Dataset Information

The Impact of Cell-Expansion and Inflammation on The Immune-Biology of Human Adipose Tissue-Derived Mesenchymal Stromal Cells.

ABSTRACT: Background: As a cell-based therapeutic, AT-MSCs need to create an immuno-reparativeenvironment appropriate for tissue repair. In the presence of injury, MSCs may have to proliferate and face inflammation. Clinical application requires repeated administrations of a high number of cellswith a well-established immune profile. Methods: We have established an immuno-comparative screening by determining the expression of 28 molecules implicated in immune regulation. This screening was performed during cell-expansion and inflammatory priming of AT-MSCs. Results: Our study confirms that AT-MSCs are highly expandable and sensitive to inflammation. Both conditions have substantially modulated the expression of a panel of immunological marker. Specifically, CD34 expression was substantially decreased upon cell-passaging. HLA-ABC, CD40 CD54, CD106, CD274 and CD112 were significantly increased by inflammation. In vitro cell-expansion also significantly altered the expression profile of HLA-DR, CD40, CD62L, CD106, CD166, HLA-G, CD200, HO-1, CD155 and ULBP-3. Conclusion: This study points out the response and characteristics of MSCs following expansion and inflammatory priming. It will strength our knowledge about the molecular mechanisms that may improve or hamper the therapeutic potential of MSCs. These immunological changes need to be further characterized to guarantee a safe cellular product with consistent quality and high therapeutic efficacy.

SUBMITTER: Buyl K

PROVIDER: S-EPMC7141238 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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The Impact of Cell-Expansion and Inflammation on The Immune-Biology of Human Adipose Tissue-Derived Mesenchymal Stromal Cells.

Buyl Karolien K Merimi Makram M Rodrigues Robim M RM Moussa Agha Douâa D Melki Rahma R Vanhaecke Tamara T Bron Dominique D Lewalle Philippe P Meuleman Nathalie N Fahmi Hassan H Rogiers Vera V Lagneaux Laurence L De Kock Joery J Najar Mehdi M

Journal of clinical medicine 20200304 3

<b>Background</b>: As a cell-based therapeutic, AT-MSCs need to create an immuno-reparativeenvironment appropriate for tissue repair. In the presence of injury, MSCs may have to proliferate and face inflammation. Clinical application requires repeated administrations of a high number of cellswith a well-established immune profile. <b>Methods</b>: We have established an immuno-comparative screening by determining the expression of 28 molecules implicated in immune regulation. This screening was p ...[more]

PMID: 32143473

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Project description:ObjectiveRecent advances in cell therapy have encouraged researchers to provide an alternative for treatment and restoration of damaged liver through using hepatocytes. However, these cells quickly lose their functional capabilities in vitro. Here, we aim to use the secretome of mesenchymal stromal cells (MSCs) to improve in vitro maintenance conditions for hepatocytes.Materials and methodsIn this experimental study, following serum deprivation, human adipose tissue-derived MSCs (hAT-MSCs) were cultured for 24 hours under normoxic (N) and hypoxic (H) conditions. Their conditioned media (CM) were subsequently collected and labeled as N-CM (normoxia) and H-CM (hypoxia). Murine hepatocytes were isolated by perfusion of mouse liver with collagenase, and were cultured in hepatocyte basal (William's) medium supplemented with 4% N-CM or H-CM. Untreated William's and hepatocyte-specific media (HepZYM) were used as controls. Finally, we evaluated the survival and proliferation rates, as well as functionality and hepatocyte-specific gene expressions of the cells.ResultsWe observed a significant increase in viability of hepatocytes in the presence of N-CM and H-CM compared to HepZYM on day 5, as indicated by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)- 2H-tetrazolium) assay. Indocyanine green (ICG) uptake of hepatocytes in the H-CM and HepZYM groups on days 3 and 5 also suggested that H-CM maintained the hepatocytes at about the same level as the hepatocyte-specific medium. The HepZYM group had significantly higher levels of albumin (Alb) and urea secretion compared to the other groups (P<0.0001). However, there were no significant differences in cytochrome activity and cytochrome gene expression profiles among these groups. Finally, we found a slightly, but not significantly higher concentration of vascular endothelial growth factor (VEGF) in the H-CM group compared to the N-CM group (P=0.063).ConclusionThe enrichment of William's basal medium with 4% hAT-MSC-H-CM improved some physiologic parameters in a primary hepatocyte culture.

Dataset Information

The Impact of Cell-Expansion and Inflammation on The Immune-Biology of Human Adipose Tissue-Derived Mesenchymal Stromal Cells.

Publications

The Impact of Cell-Expansion and Inflammation on The Immune-Biology of Human Adipose Tissue-Derived Mesenchymal Stromal Cells.

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