Insights into the Secretome of Mesenchymal Stem Cells and Its Potential Applications

Eleuteri, Sharon; Fierabracci, Alessandra

doi:10.3390/ijms20184597

Cited by 227 publications

(218 citation statements)

References 144 publications

(259 reference statements)

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“…The paracrine effects of MSCs have been shown to play important role in a large number of preclinical and clinical trials [38][39][40] . We therefore used Raybio Cytokine Array analysis to analyze the expression levels of 41 human growth factor cytokines secreted by ADSCs, and compared the expression of these cytokines before and after the induction of neurosphere formation, using human NSCs as a positive control.…”

Section: Discussionmentioning

confidence: 99%

Neurospheres Induced from Human Adipose-Derived Stem Cells as a New Source of Neural Progenitor Cells

Peng

et al. 2019

Cell Transplant

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Human adipose-derived stem cells are used in regenerative medicine for treating various diseases including osteoarthritis, degenerative arthritis, cartilage or tendon injury, etc. However, their use in neurological disorders is limited, probably due to the lack of a quick and efficient induction method of transforming these cells into neural stem or progenitor cells. In this study, we reported a highly efficient and simple method to induce adipose-derived stem cells into neural progenitor cells within 12 hours, using serum-free culture combined with a well-defined induction medium (epidermal growth factor 20 ng/ml and basic fibroblast growth factor, both at 20 ng/ml, with N2 and B27 supplements). These adipose-derived stem cell-derived neural progenitor cells grow as neurospheres, can self-renew to form secondary neurospheres, and can be induced to become neurons and glial cells. Real-time polymerase chain reaction showed significantly upregulated expression of neurogenic genes Sox2 and Nestin with a moderate increase in stemness gene expression. Raybio human growth factor analysis showed a significantly upregulated expression of multiple neurogenic and angiogenic cytokines such as brain-derived neurotrophic factor, glial cell line-derived neurotrophic growth factor, nerve growth factor, basic fibroblast growth factor and vascular endothelial growth factor etc. Therefore, adipose-derived stem cell-derived neurospheres can be a new source of neural progenitor cells and hold great potential for future cell replacement therapy for treatment of various refractory neurological diseases.

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Section: Discussionmentioning

confidence: 99%

Neurospheres Induced from Human Adipose-Derived Stem Cells as a New Source of Neural Progenitor Cells

Peng

et al. 2019

Cell Transplant

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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%

“…With regards to MMP10, the MMP family of proteins are widely secreted by MSCs [42], and they play a role in breaking down the extracellular matrix [43], but recent research has shown that they have immunomodulatory effects through cleaving CC chemokines, such as CCL2 (MCP1). This process inhibits the function of CCL2, and it cannot activate an immune response but instead suppresses T-cell chemotaxis [36,42,44,45]. As MMPs have a role in cleaving CC chemokines, they may have anti-inflammatory functions in vivo.…”

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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“…In vitro, freshly isolated SVF containing ASCs secrete trophic and pro-regenerative factors, such as cytokines, growth factors, anti-inflammatory factors and extracellular vesicles harboring proteins or even microRNAs, collectively known as secretome (Fu et al, 2017). In fact, several studies have shown that the paracrine effects of ASCs and not the cells themselves, are pivotal players for tissue repair along with angiogenic and immunomodulatory properties occurring at the site of the damaged tissue (Tögel et al, 2005;Krampera, 2011;Eleuteri and Fierabracci, 2019). For example, high levels of two immunomodulatory mediators, indoleamine-pyrrole 2,3-dioxygenase (IDO) and Prostaglandin E2 (PGE2), were detected at 24 h in the supernatants from freshly isolated SVF (Nürnberger et al, 2019).…”

Section: Immunomodulatory Properties Of Ascsmentioning

confidence: 99%

Immunomodulatory Effect of Adipose-Derived Stem Cells: The Cutting Edge of Clinical Application

Ceccarelli

Pontecorvi

Anastasiadou

et al. 2020

Front. Cell Dev. Biol.

147

102

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Adipose-derived stem cells (ASCs) represent a promising tool for soft tissue engineering as well as for clinical treatment of inflammatory and autoimmune pathologies. The well-characterized multi-differentiation potential and self-renewal properties of ASCs are coupled with their immunomodulatory ability in providing therapeutic efficacy. Yet, their impact in immune or inflammatory disorders might rely both on cell contactdependent mechanisms and paracrine effects, resulting in the release of various soluble factors that regulate immune cells functions. Despite the widespread use of ASCs in clinical trials addressing several pathologies, the pathophysiological mechanisms at the basis of their clinical use have been not yet fully investigated. In particular, a thorough analysis of ASC immunomodulatory potential is mandatory. Here we explore such molecular mechanisms involved in ASC immunomodulatory properties, emphasizing the relevance of the milieu composition. We review the potential clinical use of ASC secretome as a mediator for immunomodulation, with a focus on in vitro and in vivo environmental conditions affecting clinical outcome. We describe some potential strategies for optimization of ASCs immunomodulatory capacity in clinical settings, which act either on adult stem cells gene expression and local microenvironment. Finally, we discuss the limitations of both allogeneic and autologous ASC use, highlighting the issues to be fixed in order to significantly improve the efficacy of ASC-based cell therapy.

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Insights into the Secretome of Mesenchymal Stem Cells and Its Potential Applications

Cited by 227 publications

References 144 publications

Neurospheres Induced from Human Adipose-Derived Stem Cells as a New Source of Neural Progenitor Cells

Neurospheres Induced from Human Adipose-Derived Stem Cells as a New Source of Neural Progenitor Cells

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

Immunomodulatory Effect of Adipose-Derived Stem Cells: The Cutting Edge of Clinical Application

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