Wharton’s Jelly Mesenchymal Stromal/Stem Cells Derived Under Chemically Defined Animal Product-Free Low Oxygen Conditions are Rich in MSCA-1
            <sup>+</sup>
            Subpopulation

Devito, Liani; Badraiq, Heba; Galleu, Antonio; Taheem, Dheraj K.; Codognotto, Stefano; Siow, Richard; Briley, Annette; Shennan, Andrew; Poston, Lucilla; McGrath, John A.; Gentleman, Eileen; Dazzi, Francesco; Ilić, Duško

doi:10.2217/rme.14.60

Cited by 14 publications

(19 citation statements)

References 35 publications

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“…Growing evidence indicate similar or superior proliferative capacity as well as maintenance of three-lineage differentiation ability and surface antigen expression of MSCs cultured in xeno-free media compared to standard serum-based conditions [18–21], which was further supported by our results. However, the potential impact of such xeno-free media on the properties of MSC-EVs has not been studied.…”

Section: Discussionsupporting

confidence: 86%

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Diverse impact of xeno-free conditions on biological and regenerative properties of hUC-MSCs and their extracellular vesicles

et al. 2016

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Growing evidence indicates that intracellular signaling mediated by extracellular vesicles (EVs) released by stem cells plays a considerable role in triggering the regenerative program upon transplantation. EVs from umbilical cord mesenchymal stem cells (UC-MSC-EVs) have been shown to enhance tissue repair in animal models. However, translating such results into clinical practice requires optimized EV collection procedures devoid of animal-originating agents. Thus, in this study, we analyzed the influence of xeno-free expansion media on biological properties of UC-MSCs and UC-MSC-EVs for future applications in cardiac repair in humans. Our results show that proliferation, differentiation, phenotype stability, and cytokine secretion by UC-MSCs vary depending on the type of xeno-free media. Importantly, we found distinct molecular and functional properties of xeno-free UC-MSC-EVs including enhanced cardiomyogenic and angiogenic potential impacting on target cells, which may be explained by elevated concentration of several pro-cardiogenic and pro-angiogenic microRNA (miRNAs) present in the EVs. Our data also suggest predominantly low immunogenic capacity of certain xeno-free UC-MSC-EVs reflected by their inhibitory effect on proliferation of immune cells in vitro. Summarizing, conscious selection of cell culture conditions is required to harvest UC-MSC-EVs with the optimal desired properties including enhanced cardiac and angiogenic capacity, suitable for tissue regeneration.Key message Type of xeno-free media influences biological properties of UC-MSCs in vitro.Certain xeno-free media promote proliferation and differentiation ability of UC-MSCs.EVs collected from xeno-free cultures of UC-MSCs are biologically active.Xeno-free UC-MSC-EVs enhance cardiac and angiogenic potential of target cells.Type of xeno-free media determines immunomodulatory effects mediated by UC-MSC-EVs. Electronic supplementary materialThe online version of this article (doi:10.1007/s00109-016-1471-7) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 86%

“…Various chemically defined xeno-free media dedicated to support MSCs growth and characteristics have been offered on the market and their ability to maintain MSCs properties has already been confirmed [18–21]. However, the impact of such media on the therapeutic properties of MSCs and MSC-derived EVs has never been studied.…”

Section: Introductionmentioning

confidence: 99%

Diverse impact of xeno-free conditions on biological and regenerative properties of hUC-MSCs and their extracellular vesicles

et al. 2016

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“…The absence of MSCA-1 expression in WJ-MSCs could be associated with oxygen levels used during cell expansion 32 . For example, Devito et al showed a significant increase in the number MSCA-1 + cells within a WJ-MSCs population after in vitro expansion in low oxygen conditions 33 . www.nature.com/scientificreports www.nature.com/scientificreports/ The proliferation rate of MSCs differed depending on the tissue source.…”

Section: Discussionmentioning

confidence: 99%

A Comparative Analysis of Multipotent Mesenchymal Stromal Cells derived from Different Sources, with a Focus on Neuroregenerative Potential

