Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Aug 22:4:83.
doi: 10.3389/fcell.2016.00083. eCollection 2016.

Stem Cell-Derived Extracellular Vesicles and Immune-Modulation

Jacopo Burrello  1 , Silvia Monticone  1 , Chiara Gai  1 , Yonathan Gomez  1 , Sharad Kholia  1 , Giovanni Camussi  1
Affiliations
Review

Stem Cell-Derived Extracellular Vesicles and Immune-Modulation

Jacopo Burrello et al. Front Cell Dev Biol. .

Abstract

Extra-cellular vesicles (EVs) are bilayer membrane structures enriched with proteins, nucleic acids, and other active molecules and have been implicated in many physiological and pathological processes over the past decade. Recently, evidence suggests EVs to play a more dichotomic role in the regulation of the immune system, whereby an immune response may be enhanced or supressed by EVs depending on their cell of origin and its functional state. EVs derived from antigen (Ag)-presenting cells for instance, have been involved in both innate and acquired (or adaptive) immune responses, as Ag carriers or presenters, or as vehicles for delivering active signaling molecules. On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by carrying immuno-modulatory effectors, such as transcriptional factors, non-coding RNA (Species), and cytokines. In addition, stem cell-derived EVs have also been reported to impair dendritic cell maturation and to regulate the activation, differentiation, and proliferation of B cells. They have been shown to control natural killer cell activity and to suppress the innate immune response (IIR). Studies reporting the role of EVs on T lymphocyte modulation are controversial. Discrepancy in literature may be due to stem cell culture conditions, methods of EV purification, EV molecular content, and functional state of both parental and target cells. However, mesenchymal stem cell-derived EVs were shown to play a more suppressive role by shifting T cells from an activated to a T regulatory phenotype. In this review, we will discuss how stem cell-derived EVs may contribute toward the modulation of the immune response. Collectively, stem cell-derived EVs mainly exhibit an inhibitory effect on the immune system.

Keywords: exosomes; extracellular vesicles; immune system; immuno-modulation; stem cells.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Biogenesis of EVs and their immuno-modulatory effects. EVs, Extracellular Vesicles; Ag, Antigen; IL, Interleukin; Ab, Antibodies.
See this image and copyright information in PMC

References

    1. Aggarwal S., Pittenger M. F. (2005). Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105, 1815–1822. 10.1182/blood-2004-04-1559 - DOI - PubMed
    1. Aliotta J. M., Pereira M., Johnson K. W., de Paz N., Dooner M. S., Puente N., et al. . (2010). Microvesicle entry into marrow cells mediates tissue-specific changes in mRNA by direct delivery of mRNA and induction of transcription. Exp. Hematol. 38, 233–245. 10.1016/j.exphem.2010.01.002 - DOI - PMC - PubMed
    1. Alvarez C. V., Garcia-Lavandeira M., Garcia-Rendueles M. E., Diaz-Rodriguez E., Garcia-Rendueles A. R., Perez-Romero S., et al. . (2012). Defining stem cell types: understanding the therapeutic potential of ESCs, ASCs, and iPS cells. J. Mol. Endocrinol. 49, R89–R111. 10.1530/JME-12-0072 - DOI - PubMed
    1. Amarnath S., Foley J. E., Farthing D. E., Gress R. E., Laurence A., Eckhaus M. A., et al. . (2015). Bone marrow-derived mesenchymal stromal cells harness purinergenic signaling to tolerize human Th1 cells in vivo. Stem Cells 33, 1200–1212. 10.1002/stem.1934 - DOI - PMC - PubMed
    1. Andre F., Schartz N. E., Movassagh M., Flament C., Pautier P., Morice P., et al. . (2002). Malignant effusions and immunogenic tumour-derived exosomes. Lancet 360, 295–305. 10.1016/S0140-6736(02)09552-1 - DOI - PubMed