TGF-β1-treated ADSCs-CM promotes expression of type I collagen and MMP-1, migration of human skin fibroblasts, and wound healing in vitro and in vivo

TGF-β1-treated ADSCs-CM promotes expression of type I collagen and MMP-1, migration of human skin fibroblasts, and wound healing in vitro and in vivo
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DOI:
10.3892/ijmm_00000540
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发表时间:
2010-12-01
影响因子:
5.4
通讯作者:
Lee, Kyu-Suk
Lee, Kyu-Suk
中科院分区:
医学3区
文献类型:
--
作者:
Cho, Jae-We;Kang, Min-Chul;Lee, Kyu-Suk

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来自脂肪来源的干细胞(ADSC)的条件培养基刺激真皮成纤维细胞的胶原合成和迁移。然而,与未处理的ADSCs-CM相比,来自肿瘤生长因子(TGF)-β 1处理的ADSCs(TGF-β 1处理的ADSCs-CM)的条件培养基是否诱导成纤维细胞中I型胶原蛋白、基质金属蛋白酶-1(MMP-1)和迁移以及细胞周期调节蛋白的表达增加仍是未知的。我们的数据显示,与未处理的ADSCs-CM相比,TGF-β 1处理的ADSCs-CM有效地促进人皮肤成纤维细胞的增殖和迁移。此外,与未处理的ADSCs-CM相比,TGF-β 1处理的ADSCs-CM在成纤维细胞中的MMP-1表达显著增加。TGF-β 1处理的ADSCs-CM在成纤维细胞中的型胶原蛋白表达略有增加。TGF-β 1处理的ADSCs-CM处理后,GI/S期转换的细胞周期调节因子的表达没有明显改变。最后,在无毛小鼠中使用4-mm穿刺活检制备人工伤口,并将TGF-β 1处理的ADSCs-CM注射到伤口区域。注射TGF-β 1处理的ADSCs-CM促进无毛小鼠的伤口愈合过程。总之,我们的数据表明,TGF-β 1处理的ADSCs-CM诱导I型胶原和MMP-1的上调,促进皮肤成纤维细胞的迁移,从而促进体内伤口愈合过程。我们的数据表明,TGF-β 1处理的ADSCs-CM将是伤口愈合加速剂的组分。
Conditioned medium from adipose-derived stem cells (ADSCs) stimulates both collagen synthesis and migration of dermal fibroblasts. However, it is still unknown whether conditioned media from tumor growth factor (TGF)-beta 1-treated ADSCs (TGF-beta 1-treated ADSCs-CM) induces increased expression of type I collagen, matrix metalloproteinase-1 (MMP-1), and migration as well as cell cycle regulatory proteins in fibroblasts, compared to non-treated ADSCs-CM. Our data showed that TGF-beta 1-treated ADSCs-CM promoted effectively the proliferation and migration of human skin fibroblasts, compared to non-treated ADSCs-CM. In addition the expression of MMP-1 were markedly increased by treatment of TGF-beta 1-treated ADSCs-CM in fibroblasts, compared to non-treated ADSCs-CM. Expression of type collagen protein were slightly increased by treatment of TGF-beta 1-treated ADSCs-CM in fibroblasts. The expression of cell cycle regulators of GI/S phase transition were not markedly altered by treatment of TGF-beta 1-treated ADSCs-CM. Finally, artificial wounds were made using a 4-mm punch biopsy in hairless mice and TGF-beta 1-treated ADSCs-CM were injected into the wound area. The injection of TGF-beta 1-treated ADSCs-CM promoted the wound healing process in hairless mice. Taken together, our data indicated that TGF-beta 1-treated ADSCs-CM induced up-regulation of type I collagen and MMP-1, promoted the migration of skin fibroblasts, and thereby promoted the wound healing process in vivo. Our data indicate that TGF-beta 1-treated ADSCs-CM will be a component for a wound healing accelerating agent.