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Adipose derived mesenchymal stem cell therapy in the treatment of isolated knee chondral lesions: design of a randomised controlled pilot study comparing arthroscopic microfracture versus arthroscopic microfracture combined with postoperative mesenchymal stem cell injections

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Adipose derived mesenchymal stem cell therapy in the treatment of isolated knee chondral lesions: design of a randomised controlled pilot study comparing arthroscopic microfracture versus arthroscopic microfracture combined with postoperative mesenchymal stem cell injections

Julien Freitag 1, Jon Ford 2, Dan Bates 1, Richard Boyd 3, Andrew Hahne 2, Yuanyuan Wang 4, Flavia Cicuttini 4, Leesa Huguenin 1, Cameron Norsworthy 5, and Kiran Shah 6

1 Melbourne Stem Cell Centre, Melbourne, Victoria, Australia
2 Faculty of Health Sciences, La Trobe University, Melbourne, Victoria, Australia
3 Monash University, Melbourne, Victoria, Australia
4 Department of Epidemiology and Preventative Medicine, Monash Universty, Melbourne, Victoria, Australia
5 Department of Orthopaedic Surgeon, OrthoSport Victoria, Melbourne, Victoria, Australia
6 Magellan Stem Cells, Melbourne, Victoria, Australia


Introduction: The 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 analysis: A 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 dissemination: This 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.

Discussion: In this randomised pilot study we aim to compare the results of arthroscopic microfracture for isolated chondral defects (accepted surgical practice) versus microfracture with postoperative adipose derived MSC therapy. We hypothesise that postoperative intra-articular injections of adipose derived MSCs will result in better (hyaline-like) cartilage formation at the site of microfracture and therefore have greater efficacy in prevention of secondary osteoarthritis.

Primary outcome measures will be by both quantitative MRI analysis and the KOOS questionnaire. Secondary outcome measurements will include various validated pain and function questionnaires and further MRI analysis including novel cartilage quality assessment using T2 cartilage mapping techniques.

Patients will not be blinded. Both groups undergo routine microfracture treatment. The control group do not receive placebo injections postarthroscopic microfracture. While this may be perceived as a limitation and may effect some outcome measures, this will not affect primary outcome MRI assessment. Further, it was felt that intra-articular postoperative placebo injections presented an unacceptable risk.

Current research indicates that the use of peripheral blood mesenchymal stem cell therapy postarthroscopic microfracture may result in increased type II collagen deposition and development of hyaline-like cartilage. We aim to confirm this observation using adipose derived MSCs and further explore the appropriate protocol for postoperative MSC administration.

We hope to complete enrolment for the trial by mid-2016 with all 12-month follow-up data expected by mid-2017.

Trial registration number: Australia and New Zealand Clinical Trials Register (ANZCTR Trial ID: ACTRN12614000812695).

To read the full article, click here DOI: 10.1136/bmjopen-2015-009332

Related: Adipose Tissue, Cartilage Diseases, Knee Injuries, Osteoarthritis, Knee osteoarthritis, Mesenchymal Stem Cell Injections, Stem Cell Injections