Prostemics Research Institute, Seoul, Korea
Expert Opin. Biol. Ther. (2009) 9(7):879-887
Won-Serk Kim, Byung-Soon Park† & Jong-Hyuk Sung†
Regenerative medicine that uses the body’s own stem cells and growth factors is an alternative therapeutic strategy for repair of damaged tissue, and is becoming a predominant cell-based therapy. The limited availability of human cells capable of self-renewal and differentiation is a barrier to the expansion and development of tissue engineering; adipose-derived stem cells (ADSCs), however, offer the potential for a workable solution to this dilemma and could result in the regeneration of damaged tissue [1,2]. ADSCs can be easily obtained from liposuction of human adipose tissue, can be cultured on a large scale, and can display multi-lineage developmental plasticity [3-5]. ADSCs secrete various growth factors that control and manage damaged neighboring cells, and this has been identified as an essential function of ADSCs [6-8]. Conditioned medium from ADSC cultures (ADSC-CM) activates dermal fibroblasts and keratinocytes, and can repair the skin through a paracrine mechanism (Figure 1) [6-10]. For example, ADSC-CM stimulated both collagen synthesis and migration of dermal fibroblasts, which improved wrinkling and accelerated wound-healing in animal models [7,9]. ADSC-CM also inhibited melanogenesis in B16 melanoma cells, and exhibited a skin-whitening effect . ADSC-derived secretory factors protected dermal fibroblasts from oxidative stress induced by chemical and UVB irradiation [6,7]. Recently, it has been demonstrated that ADSC-CM promoted hair growth, which was enhanced by hypoxia (our unpublished data). Based on our previous studies, recent research developments concerning the wound- healing and antioxidant effects of ADSCs and their secretory factors are briefly described in this review.
The wound-healing and antioxidant effect of ADSCs and ADSC-derived secretory factors were reviewed in this paper. To date, application of ADSCs has been investigated mainlyin vitro and animal studies, and the results are satisfactory. However, clinical application of cultured ADSCs in human skin is in its early stages and can be hazardous considering the risk of inducing cancer. In addition, ADSCs are difficult both to handle and to commercialize from an industrial point of view, so new methods and materials to overcome these limitations are needed. Instead, secreted proteins of ADSCs have numerous advantages over cell-based therapies and have great potential in skin repair, because they can be stored with long-term stability and are relatively devoid of safety issues. The use of stem cell protein also enhances the scalability of production and the potential of developing low-cost therapeutics. Until now, however, characterization of active proteins involved in the wound-healing and antioxidant functions of ADSCs has been in its early stages due to low assay sensitivity of proteomic analysis and relatively low protein concentrations in the ADSC-CM. Therefore, identification of active proteins from ADSC-CM will be the next goal of our research, and drug development using these proteins should reveal many effective strategies for skin repair and regeneration in the future.