Details

Autor(en) / Beteiligte

• de Windt, Tommy S.
• Vonk, Lucienne A.
• Slaper‐Cortenbach, Ineke C. M.
• van den Broek, Marcel P. H.
• Nizak, Razmara
• van Rijen, Mattie H. P.
• de Weger, Roel A.
• Dhert, Wouter J. A.
• Saris, Daniel B. F.

Titel

Allogeneic Mesenchymal Stem Cells Stimulate Cartilage Regeneration and Are Safe for Single‐Stage Cartilage Repair in Humans upon Mixture with Recycled Autologous Chondrons

Ist Teil von

• Stem cells (Dayton, Ohio), 2017-01, Vol.35 (1), p.256-264

Ort / Verlag

United States: Oxford University Press

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Traditionally, mesenchymal stem cells (MSCs) isolated from adult bone marrow were described as being capable of differentiating to various lineages including cartilage. Despite increasing interest in these MSCs, concerns regarding their safety, in vivo behavior and clinical effectiveness have restrained their clinical application. We hypothesized that MSCs have trophic effects that stimulate recycled chondrons (chondrocytes with their native pericellular matrix) to regenerate cartilage. Searching for a proof of principle, this phase I (first‐in‐man) clinical trial applied allogeneic MSCs mixed with either 10% or 20% recycled autologous cartilage‐derived cells (chondrons) for treatment of cartilage defects in the knee in symptomatic cartilage defect patients. This unique first in man series demonstrated no treatment‐related adverse events up to one year postoperatively. At 12 months, all patients showed statistically significant improvement in clinical outcome compared to baseline. Magnetic resonance imaging and second‐look arthroscopies showed completely filled defects with regenerative cartilage tissue. Histological analysis on biopsies of the grafts indicated hyaline‐like regeneration with a high concentration of proteoglycans and type II collagen. Short tandem repeat analysis showed the regenerative tissue only contained patient‐own DNA. These findings support the novel insight that the use of allogeneic MSCs is safe and opens opportunities for other applications. Stem cell‐induced paracrine mechanisms may play an important role in the chondrogenesis and successful tissue regeneration found. Stem Cells 2017;35:256–264 Overview of the IMPACT therapy. During a mini‐arthrotomy cartilage is acquired form the debrided rim of the treated cartilage (a). The previously deemed waste cartilage is minced into small pieces of approximately 1 × 1 × 1 mm and transferred to a tube containing the digestion medium (b). During 40 minutes the cubical cartilage pieces are digested, releasing the chondrons (c). After washing the chondrons they are combined with the human allogeneic MSCs (d). The cell product containing the defect derived autologous chondrons and allogeneic MSCs is resuspended in the fibrin glue (e). The surgeon will apply the cell loaded fibrin glue to the debrided isolated cartilage defect (f). See http://youtu.be/CbZQ18Bvvtw for a video demonstration. Patients were followed for 18 months after treatment and were subjected to a rehabilitation program. No treatment‐related adverse events were found and all patients showed statistically significant clinical improvement.