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

Autor: Allen E. Goodship, Eric Austin, Kyla Brady, Ashley W Blom, Michael Parry, Anthony P. Hollander, Michael R Whitehouse, Jonathan Eldridge, Wael Kafienah, N. R. Howells
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
medicine.medical_specialty
Cell- and Tissue-Based Therapy
Osteoarthritis
Meniscus (anatomy)
In Vitro Techniques
Menisci
Tibial

Cell therapy
03 medical and health sciences
0302 clinical medicine
Tissue engineering
Translational Research Articles and Reviews
Tissue Engineering and Regenerative Medicine
medicine
Animals
Humans
Cells
Cultured

030222 orthopedics
Wound Healing
Sheep
Tissue Engineering
Tissue Scaffolds
business.industry
Cartilage
Mesenchymal stem cell
Mesenchymal Stem Cells
Cell Biology
General Medicine
medicine.disease
Torn meniscus
Surgery
Tibial Meniscus Injuries
030104 developmental biology
medicine.anatomical_structure
Centre for Surgical Research
Mesenchymal stem cells
Female
Stem cell
Wound healing
business
Meniscal cartilage
Cartilage Diseases
Developmental Biology
Zdroj: Stem Cells Translational Medicine
Whitehouse, M, Howells, N, Parry, M, Austin, E, Kafienah, W, Brady, K, Goodship, A, Eldridge, J, Blom, A & Hollander, A 2017, ' Repair of Torn Avascular Meniscal Cartilage Using Undifferentiated Autologous Mesenchymal Stem Cells : From In Vitro Optimization to a First-in-Human Study ', Stem Cells Translational Medicine, vol. 6, no. 4, pp. 1237-1248 . https://doi.org/10.1002/sctm.16-0199
DOI: 10.1002/sctm.16-0199
Popis: Meniscal cartilage tears are common and predispose to osteoarthritis (OA). 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 OA. After in vitro optimization, 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 center, 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 magnetic resonance imaging evidence of recurrent tear and clinical improvement in knee function scores. Two required subsequent meniscectomy due to retear or nonhealing 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.
Databáze: OpenAIRE