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Velasquillo et al. Plast Aesthet Res 2020;7:31  I  http://dx.doi.org/10.20517/2347-9264.2020.30                                   Page 3 of 14

               been proposed that the homing activity of MSC creates immune-privileged sites that limit the infiltration
                                                                                             [8]
               of CD4+ and CD8+ T cells in tissues, thus limiting damage and promoting regeneration . Meanwhile,
               heterologous MSC from bone marrow (BM-MSC) have been used for the treatment of pseudoarthrosis and
               have been proved to promote healing of femoral fractures in a claudication animal model. Heterologous
               BM-MSC reached the lesion 24 h after being infused, and later promoted a periosteal reaction that lead
               to fracture consolidation and cartilage formation 120 days after the infusion. In comparison, BM-MSC
                                              [9]
               alone formed a fibro-osteoid tissue . These effects lead us to elucidate that the use of autologous versus
               allogeneic MSC will depend on the required clinical outcome.

               In recent years, clinical implications and advantages in the use of stromal vascular fraction (SVF) have
               opened new alternatives for tissue engineering in craniofacial or degenerative diseases. The differences
               between SVF and adipose-derived MSC (AD-MSC) are that an SVF is a freshly harvested, heterogeneous
               population of cells directly isolated from lipoaspirates by mechanical or enzymatic disaggregation that
                                                                                                       [10]
               contains stromal cells (15%-30%), erythrocytes, granulocytes, monocytes, pericytes, and endothelial cells .
               AD-MSC are a cultured, more homogeneous subpopulation of cells resulting from a culture selection and
               in vitro expansion. On the other hand, compared to BM-MSC, adipose tissue contains 100-500 fold more
               MSC, and SVF contains 4-6 fold more MSC, whose therapeutic impact, angiogenic stimulation, T-cell
                                                                                               [11]
               regulation and reduction of IL-10 production represent a feasible source for tissue engineering .

               Although there are still difficulties to establish the proper dose and clinical safety protocols, there is no
               doubt of the potential of AD-MSC to accelerate healing processes. Therapeutic efforts for the treatment of
               degenerative diseases have moved research groups to develop semi-automated, surgically-closed systems
               to obtain SVF during surgeries with minimal laboratory equipment requirements that will enable the
                                                                                         [12]
               application and implantation of autologous or heterologous MSC for tissue engineering .

               Degenerative diseases
               A degenerative disease is a pathology in which the function or structure of the affected tissues or organs
                               [1]
               worsens over time . As mentioned earlier, stem cells have changed the course of these diseases and have
               become an alternative treatment for degenerative disorders.


               Osteoarthritis
               Osteoarthritis (OA) is a condition that causes joints to hurt and become stiff. It is the most common cause
               of arthritis worldwide, and it mainly affects knees (85%), hips, hands, and feet. Approximately 240 million
                                        [13]
               people in the world have OA . 5% of adults worldwide have either hip or knee OA. These numbers will
                                                                    [14]
               increase as the population ages and the obesity rates increases . Pain is the main symptom that typically
               leads patients to seek medical care and guides clinicians into treatment decision-making as well. Pain can
               be so intense, patients become unable to work, making OA the fourth leading cause of years lived with
                                [15]
               disability worldwide .
               OA has been part of the changes of articular cartilage, but that concept has evolved, now considering
               the whole joint [16,17] . Some of the structural damages of joints are (1) loss of cartilage; (2) osteophyte
                                                                             [17]
               formation; (3) subchondral bone changes; and (4) meniscal alterations . Chondral erosions caused by
               overload or abnormal joint kinematics turn into fissures. In an attempt to repair these lesions, hypertrophic
               chondrocytes increase their synthetic activity, but, by doing that, they increase the production of
               proinflammatory mediators and degradation products. These molecules stimulate surrounding synovium,
               increasing its proliferation, and proinflammatory response as well. All inflammation mediators favor
               endochondral ossification, causing bone overgrowth and osteophyte formation. Pain comes from the
                                                                                          [16]
               peripheral nociceptors sensing ongoing tissue injury, as well as inflammation in the joint .
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