Petrenko

Vacková

Kekulová

et al. 2020

Sci Rep

134

109

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Multipotent mesenchymal stromal cells (MScs) can be considered an accessible therapeutic tool for regenerative medicine. Here, we compared the growth kinetics, immunophenotypic and immunomodulatory properties, gene expression and secretome profile of MSCs derived from human adult bone marrow (BM-MSCs), adipose tissue (AT-MSCs) and Wharton's jelly (WJ-MSCs) cultured in clinically-relevant conditions, with the focus on the neuroregenerative potential. All the cell types were positive for CD10/CD29/CD44/CD73/CD90/CD105/HLA-ABC and negative for CD14/CD45/CD235a/ CD271/HLA-DR/VEGFR2 markers, but they differed in the expression of CD34/CD133/CD146/SSEA-4/ MSCA-1/CD271/HLA-DR markers. BM-MSCs displayed the highest immunomodulatory activity compared to AT-and WJ-MSCs. On the other hand, BM-MSCs secreted the lower content and had the lower gene expression of neurotrophic growth factors compared to other cell lines, which may be caused by the higher sensitivity of BM-MSCs to nutrient limitations. Despite the differences in growth factor secretion, the MSC secretome derived from all cell sources had a pronounced neurotrophic potential to stimulate the neurite outgrowth of DRG-neurons and reduce the cell death of neural stem/progenitor cells after H 2 o 2 treatment. Overall, our study provides important information for the transfer of basic MSC research towards clinical-grade manufacturing and therapeutic applications.

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“…MSCs were isolated at research laboratory grade standards. Briefly, cords were collected in PBS containing 40μg/ml of gentamicin [34]. Cords were cut into sections to expose the WJ, which was minced into fine pieces (1-3 mm 2 ).…”

Section: Hepatocyte and Msc Isolationmentioning

confidence: 99%

Methylcellulose as a scaffold in the culture of liver-organoids for the potential of treating acute liver failure

Chandrashekran

Mitry

Prema-chandra

et al. 2018

Cell Gene Therapy Insights

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Much progress has been made in understanding the development of human organs through advanced cellular and molecular techniques. Acute liver failure (ALF) in children is a life-threatening condition that relies on liver or hepatocyte transplantation. The translation of novel regenerative medicine strategies for the treatment of ALF is however somewhat limited. Here, we show that in vitro liver-organoids derived from human umbilical cord derived mesenchymal stem cells and human cadaveric donor-derived hepatocytes, cultured in a clinically appropriate manner, exhibit liver function. We obtained organoids that varied in size and morphology which produced albumin, and detoxified ammonium chloride into urea. Immunohistochemistry of these organoids revealed hepatocyte specific, non-parenchymal markers and histological organisation. Our in vitro findings indicate that these organoids may be a useful bridge in ALF while awaiting liver recovery or transplant. The organoid culture system we have established here is also well suited to drug screening and disease modeling.

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Wharton’s Jelly Mesenchymal Stromal/Stem Cells Derived Under Chemically Defined Animal Product-Free Low Oxygen Conditions are Rich in MSCA-1 ⁺ Subpopulation

Abstract: Easy accessibility, abundance and genetic 'naivety' make WJ MSCs logistically a more attractive source for clinical applications than BM MSCs.

Cited by 14 publications

References 35 publications

Diverse impact of xeno-free conditions on biological and regenerative properties of hUC-MSCs and their extracellular vesicles

Diverse impact of xeno-free conditions on biological and regenerative properties of hUC-MSCs and their extracellular vesicles

A Comparative Analysis of Multipotent Mesenchymal Stromal Cells derived from Different Sources, with a Focus on Neuroregenerative Potential

Methylcellulose as a scaffold in the culture of liver-organoids for the potential of treating acute liver failure

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Wharton’s Jelly Mesenchymal Stromal/Stem Cells Derived Under Chemically Defined Animal Product-Free Low Oxygen Conditions are Rich in MSCA-1 + Subpopulation

Abstract: Easy accessibility, abundance and genetic 'naivety' make WJ MSCs logistically a more attractive source for clinical applications than BM MSCs.

Cited by 14 publications

References 35 publications

Diverse impact of xeno-free conditions on biological and regenerative properties of hUC-MSCs and their extracellular vesicles

Diverse impact of xeno-free conditions on biological and regenerative properties of hUC-MSCs and their extracellular vesicles

A Comparative Analysis of Multipotent Mesenchymal Stromal Cells derived from Different Sources, with a Focus on Neuroregenerative Potential

Methylcellulose as a scaffold in the culture of liver-organoids for the potential of treating acute liver failure

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Product

Resources

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Wharton’s Jelly Mesenchymal Stromal/Stem Cells Derived Under Chemically Defined Animal Product-Free Low Oxygen Conditions are Rich in MSCA-1 ⁺ Subpopulation