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Latest Discoveries in Treatment of Damaged Articular Cartilage
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In human organism there are three types of cartilage (articular or hyaline cartilage, fibrocartilage and elastic cartilage). Articular cartilage (AC) has the main focus in this article. Hyaline or articular cartilage is white, avascular, smooth tissue which lies on the ends of the bones. It has very smooth surface and provides very low percent of friction. The hydrophilic property of this cartilage provides cushion needed for shock absorbency. Because of avascularity, this tissue has no ability of self- renewal. Another property of this tissue is low cell turnover and low cellularity as well.

Chondrocytes are the most dominant cell type in AC. They present 95 percent of the cell population. Chondrocytes also present the main resource of the self- renewal. However, they slowly replicate themselves, even when tissue is damaged. Scientist and clinicians have tried to support chondrocytes division through many tests, because even a small cartilage injury can lead to severe osteoarthritis.

Current treatments

Many treatments are tested, but only two tests have shown best results. These test are microfracture and autologous chondrocyte implantation (ACI). These two treatments of cartilage are not perfect solution because these treatments give fibrocartilage instead of hyaline cartilage. The main obstacle with this fibrocartilage treatments is lack of quality and usually patients have further operations and treatments. Stem cells are ideal for regeneration and repairing damaged cartilage tissue as long as they can fill the defect with cells. These cells have to be able to differentiate later. Embryonic stem cells (ESCs) are possible solution, because they can differentiate in many different cell types. These embryonic stem cells can have successful differentiation in presence of bone morphogenic protein 2 and 4 (BMP2 and BMP4). Also, when these cells are exposed to transforming growth factor B3 there is an increase of glycosaminoglycan and collagen amount 14 days later. Another promising type of cells is adult mesenchymal stem cell (MSC). MSCs are very good alternative in articular cartilage restoring. They adapt very good because of their plasticity and multilineage potential. Another benefit of MSCs usage is their various location. These cells can be isolated from adipose tissue, muscles and bone marrow. Likewise, MSCs are less tumorigenic cells than ESCs.

Specifications of various adult mesenchymal stem cells

Stem cells gathered from bone marrow, adipose tissue, muscle, synovial membrane and peiosteum are several types of adult mesenchymal stem cells. Of course, these cell types are not clonal populations and they are heterogeneous. Usually fetal bovine serum is widely added to culture medium for culture expansion. However, zoonotic infection and immune reactions are not excluded in these method.

Stem cell from bone marrow (BMMSC) was discovered in past and it was sensational discovery because scientist have found out cell which can divide and differentiate in osteoblasts, chondrocytes and adipocytes. This type of stem cells is most studied to induce chondrogenesis in tissue cultures. The most responsible factors are TGF-β family. TGF-β1, TGF-β2 and TGF-β3 and members of BMP family like BMP-2, BMP-6 and BMP-7 are the most promising factors in chonrogenesis induction. These factors in cooperation have shown that they can increase collagen II expression more than single growth factor. Stem cells from adipose tissue (ATMSC) has inferior chondrogenic potential in comparison with stem cells from bone marrow. These stem cells are not producing satisfying results when treated with both growth factors separately or growth factors in synergism. Despite their preferences, scientists are interested in them, because they can be easily obtained from fat tissue in comparison with painful obtaining of BMMSC.

Stem cells from muscle tissue (MDSCs) have controversial chondrogenic potential in comparison with stem cells harvested from bone marrow. However, muscles stem cells have shown different chondrogenic potential in traumatized muscle and in normal muscle. MDSCs in traumatized muscle has bigger chondrogeniic potential than MDSCs from normal muscle.

Periosteum stem cell (PMSC) is not so promising method, but it exists as an option, and the last are stem cells from synovial membrane. Synovial membrane have two types of cells, but only fibroblast like cells are used as stem cells. They have similar chondrogenic potential as BMMSC, but they are much more easily obtained from the tissue.

Newest method of treatment with peripheral blood stem cells

Cartilage defects are very problematic in orthopedics, because even a tiny cartilage lesion can lead into a deliberating osteoarthritis. The new method is really based on one of the oldest known methods. This method is microfracture. This method is just a little bit changed, but it appears to be maybe the best way of treatment. After this microfracture, patient received intra- articularly an injection of 8 ml of harvested autologous peripheral blood progenitor cells (PBPCs) and 2 ml of hyaluronic acid. Five more injections were given on a weekly basis, and later, arthroscopy confirmed existence of true hyaline. This technique is not so complicated, but recovery is very long, up to two years until patient is fully recovered even for sports activities. However, this research is indicated in treatment of localized cartilage fractures only, thus it cannot be used in treatment of widespread arthritis.

Limitations in cartilage stem cell renewal therapy

Chondrogenesis with different stem cells has been investigated for many years in past. Despite, there are questions and limitations in these therapies. For example, tissue specific mesenchymal stem cells are well known to scientists, but their growth factor response is different. Also, mesenchymal stem cells harvested from same the tissue have different properties in differentiation and proliferation. One of the big things for future treatments could be sorting the MSCs by their surface markers. On the other side, there are doubts connected with embryonic stem cells. Despite their excellent dividing ability, their oncogenic potential is one of the biggest worries between scientists. In conclusion, optimization of morphogens like BMPs and growth factors is key of success in treatment of articular cartilage regeneration with stem cells.
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