Exosomes from hypoxia-treated human adipose-derived mesenchymal stem cells enhance angiogenesis through VEGF/VEGF-R

Han, Yang; Ren, Jing; Bai, Yun; Pei, Xuetao; Han, Yan

doi:10.1016/j.biocel.2019.01.017

Cited by 208 publications

(171 citation statements)

References 30 publications

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“…Despite UCMSCs having similar PDTs between conditions, hypoxia is still worth exploring as animal studies have shown that UCMSCs, grown in hypoxia, have a higher angiogenic potential in the treatment of mouse hindlimb ischaemia [33,34] and rat spinal cord injury in comparison to UCMSCs grown in normoxia [35]. Indeed, the pro-angiogenic protein VEGF-A [36][37][38], was expressed in all conditions but upregulated in hypoxic/primed EV samples. VEGF-A is a well-documented hypoxic-induced response [39], there might be other hypoxic related changes in the EVs that weren't detected in this array; an array covering a broader repertoire of proteins might have identified more hypoxic-mediated changes.…”

Section: Discussionmentioning

confidence: 99%

Pro-Inflammatory Priming of Umbilical Cord Mesenchymal Stromal Cells Alters the Protein Cargo of Their Extracellular Vesicles

Hyland

Mennan

Wilson

et al. 2020

Cells

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Umbilical cord mesenchymal stromal cells (UCMSCs) have shown an ability to modulate the immune system through the secretion of paracrine mediators, such as extracellular vesicles (EVs). However, the culture conditions that UCMSCs are grown in can alter their secretome and thereby affect their immunomodulatory potential. UCMSCs are commonly cultured at 21% O 2 in vitro, but recent research is exploring their growth at lower oxygen conditions to emulate circulating oxygen levels in vivo. Additionally, a pro-inflammatory culture environment is known to enhance UCMSC anti-inflammatory potential. Therefore, this paper examined EVs from UCMSCs grown in normal oxygen (21% O 2 ), low oxygen (5% O 2 ) and pro-inflammatory conditions to see the impact of culture conditions on the EV profile. EVs were isolated from UCMSC conditioned media and characterised based on size, morphology and surface marker expression. EV protein cargo was analysed using a proximity-based extension assay. Results showed that EVs had a similar size and morphology. Differences were found in EV protein cargo, with pro-inflammatory primed EVs showing an increase in proteins associated with chemotaxis and angiogenesis. This showed that the UCMSC culture environment could alter the EV protein profile and might have downstream implications for their functions in immunomodulation.

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Section: Discussionmentioning

confidence: 99%

Pro-Inflammatory Priming of Umbilical Cord Mesenchymal Stromal Cells Alters the Protein Cargo of Their Extracellular Vesicles

Hyland

Mennan

Wilson

et al. 2020

Cells

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“…Thus, differences have been described between the secretome of the human bone-marrow mesenchymal stem cells (BM-MSC), adiposetissue stem cells (ATSC), and umbilical-cord perivascular cells (UCPC) (Pires et al, 2016). Cells grown under hypoxia produce exosomes with enhanced angiogenic, regenerative, and immunomodulating capacities (Li et al, 2015a;Han et al, 2019;Showalter et al, 2019). Besides, it has been recently described that even the type of culture as standard monolayer or as multilayers/globules (sometimes referred with the misleading names of 2D and 3D, respectively, since we live in a 3D world), may also modulate the properties of the exosomes produced by the MSC.…”

Section: Properties and Therapeutic Potential Of Mscmentioning

confidence: 99%

“…The proangiogenic capacity of the EV for regenerative medicine can be enhanced by preconditioning the producing cells. It is known that hypoxia is an angiogenic inducer (Han et al, 2019). Thus, MSC derived from bone marrow have been preconditioned with deferoxamine (DFO) for 48 h. That is a classical hypoxia-mimetic agent, which activates genes induced by hypoxia (Templeton and Liu, 2003).…”

Section: Angiogenesismentioning

confidence: 99%

Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing

Casado-Díaz

Quesada‐Gómez

Dorado

2020

Front. Bioeng. Biotechnol.

