associated with significant pain and disability. The ability of mesenchymal stem cells (MSCs) to differentiate along a mesodermal cell lineage, including tenocytes, and secrete various bioactive regenerative and anti-inflammatory molecules has seen them considered as a future reparative therapy for tendinopathy. Preclinical trials with MSCs have shown promising positive functional and structural outcomes in several connective tissue related conditions. A 52-year-old male professional masters golfer presents with a clinical history of common extensor origin tendinopathy of the elbow. Subsequent formal ultrasound showed evidence of a large intrasubstance tear. The patient underwent intratendinous autologous adipose-derived MSC therapy in combination with autologous platelet-rich plasma. Following treatment, the patient reported progressive improvement as measured by the validated Numeric Pain Rating Scale and Patient-Rated Tennis Elbow Evaluation score. Repeat imaging showed successful regeneration of tendon-like tissue.
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