A therapeutic modality currently being developed for melasma is secretome. Secretome is a bioactive molecule secreted by mesenchymal stem cells in a conditioned medium containing a large number of growth factors, cytokines, various macromolecules, and extracellular vesicles, including microvesicles and exosomes, that can stimulate various biological reactions, particularly in modulating new tissue formation. Secretome can provide a depigmenting effect by increasing the proliferation and migration of epidermal keratinocytes, which contain melanin pigment, in line with increased fibroblast synthesis.
Secretomes contain various cytokines and growth factors, one of which is transforming growth factor (TGF)-. TGF- is primarily secreted by fibroblasts (FB) and, to a lesser extent, by keratinocytes, and plays a crucial role in regulating melanocyte function. TGF- has been reported to inhibit cAMP/protein kinase A signaling and induce GLI2, which then suppresses microphthalmia-associated transcription factor (MITF), a central transcription factor in melanogenesis. A study by Moon et al. in Korea examined TGF-3. Moon et al. examined the effects of TGF-3 on melanogenesis in human melanocytes co-cultured with skin cells irradiated with ultraviolet (UV) light, and in UV-irradiated human skin. The results showed that UVB irradiation or stem cell factor (SCF)/endothelin-1 (ET-1) increased melanogenesis. TGF-3 effectively inhibited melanin accumulation and tyrosinase activity by downregulating the extracellular signal-regulated kinase (ERK)/microphthalmia-associated transcription factor (MITF) pathway. TGF-3 increased the expression of keratinocyte differentiation markers.
Mechanistically, TGF-3 inhibits melanogenesis by inhibiting MITF expression, which is regulated by ERK. TGF-1 reduces MITF but at the risk of inducing skin fibrosis. However, in the study by Moon et al., the aforementioned TGF Beta 1 function was not found in TGF-3. Furthermore, TGF-3 restored skin differentiation function in UV-irradiated keratinocytes.
To date, there have been no clinical trials comparing intradermal injection of concentrated secretome with intradermal injection of concentrated secretome with the addition of TGF-3 as a melasma therapy in Indonesia, thus encouraging researchers to conduct further research.