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Page 2 of 12 Chen et al. Plast Aesthet Res 2020;7:49 I http://dx.doi.org/10.20517/2347-9264.2020.28

In addition, a BMSCs/collagen gel composite for cartilage repair clinical trial in Taiwan was conducted in 2008,
and results suggested that there was an improvement in IKDC and MRI score at 9-years of follow-up. It appears
that the use of MSCs for OA and cartilage defect treatment may be a promising method.

Keywords: Mesenchymal stem cell, osteoarthritis, cartilage defect, cartilage regeneration

INTRODUCTION
[1]
Cartilage offers high compressive force and covers the surfaces of synovial joints . Its main function is
[2]
to transmit and distribute loads and to further provide lubrication in the diarthrodial joints . Healthy
articular surfaces in humans demonstrate a hyaline cartilage morphology with thickness of about 2 to 4 mm.
Cartilage comprise of 65%-85% of water, 12%-24% of collagen, 3%-6% of glycosaminoglycans, and 16,000-
[3]
90,000 chondrocytes per microgram of wet tissue . The biomechanical properties of articular cartilage
[4]
are related to the composition and integrity of its extracellular matrix (ECM) . Cartilage may function
well throughout life, but damage to this tissue is prominent and has been described to afflict more than
21 million patients each year in the United States alone.

[5]
Osteoarthritis (OA) is one of the most common joint disorders related to cartilage . In the United States
alone, several millions of patients suffer from OA and treatment of this condition costs about 185.5 billion
[7]
[6]
dollars annually . OA pathology also ranks as the fourth leading cause of disability in Asia In addition,
OA has a 12% prevalence rate in patients more than 60 years of age, and this is forecasted to increase within
[8]
the next 10 years . It has also been reported that the incidence of OA has doubled in women, and tripled
[9]
in men, in recent years . Risk factors increasing its preponderance include that of age, gender, genetics,
[5]
nutrition and bone density which lead to greater susceptibility in OA .
Pro-inflammatory cytokines are also the critical mediators implicated in the pathophysiology of OA,
where they affect both quantity and quality of the cartilage ECM. Interleukin 1 beta (IL-1β), Tumor
necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) are the main pro-inflammatory cytokines related
to its pathogenesis. Elevated levels of IL-1β and TNF-α have been found in OA patient’s synovial fluid,
synovial membrane and subchondral bone. Several studies have also indicated that the presence of IL-1β
and TNF-α down-regulated type II collagen and aggrecan expression in chondrocyte, subsequently
stimulating the release of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3) and
matrix metalloproteinase-13 (MMP-13) [10,11] . IL-6 was also found to be elevated in OA patient’s synovial
[12]
fluid and sera , and it up-regulated the expression of MMP-1 and MMP-13 in combination with IL-1β
and oncostatin. These cytokines contribute to the pathogenesis of OA through down-regulation of anabolic
events and up-regulation of catabolic and inflammatory responses, resulting in structural damage to the
OA joint [13,14] .

Apart from OA, cartilage defects are another common source of joint disorders. Trauma, sports injuries,
biomechanical imbalance and genetic disease are common causes of cartilage defect. Patients suffering
from cartilage defects may experience pain and loss of articular function, with altered activities of daily
[15]
living. According to the international cartilage repair society ICRS grading system , cartilage defects can
be ranked from grade 1 (mildest) to grade 4 (most severe) which implies the most serious cartilage defect.
In grade 1, the cartilage lesions may be found within the superficial layers of the cartilage. Grade 2 lesions
occur when its depth extends down to less than 50% of the cartilage depth. When the lesion extends down
to more than 50% of the cartilage depth, this results in severely abnormal cartilage is classified as grade 3. In
the most severe defect grade 4, the lesion extends to subchondral bone and the underlying bony structures
are exposed. When the defect areas are large, pain evolves to become more severe, and limits patients’ daily
activities. Hence, treatment of OA and cartilage defects is critical to improve the quality of life.