J Cell Biochem. 2015 Dec 7. doi: 10.1002/jcb.25459. [Epub ahead of print]

Placenta Mesenchymal Stem Cell Derived Exosomes Confer Plasticity on Fibroblasts.

Tooi M¹, Komaki M², Morioka C³, Honda I⁴, Iwasaki K², Yokoyama N⁵, Ayame H⁵, Izumi Y¹, Morita I⁶.

Author information

Abstract

Mesenchymal stem cell (MSC)-conditioned medium (MSC-CM) has been reported to enhance wound healing. Exosomes contain nucleic acids, proteins, and lipids, and function as an intercellular communication vehicle for mediating some paracrine effects. However, the function of MSC-exosomes (MSC-exo) remains elusive. In this study, we isolated human placenta MSC (PlaMSC)-derived exosomes (PlaMSC-exo) and examined their function in vitro. PlaMSCs were isolated from human term placenta using enzymatic digestion. PlaMSC-exo were prepared from the conditioned medium of PlaMSC (PlaMSC-CM) by ultracentrifugation. The expression of stemness-related genes, such as OCT4 and NANOG, in normal adult human dermal fibroblasts (NHDF) after incubation with PlaMSC-exo was measured by real-time reverse transcriptase PCR analysis (real-time PCR). The effect of PlaMSC-exo on Oct4 transcription activity was assessed using Oct4-EGFP reporter mice-derived dermal fibroblasts. The stimulating effects of PlaMSC-exo on osteoblastic and adipogenic differentiation of NHDF were evaluated by alkaline phosphatase (ALP), and Alizarin red S- and oil red O-staining, respectively. The expression of osteogenic and adipogenic related genes was also assessed by real-time PCR. The treatment of NHDF with PlaMSC-exo significantly upregulated OCT4 and NANOG mRNA expression. PlaMSC-exo also enhanced Oct4 transcription. The NHDF treated with PlaMSC-exo exhibited osteogenic and adipogenic differentiation of NHDF in osteogenic and adipogenic induction media. PlaMSC-exo increase the expression of OCT4 and NANOG mRNA in fibroblasts. As a result, PlaMSC-exo influence the differentiation competence of fibroblasts to both osteoblastic and adipogenic differentiation. It shows a new feature of MSCs and the possibility of clinical application of MSC-exo. This article is protected by copyright. All rights reserved.