Placenta Mesenchymal Stem Cell Derived Exosomes Confer Plasticity on Fibroblasts

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-derived 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 adipocyte-differentiation of NHDF were evaluated by alkaline phosphatase (ALP), and Alizarin red S- and oil red O-staining, respectively. The expression of osteoblast- and adipocyte-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 osteoblastic and adipocyte-differentiation 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 adipocyte-differentiation. It shows a new feature of MSCs and the possibility of clinical application of MSC-exo. J. Cell. Biochem. 117: 1658-1670, 2016. © 2015 Wiley Periodicals, Inc.

Role of stem cell derived exosomes in tumor biology

“…For example, exosomal transfer of PTEN decreases cell proliferation in recipient cells . In line, stem cell derived exosomes carry pluripotent transcription factors such as Nanog, Oct‐4 and Wnt family proteins which can promote self‐renewal, stemness in recipient cells via changes in cellular plasticity . Importantly, since both CSCs, and MSCs are known regulators of different tumor hallmarks, it is plausible that MSCs, CSCs derived exosomes may as well prime tumor microenvironment and modulate tumor functions.…”

“…26 In line, stem cell derived exosomes carry pluripotent transcription factors such as Nanog, Oct-4 and Wnt family proteins which can promote self-renewal, stemness in recipient cells via changes in cellular plasticity. 27,28 Importantly, since both CSCs, and MSCs are known regulators of different tumor hallmarks, it is plausible that MSCs, CSCs derived exosomes may as well prime tumor microenvironment and modulate tumor functions. In this review, we focus on the role of two prominent stem cell populations-CSCs, and MSCs-derived exosomes in regulating tumor pathobiology.…”

Human Mesenchymal Stem Cells Promote Ischemic Repairment and Angiogenesis of Diabetic Foot Through Exosome miRNA-21-5p

“…Exosomes were isolated from the collected culture supernatant using ultracentrifugation by referring literatures [19] . Brie y, to remove cellular debris and proteins, the supernatant was sequentially centrifuged at 300g for 5 min, 2000g for 10 min, and then 10000g for 20 min.…”

A new approach in stem cell research—Exosomes: Their mechanism of action via cellular pathways

“…Embryonic stem cells (ESCs) (Khan et al, 2015), IPSCs , human bone marrow mesenchymal stem cells (hBMSCs) (Xu et al, 2014), human umbilical cord MSCs (hUMSCs) (Zhang et al, 2015a), placenta MSCs (Tooi et al, 2016), hESCs-derived c-Myc-immortalized MSCs (Lai et al, 2016), IPSCs-derived MSCs (Zhang et al, 2015b), GATA-4 overexpressing MSCs (Yu et al, 2015), hematopoietic progenitor cells (Sahoo et al, 2011), human endothelial progenitor cells , human cardiac progenitor cells (Barile et al, 2014), cardiosphere-derived cells, a source of multipotent and progenitor cells (Lang et al, 2016), and differentiating neural progenitor cells (Takeda and Xu, 2015) are the stem cells which have been previously evaluated to this end. Embryonic stem cells (ESCs) (Khan et al, 2015), IPSCs , human bone marrow mesenchymal stem cells (hBMSCs) (Xu et al, 2014), human umbilical cord MSCs (hUMSCs) (Zhang et al, 2015a), placenta MSCs (Tooi et al, 2016), hESCs-derived c-Myc-immortalized MSCs (Lai et al, 2016), IPSCs-derived MSCs (Zhang et al, 2015b), GATA-4 overexpressing MSCs (Yu et al, 2015), hematopoietic progenitor cells (Sahoo et al, 2011), human endothelial progenitor cells , human cardiac progenitor cells (Barile et al, 2014), cardiosphere-derived cells, a source of multipotent and progenitor cells (Lang et al, 2016), and differentiating neural progenitor cells (Takeda and Xu, 2015) are the stem cells which have been previously evaluated to this end.…”

“…Literature reveals a wide variety of stem cell species which were used for isolation and characterization of exosomes. Embryonic stem cells (ESCs) (Khan et al, 2015), IPSCs , human bone marrow mesenchymal stem cells (hBMSCs) (Xu et al, 2014), human umbilical cord MSCs (hUMSCs) (Zhang et al, 2015a), placenta MSCs (Tooi et al, 2016), hESCs-derived c-Myc-immortalized MSCs (Lai et al, 2016), IPSCs-derived MSCs (Zhang et al, 2015b), GATA-4 overexpressing MSCs (Yu et al, 2015), hematopoietic progenitor cells (Sahoo et al, 2011), human endothelial progenitor cells , human cardiac progenitor cells (Barile et al, 2014), cardiosphere-derived cells, a source of multipotent and progenitor cells (Lang et al, 2016), and differentiating neural progenitor cells (Takeda and Xu, 2015) are the stem cells which have been previously evaluated to this end.…”