Page 333 - Read Online

Page 4 of 14 Velasquillo et al. Plast Aesthet Res 2020;7:31 I http://dx.doi.org/10.20517/2347-9264.2020.30

Nowadays, treatment towards OA is oriented towards minimizing pain, optimizing function, and
modifying the process of joint damage. Pain control, as mentioned earlier, is what guides the physician’s
decision into which treatment to use. Analgesics and anti-inflammatory medications are the mainstay
[18]
treatment, accompanied by lifestyle modifications such as weight loss and physical therapy/activity . Since
no medication has been shown to stop the process of OA, measures have been taken to prevent it. Focal
cartilage lesions, if left untreated, tend to quickly progress into osteoarthritis.

A retrospective study performed in the National Institute of Rehabilitation in Mexico reported that 61%
of the patients undergoing arthroscopic surgery had focal chondral lesions in the knee, with 74% of
[19]
these being grade III-IV ICRS/Outerbridge . Cartilage reparation techniques, such as microfractures,
autologous chondrocyte implantation, and mosaicplasty have shown to delay the appearance of OA, as
well as the need for total joint replacement after chondral injuries in young adults [20-23] . Some biological
[24]
therapies have been researched, including drugs that promote chondrogenesis and osteogenesis , matrix
[25]
degradation inhibitors, apoptosis inhibitors, and anti-inflammatory cytokines ; however, none of them
[26]
have demonstrated sufficient symptom improvement to be included in the standard of care .
Mesenchymal stem cells have turned into the most explored therapeutic drug in cell-based OA treatment
[27]
due to their ability to differentiate to chondrocytes and their immunomodulatory properties . Furthermore,
they have been used in different ways to try and modify the course of the disease.

MSC seeded on scaffolds
Cartilage implants: by taking advantage of the differentiation capacity of MSC to chondrocytes, MSC
have been similarly used for cartilage lesion repair as matrix-assisted autologous chondrocyte implants.
Previous studies using chondrocytes seeded on collagen or polyglycolic-acid matrixes have shown good
mid- to long-term clinical and magnetic resonance imaging (MRI) outcomes, as well as the ability to delay
degenerative changes in the knee [28-31] .

A few years ago, the United States Food and Drug Administration approved MACI, a porcine collagen
[32]
membrane seeded with autologous chondrocytes, for the treatment of focal chondral lesions in the knee .
[33]
Okano et al. came up with the “cell sheet technology” consisting of multiple cell layers placed on top
of another (instead of using a matrix), taking advantage of the intact ECM produced by the cultured
chondrocytes and their adhesion factors. This innovative technique has been shown to form hyaline
cartilage in preclinical studies and is currently undergoing clinical studies in Japan [34-36] . Even though
these techniques have had great outcomes, they involve two surgical procedures: one to obtain the
cartilage biopsy and the second one for the implantation. This makes the intervention expensive and may
increase the risk of surgical complications. MSC seeded on a 3-dimensional scaffold or using the cell
sheet technology can help solve this problem. Due to endogenous cell stimulation, MSC differentiate into
[37]
cartilage, forming a cartilage-like tissue repair . Several clinical and preclinical studies using MSC seeded
on matrixes have shown positive results in forming cartilage-like tissue and alleviating symptoms [38,39] .

[40]
In 2015, Kim et al. conducted a comparative matched paired analysis comparing injected vs surgically
implanted MSC in patients with knee osteoarthritis. Patients were evaluated with Patient-Reported
Outcome Measures (PROMs), as well as a second-look arthroscopy. After a minimum follow-up of
24 months, patients who underwent MSC implantation showed better clinical and second-look arthroscopic
outcomes. Despite the positive findings with this technique, it is usually employed to repair small defects
and does not address larger areas related to OA. Problems related to the acquisition of autologous MSC and
the risk of graft-versus-host reactions with allogeneic MSC have limited their use in clinical studies.

Meniscus repair: menisci play an important role in load-bearing and load transmission to the cartilage
[41]
and subchondral bone. Approximately 15% of knee lesions are associated with damage to the meniscus .