Exosomes from Placental Mesenchymal Stem Cells Confer Plasticity to Fibroblasts

Journal of Cellular Biochemistry
DOI: 10.1002/jcb.25459

Cells have the ability to internalize small portion of their membranes into small vesicles called endosomes. Once inside the cell, these endosomes can then internalize bits of their own membranes to form a kind of vesicle-within-a-vesicle structure called a “multivesicular endosomes” or MVEs. Cells can load up these MVEs with various proteins and RNAs and lipids, and then secrete them into their environment. Once released, these former MVEs become known as “extracellular vesicles” or EVs, and the smallest of the EVs are known as exosomes.


Neighboring cells can take up exosomes released by nearby or far-flung cells and the proteins and RNAs delivered by the exosomes can elicit profound changes in cell behavior. Therefore, exosomes act as agents of cell-cell communication. Detection of exosomes from cancer cells into blood, or other bodily fluids can provide diagnostic insights into the diagnosis of cancers. Also exosomes from stem cells can augment tissue healing and repair (see here).

Exosomes from mesenchymal stem cells (MSCs) are released into the culture medium when MSCs are grown in the laboratory. Exosome-containing culture medium is often referred to as “conditioned medium” and in this case it is conditioned medium from MSCs, which we will refer to as MSC-CM. MSC-CM has been reported to enhance wound healing in several different experiments.

In a new study by Motohiro Komaki and his colleagues at the Tokyo Medical and Dental University, in Tokyo, Japan has examined the effects of exosomes from human placenta MSCs in a controlled culture system to better characterize the biological roles of these exosomes.

In this study, placental MSCs were from donated human placenta from newborn babies by means of enzymatic digestion. Exosomes were prepared from these placental MSCs (PlaMSCs) by growing the cells in culture and then subjecting the conditioned culture medium to ultracentrifugation. Exosomes, fortunately, are relatively easy to isolate and can be frozen and stored quite effectively without loss of function.

These isolated PlaMSC exosomes were then given to cultured human dermal fibroblasts. Changes in gene expression were then ascertained by real-time reverse transcriptase PCR analysis (real-time PCR).

After incubating fibroblasts with exosomes from PlaMSCs, the expression of stemness-related genes, such as OCT4 and NANOG were significantly increased. These exosomes also stimulated the differentiation of these fibroblasts into bone cells and fat cells when the cells were subjected to bone and fat induction media. The fibroblasts expressed bone-specific and fat-specific genes and enzymes.

Thus, these experiments showed that exosomes from PlaMSCs increased the expression of the stemness genes OCT4 and NANOG in fibroblasts, which normally do not express these genes. Consequently, these exosomes influence ability of fibroblasts to differentiate in both bone and fat cells. This work demonstrates a new feature of MSCs and their exosomes, and suggests new possible clinical applications for MSC exosomes.