198

160

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The cells secrete extracellular vesicles (EV) that may have an endosomal origin, or from evaginations of the plasma membrane. The former are usually called exosomes, with sizes ranging from 50 to 100 nm. These EV contain a lipid bilayer associated to membrane proteins. Molecules such as nucleic acids (DNA, mRNA, miRNA, lncRNA, etc.) and proteins may be stored inside. The EV composition depends on the producer cell type and its physiological conditions. Through them, the cells modify their microenvironment and the behavior of neighboring cells. That is accomplished by transferring factors that modulate different metabolic and signaling pathways. Due to their properties, EV can be applied as a diagnostic and therapeutic tool in medicine. The mesenchymal stromal cells (MSC) have immunomodulatory properties and a high regenerative capacity. These features are linked to their paracrine activity and EV secretion. Therefore, research on exosomes produced by MSC has been intensified for use in cell-free regenerative medicine. In this area, the use of EV for the treatment of chronic skin ulcers (CSU) has been proposed. Such sores occur when normal healing does not resolve properly. That is usually due to excessive prolongation of the inflammatory phase. These ulcers are associated with aging and diseases, such as diabetes, so their prevalence is increasing with the one of such latter disease, mainly in developed countries. This has very important socio-economic repercussions. In this review, we show that the application of MSC-derived EV for the treatment of CSU has positive effects, including accelerating healing and decreasing scar formation. This is because the EV have immunosuppressive and immunomodulatory properties. Likewise, they have the ability to activate the angiogenesis, proliferation, migration, and differentiation of the main cell types involved in skin regeneration. They include endothelial cells, fibroblasts, and keratinocytes. Most of the studies carried out so far are preclinical. Therefore, there is a need to advance more in the knowledge about the conditions of production, isolation, and action mechanisms of EV. Interestingly, their potential application in the treatment of CSU opens the door for the design of new highly effective therapeutic strategies.

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“…Increases in both mRNA and protein levels of EGF, vascular endothelial growth factor (VEGF), fibroblast growth factor and their receptors (VEGF‐R2 and VEGF‐R3), angiopoietin‐1, tyrosine kinase, monocyte chemoattractant protein 2, and monocyte chemoattractant protein 4 were observed in the grafted tissue at 30 days after injection with PC‐ADMSCs‐Exo. They revealed that hypoxia‐treated human ADMSCs improve angiogenesis and survival in the fat grafts through regulating VEGF/VEGF‐R signaling pathways and attenuating inflammation, respectively …”

Section: Exosomes In Hypoxia Conditionsmentioning

confidence: 99%

How hypoxia regulate exosomes in ischemic diseases and cancer microenvironment?

et al. 2020

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Exosomes, as natural occurring vesicles, play highly important roles in the behavior and fate of ischemic diseases and different tumors. Secretion, composition, and function of exosomes are remarkably influenced by hypoxia in ischemic diseases and tumor microenvironment. Exosomes secreted from hypoxic cells affect development, growth, angiogenesis, and progression in ischemic diseases and tumors through a variety of signaling pathways. In this review article, we discuss how hypoxia affects the quantity and quality of exosomes, and review the mechanisms by which hypoxic cell‐derived exosomes regulate ischemic cell behaviors in both cancerous and noncancerous cells.

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Exosomes from hypoxia-treated human adipose-derived mesenchymal stem cells enhance angiogenesis through VEGF/VEGF-R

Cited by 208 publications

References 30 publications

Pro-Inflammatory Priming of Umbilical Cord Mesenchymal Stromal Cells Alters the Protein Cargo of Their Extracellular Vesicles

Pro-Inflammatory Priming of Umbilical Cord Mesenchymal Stromal Cells Alters the Protein Cargo of Their Extracellular Vesicles

Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing

How hypoxia regulate exosomes in ischemic diseases and cancer microenvironment?

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