Serum-Free Media and the Immunoregulatory Properties of Mesenchymal Stem CellsIn VivoandIn Vitro

Wu, Mei; Han, Zhibo; Liu, Jun Feng; Wang, You Wei; Zhang, Jianzhong; Li, Chun Tuan; Xin, Peng Liang; Han, Zhong Chao; Zhu, Xiong Peng

doi:10.1159/000358635

Cited by 27 publications

(19 citation statements)

References 37 publications

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“…The result suggests that direct contact between ASCs and PBMCs inhibits the secretion of IFN-g and TNFa. Wu et al [55] reported a similar phenomenon of reduced IFN-g and TNF-a secretion of CD4 + T cells after coculture with MSCs. In their study, T cells were activated for higher IFN-g and TNF-a secretion by PHA/IL-2 exposure, and reduced secretion of these factors was observed after coculture with MSCs.…”

Section: Discussionmentioning

confidence: 73%

Different Culture Conditions Modulate the Immunological Properties of Adipose Stem Cells

Patrikoski

Sivula

Huhtala

et al. 2014

Stem Cells Translational Medicine

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The potential of human adipose stem cells (ASCs) for regenerative medicine has received recognition owing to their ease of isolation and their multilineage differentiation capacity. Additionally, low immunogenicity and immunosuppressive properties make them a relevant cell source when considering immunomodulation therapies and allogeneic stem cell treatments. In the current study, immunogenicity and immunosuppression of ASCs were determined through mixed lymphocyte reactions. The immunogenic response was analyzed after cell isolation and expansion in fetal bovine serum (FBS), human serum (HS)-supplemented medium, and xeno-free and serum-free (XF/SF) conditions. Additionally, the immunophenotype and the secretion of CXC chemokine ligand 8 (CXCL8), CXCL9, CXCL10, C-C chemokine ligand 2 (CCL2), CCL5, interleukin 2 (IL-2), IL-4, IL-6, IL-10, IL-17A, tumor necrosis factora, interferon-g, transforming growth factor-b1, indoleamine 2,3-deoxygenase, Galectin-1, and Galectin-3 were analyzed. The results showed that ASCs were weakly immunogenic when expanded in any of the three conditions. The significantly strongest suppression was observed with cells expanded in FBS conditions, whereas higher ASC numbers were required to display suppression in HS or XF/SF conditions. In addition, statistically significant differences in protein secretion were observed between direct versus indirect cocultures and between different culture conditions. The characteristic immunophenotype of ASCs was maintained in all conditions. However, in XF/SF conditions, a significantly lower expression of CD54 (intercellular adhesion molecule 1) and a higher expression of CD45 (lymphocyte common antigen) was observed at a low passage number. Although culture conditions have an effect on the immunogenicity, immunosuppression, and protein secretion profile of ASCs, our findings demonstrated that ASCs have low immunogenicity and promising immunosuppressive potential whether cultured in FBS, HS, or XF/SF conditions. STEM CELLS TRANSLATIONAL

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Section: Discussionmentioning

confidence: 73%

Different Culture Conditions Modulate the Immunological Properties of Adipose Stem Cells

Patrikoski

Sivula

Huhtala

et al. 2014

Stem Cells Translational Medicine

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“…Mesenchymal stem cells (MSCs) are undifferentiated and multipotent adult stem cells that are mainly collected from the bone marrow, adipose tissue, and umbilical cord blood . MSCs have been used in various experimental models of diseases . Initially, the reparative and regenerative effects of MSCs were determined by their ability to be engrafted into various injured tissues .…”

Section: Introductionmentioning

confidence: 99%

Serum-Free Medium Enhances the Immunosuppressive and Antifibrotic Abilities of Mesenchymal Stem Cells Utilized in Experimental Renal Fibrosis

