Repair of Torn Avascular Meniscal Cartilage Using Undifferentiated Autologous Mesenchymal Stem Cells: From In Vitro Optimization to a First-in-Human Study

Michael Whitehouse, Nicholas Howells, Michael Parry, Eric Austin, Wael Kafienah, Kyla Brady, Allen Goodship, Jonathan Eldridge, Ashley Blom, Anthony Hollander

Research output: Contribution to journalArticle (Academic Journal)peer-review

32 Citations (Scopus)
342 Downloads (Pure)

Abstract

Meniscal cartilage tears are common and predispose to osteoarthritis. Most occur in the avascular portion of the meniscus where current repair techniques usually fail. We described previously the use of undifferentiated autologous mesenchymal stem cells (MSCs) seeded onto a collagen scaffold (MSC/collagen-scaffold) to integrate meniscal tissues in vitro. Our objective was to translate this method into a cell therapy for patients with torn meniscus, with the long-term goal of delaying or preventing the onset of osteoarthritis. After in vitro optimisation, we tested an ovine-MSC/collagen-scaffold in a sheep meniscal cartilage tear model with promising results after 13 weeks, although repair was not sustained over 6 months. We then conducted a single centre, prospective, open-label first-in-human safety study of patients with an avascular meniscal tear. Autologous MSCs were isolated from an iliac crest bone marrow biopsy, expanded and seeded into the collagen scaffold. The resulting human-MSC/collagen-scaffold implant was placed into the meniscal tear prior to repair with vertical mattress sutures and the patients were followed for 2 years. Five patients were treated and there was significant clinical improvement on repeated measures analysis. Three were asymptomatic at 24 months with no MRI evidence of recurrent tear and clinical improvement in knee function scores. Two required subsequent meniscectomy due to re-tear or non-healing of the meniscal tear at approximately 15 months after implantation. No other adverse events occurred. We conclude that undifferentiated MSCs could provide a safe way to augment avascular meniscal repair in some patients. Registration: EU Clinical Trials Register, 2010-024162- 22.
Original languageEnglish
Pages (from-to)1237-1248
Number of pages12
JournalStem Cells Translational Medicine
Volume6
Issue number4
Early online date15 Dec 2016
DOIs
Publication statusPublished - 1 Apr 2017

Structured keywords

  • Centre for Surgical Research

Keywords

  • Mesenchymal stem cells
  • Cell therapy
  • Meniscal cartilage
  • Tissue engineering

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