Stem Cells Therapy as Anti-scar Treatment
Scars are a consequence of cutaneous wound healing that can be both unsightly and detrimental to the function of the tissue. Scar tissue is generated by excessive deposition of extracellular matrix tissue by wound healing fibroblasts and myofibroblasts. Hypertrophic scars generally occur after injury to the deep layers of the dermis. Scarring is not a necessary process to repair the dermal tissues. Rather, scar tissue forms due to specific mechanisms that occur during the adult wound healing process and are modulated primarily by the inflammatory response at the site of injury.
Excessive scarring (Hypertrophic Scars or Keloid), first described in the Smith papyrus about 1700 BC, it may occur after any type of injury including burns, lacerations, abrasions, piercings, surgical incisions, or injections. Excessive scars like hypertrophic scars or keloids are scars that present with an excess of dermal collagen, rising above skin level. Such lesions not only are cosmetically unattractive, but may also limit joint function and cause uncomfortable symptoms such as pain and pruritis. The resulting psychological burden affects the patient’s quality of life and escalates health care costs. Although the definitive process underlying such scar formation is yet to be elucidated, the upregulated, exaggerated inflammatory response has been found to be a critical step in achieving excessive scars.
Scars are characterized by a different appearance to the surrounding skin: discoloration, stiffness and roughness are features of scarring.
Lipofilling or lipotransfer is a novel and promising treatment method for reduction or prevention of dermal scars after injury. Studies shows evidence supports the scar reducing properties of adipose tissue grafts. However, the underlying mechanism by which lipofilling improves scar aspect and reduces neuropathic scar pain remains largely undiscovered.
Adipose-derived stem cells (ADSCs) are often described to be responsible for this therapeutic effect of lipofilling. The anti-scarring function of MSCs is related to the inhibition of both myofibroblast differentiation and NO production. The clinical efficacy of lipofilling in scar areas is determined by improvement of the appearance of a scar, such as size, thickness, stiffness, discoloration of the scar. In the case of painful scars, this effect can also be measured by a decrease in pain. Efficacy of lipofilling as a means for pain reduction was investigated, most but not all studies reported a significant reduction of pain after treatment of painful scars.
The most pioneering clinical work for this procedure is taking place in Japan, by using cultured ADSCs (stem cells taking it from your body fat and send to specialised lab for incubation and multiplying it to a sufficient numbers for the treatment area) to inject underneath the scar area and this technique is not only good for treatment of wound scar but, also acne scars and for filling in frown lines and wrinkles.
The efficacy of lipofilling to improve scar appearance has been investigated in multiple studies and all some degree of amelioration in scar appearance after lipofilling & that mean the scars became less different from normal skin and/or became less visible, also most studies has reported that risks of lipofilling in scar areas are rather low or even none.
Mesenchymal Stem Cells can increase the wound healing process and inhibit hyperplastic scar formation by down-regulation of TGF-β1, collagen type I and III. Mesenchymal stem cells derived from Adipose Tissue (ADSCs) preferable for this usage compared to mesenchymal stem cells derived from bone marrow BmSCs, as the relatively easy harvesting of a large amounts of adipose tissue, less pain during harvesting, and the multi-lineage capacity of differentiating into several cell types.
Chen et al. (2016) observed that ADSCs made the hyperplastic scars smaller, flatter, and softer in comparison to control group in his study. A similar finding in Dososaputro et al (2017) study.
Microscopically, scars display a loss of rete ridges, sebaceous glands and hair follicles. Also, they are characterized by increased dermal and epidermal thickness. The epidermal thickening is caused by excessive proliferation of keratinocytes. In the dermis, the thickening is caused by excessive extracellular matrix (ECM) production by myofibroblasts, mainly consisting of collagen type I, not only there is an increase in the amount of collagens, but also in the collagen fibre thickness, maturation and degree of disorganization. However, if myofibroblasts persist, scarring will be the end result. Adipocyte-Derived Stem Cells ADSCs significantly decreased collagen expression and deposition, and inhibited the trans-differentiation of fibroblasts, also, can inhibit the myofibroblast so, the proliferation, production and contraction of these fibroblasts were reduced, which indicates that growth factors and cytokines of ADSC have the ability to prevent or even to reverse dermal scarring.