Yoshida

Nakashima

Doi

et al. 2018

Stem Cells Translational Medicine

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Serum used in culture medium brings risks of immune reactions or infections and thus may hinder using ex vivo expanded mesenchymal stem cells (MSCs) for medical treatment. Here, we cultured MSCs in a serum‐free medium (SF‐MSCs) and in a medium containing 10% fetal bovine serum (10%MSCs) and investigated their effects on inflammation and fibrosis. MSC‐conditioned medium suppressed transforming growth factor‐β1–induced phosphorylation of Smad2 in HK‐2 cells, with no significant difference between the two MSCs. This finding suggests that the direct antifibrotic effect of SF‐MSCs is similar to that of 10%MSCs. However, immunohistochemistry revealed that renal fibrosis induced by unilateral ureteral obstruction in rats was more significantly ameliorated by the administration of SF‐MSCs than by that of 10%MSCs. Coculture of MSCs and monocytic THP‐1 cell‐derived macrophages using a Transwell system showed that SF‐MSCs significantly induced polarization from the proinflammatory M1 to the immunosuppressive M2 phenotype macrophages, suggesting that SF‐MSCs strongly suppress the persistence of inflammation. Furthermore, the gene expression of tumor necrosis factor‐α–induced protein 6 (TSG‐6), which inhibits the recruitment of inflammatory cells, was higher in SF‐MSCs than in 10%MSCs, and TSG‐6 knockdown in SF‐MSCs attenuated the anti‐inflammatory responses in unilateral ureteral obstruction rats. These findings imply that SF culture conditions can enhance the immunosuppressive and antifibrotic abilities of MSCs and the administration of ex vivo expanded SF‐MSCs has the potential to be a useful therapy for preventing the progression of renal fibrosis. Stem Cells Translational Medicine 2018;7:893–905

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“…Mesenchymal stem cells (MSCs) are a population of self-renewing multipotent cells that have significant clinical potential in cellular therapies for tissue regeneration [4,5].…”

Section: Introductionmentioning

confidence: 99%

MiR-214 Attenuates Osteogenic Differentiation of Mesenchymal Stem Cells via Targeting FGFR1

Yang

Ge²,

Cao³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Postmenopausal osteoporosis is closely associated with reduction in the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. Previous studies have demonstrated that miR-214 plays an important role in the genesis and development of postmenopausal osteoporosis. Here, we performed this study to investigate the potential mechanism by which miR-214 regulates osteoblast differentiation of MSCs. Methods: First, we explored the expression of miR-214 in MSCs of osteoporotic mice. Next, we examined the change of miR-214 during osteoblast differentiation of MSCs. Then, MSCs were infected with lentiviral vectors expressing miR-214 or miR-214 sponge to investigate the effect of miR-214 on osteoblast differentiation of MSCs. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-214. Results: MiR-214 was up-regulated in MSCs of osteoporotic mice and down-regulated during osteoblast differentiation of MSCs. Furthermore, overexpression of miR-214 inhibited osteoblast differentiation of MSCs in vitro, whereas inhibition of miR-214 function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that FGFR1 is a direct target of miR-214. Conclusions: MiR-214 attenuates osteogenesis by inhibiting the FGFR1/FGF signaling pathway. Our findings suggest that targeting miR-214 promises to be a potential therapy in treatment of postmenopausal osteoporosis.L. Yang and D. Ge contributed to the work equally.

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Serum-Free Media and the Immunoregulatory Properties of Mesenchymal Stem CellsIn VivoandIn Vitro

Cited by 27 publications

References 37 publications

Different Culture Conditions Modulate the Immunological Properties of Adipose Stem Cells

Different Culture Conditions Modulate the Immunological Properties of Adipose Stem Cells

Serum-Free Medium Enhances the Immunosuppressive and Antifibrotic Abilities of Mesenchymal Stem Cells Utilized in Experimental Renal Fibrosis

MiR-214 Attenuates Osteogenic Differentiation of Mesenchymal Stem Cells via Targeting FGFR1

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