Transforming growth factor-beta 1 in adipose derived stem cells conditioned medium is a dominant paracrine mediator determines hyaluronic acid and collagen expression profile

Abstract

Conditioned medium from adipose derived stem cells (ADSC-CM) stimulates both collagen synthesis and migration of fibroblasts, and accelerates wound healing in vivo. Recently, the production and secretion of growth factors has been identified as an essential function of adipose-derived stem cells (ADSCs). However, the main soluble factor of ADSC-CM which mediates paracrine effects and its underlying mechanism has not been elucidated yet. In this study, we considered transforming growth factor-beta1 (TGF-β1) as a strong candidate for paracrine effect of ADSC-CM and investigated collagen synthesis and hyaluronic acid synthase (HAS) expression. After ADSC-CM addition, collagen type I, type III, HAS and hyaluronic acid (HA) expressions on human dermal fibroblasts (HDFs) were evaluated. Furthermore, to clarify effects of TGF-β1 as a paracrine mediator, TGF-β1 antibody and external supplementary TGF-β1 were treated to HDFs. Collagens type I, type III, HAS-1 and HAS-2 mRNA expressions of HDFs were greatly increased by ADSC-CM treatment, however there was no change in TGF-β1 antibody treated HDFs compared with non-treated control. These results strongly demonstrate that TGF-β1 plays an important role as a paracrine mediator of ECM synthesis. The fact that TGF-β1 contained in ADSC-CM not only accelerates collagen deposition but also increase hyaluronic acid synthesis of HDFs through HAS-1 and HAS-2 expression was also elucidated in this study. Therefore, ADSC-CM shows promise for the treatment of cutaneous wounds and accelerates granulation formation during healing process.

Human Adipose Tissue-Derived Stromal Cell Therapy Prevents Bone Loss in Ovariectomized Nude Mouse

“…This hypothesis is supported by previous studies which revealed that several cytokines relevant to osteogenesis such as hepatocyte growth factor, vascular endothelial growth factor (VEGF), insulin-like growth factor-1, and transforming growth factor b were expressed by human ADSCs. [50][51][52] Moreover, it has been shown that ADSCs are also able to promote angiogenesis by secreting a number of pro-angiogenic factors including angiopoietin-1, stromal derived factor-1, and VEGF (reviewed in ref 53 ). These angiogenic factors may also play roles in the anabolic effect of ADSCs by recruiting host endothelial progenitor cells and stimulating neovascularization.…”

Adipose-Derived Stem Cells in Tissue Regeneration: A Review

“…What paracrine factors are involved in these studies of epidermal/dermal formation remain unknown but possible paracrine factors may include HGF, VEGF, TGF 1, TGF 3, G-CSF, GM-CSF, IL6, and IL8 [292]. In support of this, Jung and colleagues have reported that conditioned medium from ASCs can increase CNI, CNIII, and hyaluronic acid synthesis by human dermal fibroblasts and that neutralizing antibodies to TGF 1 can abolish this effect [296].…”

Dermal Adipocytes: From Irrelevance to Metabolic Targets?

“…Proposed mechanisms include the secretion of TGF-β1 by ADSCs, which provides significant inhibition of the melanin synthesis through a downregulation of tyrosinase and expression of tyrosinase-related protein 1 (TRP1). In addition, TGF-β1 is a well-known dominant paracrine mediator, which determines the hyaluronic acid and collagen expression profiles [44]. Another group recently confirmed this effect and proposed that inhibition of melanin synthesis can be realized via interleukin-6 [45].…”