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

被引:209
作者
de Windt, Tommy S. [1 ]
Vonk, Lucienne A. [1 ]
Slaper-Cortenbach, Ineke C. M. [2 ]
van den Broek, Marcel P. H. [2 ]
Nizak, Razmara [1 ]
van Rijen, Mattie H. P. [1 ]
de Weger, Roel A. [3 ]
Dhert, Wouter J. A. [4 ]
Saris, Daniel B. F. [1 ,5 ]
机构
[1] Univ Med Ctr Utrecht, Dept Orthopaed, Heidelberglaan 100,POB G05-228, NL-3584 CX Utrecht, Netherlands
[2] Univ Med Ctr Utrecht, Dept Clin Pharm, Cell Therapy Facil, Utrecht, Netherlands
[3] Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands
[4] Univ Utrecht, Fac Vet Med, Utrecht, Netherlands
[5] Univ Twente, MIRA Inst Biomed Technol & Tech Med, Enschede, Netherlands
关键词
Bone marrow stromal cells; Cellular therapy; Clinical translation; Tissue regeneration; First in man; chondrons; STROMAL CELLS; TRANSPLANTATION; IMPLANTATION; DEFECTS; KNEE; SITE; DIFFERENTIATION; MICROFRACTURE; THERAPY; QUALITY;
D O I
10.1002/stem.2475
中图分类号
Q813 [细胞工程];
学科分类号
100113 [医学细胞生物学];
摘要
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.
引用
收藏
页码:256 / 264
页数:9
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