Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 333

Although research in the utilization of stem cell treatment for disease and injury to cartilage has increased over the past decade, the majority of the research to date has been conducted on animal models. Based upon results that showed significant improvements in repair of articular cartilage damage in animal models, there has been a recent expansion in the number of clinical trials in humans. In order to be deemed an effective method of treatment in humans, a method for the utilization of MSCs must at least be equal to the current treatment methods of cartilage repair, including debridement of the site, autologous chondrocyte implantation (ACI), and marrow-stimulating procedures. Recent clinical trials have attempted to identify methods for MSC treatment that produce the greatest regenerative effect by adjusting the originating source of the stem cells, method of delivery (surgery vs. injection), the type of scaffold utilized, and including additional cellular proteins and/or steroid hormones (growth and transcription factors) to aid in stem cell proliferation and guide differentiation to chondrocytes.

The majority of the completed clinical trials have utilized bone marrow–derived mesenchymal stem cells (BMSCs) for treatment. Surgical implantation has been the most common route of delivery of the BMSCs and has been conducted in eight clinical trials on conditions including osteoarthritic knees, patello-femoral cartilage deficits, and full-thickness knee defects. These trials have utilized scaffolds consisting of collagen gel, hydroxyapatite ceramic, and platelet fibrin glue in order to allow BMSC growth and differentiation to chondrocytes. Studies were analyzed either to identify cartilage regeneration, histologically or via clinical and subjective symptom improvement. Although only one study was compared via a control, all showed significant improvement over the duration of follow-up, which included periods from six months to two years.

One study that compared MSC to ACI treatment found similar improvement in both cases. However, it was noted that although ACI showed more effective treatment outcomes in patients under 45 years of age than in patients over 45, MSC did not show the same age bias. Three additional small studies have analyzed the effect of injection treatment of BMSCs for damaged knee cartilage. These studies also showed positive results in factors analyzed, including range of motion, pain, thickness of cartilage, and functional status.

Another group of clinical trials have utilized bone marrow concentrate (BMC) as a potential source of stem cells. Surgical treatment was the choice method of implantation for the majority of the BMC clinical trials. However, only one study utilized a control group method of treatment, ACI, in order to attempt to compare the effectiveness of treatment. This study utilized BMC with platelet-rich fibrin as a scaffold and hyaluronic acid, which is used commonly in attempts to treat osteoarthritis. Researchers found positive results in the regeneration of cartilage in both groups that were not significantly different from one another. Three additional surgical treatment clinical studies were performed and found positive results in clinical scores and growth of cartilage with BMC treatment.

A potential problem of overgrowth of cartilage, hypertrophy, was seen in a small number of the patients treated. A study assessing the effectiveness of injection treatment of BMC with debridement, a common therapy currently used to stimulate regrowth, was tested against a control group that underwent debridement alone. This study found shortened stay in the hospital and improvement of symptoms with the BMC injection.

A third group of clinical trials utilized adipose-derived mesenchymal stem cells (ADMSCs) as a source. The benefit of using ADMSCs is that they are very easily obtainable by clinicians, which makes it an attractive candidate for treatment. All three of the studies that used ADMSCs chose injection implantation as a route of delivery. Two of these studies utilized additional modifiers such as hyaluronic acid, the corticosteroid dexamethasone, and platelet-rich plasma in order to aid in the healing. All three of these studies had positive findings relating to cartilage thickness and clinical results.

Synovial-derived mesenchymal stem cells have been seen as a hopeful source of MSCs to stimulate cartilage regeneration. Synovial-derived mesenchymal cells have a greater chondrogenic than osteogenic potential. Therefore, the stem cells would have a greater likelihood of differentiating into cartilage rather than bone. This could increase the effect of treatment as well as potentially decrease negative side effects.

Although there were many positive findings signifying the effectiveness of MSCs on regeneration of cartilage, all of these early studies have low sample sizes and lack adequate randomization needed for definitive findings. Large randomized control studies will need to be conducted in order to prove the efficacy of MSCs in cartilage regeneration. In addition, more analysis will need to be conducted in order to determine benefits and risks of both surgical and injection treatments, as well as to determine the most appropriate methods of treatment.