3D Spheroid Culture Enhances the Expression of Antifibrotic Factors in Human Adipose-Derived MSCs and Improves Their Therapeutic Effects on Hepatic Fibrosis

Zhang, Xuan; Hu, Minggen; Pan, Ke; Li, Chonghui; Liu, Rong

doi:10.1155/2016/4626073

Cited by 37 publications

(37 citation statements)

References 31 publications

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“…The MSCs cultured in 3D were found to secrete higher levels of antifibrotic factors like insulin growth factor 1 (IGF-1) and interleukin-6 (IL-6), which are helpful in treating fibrosis. (19) Similarly, MSCs cultured in 3D spheroids instead of 2D monolayer cultures were found to survive better and display improved therapeutic effects when injected in sites of acute kidney injury. (20) In addition, Gaedtke et al performed proteome analysis on low-passage colon carcinoma cells cultured as multicellular spheroids versus monolayers, and identifies differences in protein expression levels relevant to tumor cell proliferation, survival, and chemoresistance.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Proteomic and Phosphoproteomic Comparison of 2D and 3D Colon Cancer Cell Culture Models

et al. 2016

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Cell cultures are widely used model systems. Some immortalized cell lines can be grown in either two-dimensional (2D) adherent monolayers or in three-dimensional (3D) multicellular aggregates, or spheroids. Here, the quantitative proteome and phosphoproteome of colon carcinoma HT29 cells cultures in 2D monolayers and 3D spheroids were compared with a stable isotope labeling of amino acids (SILAC) labeling strategy. Two biological replicates from each sample were examined and notable differences in both the proteome and the phosphoproteome were determined by nano-liquid chromatography tandem mass spectrometry (nLC-MS/MS) to assess how growth configuration affects molecular expression. A total of 5867 protein groups, including 2523 phosphoprotein groups and 8733 phosphopeptides were identified in the samples. The Gene Ontology analysis revealed enriched GO terms in the 3D samples for RNA binding, nucleic acid binding, enzyme binding, cytoskeletal protein binding, and histone binding for their molecular functions (MF) and in the process of cell cycle, cytoskeleton organization, and DNA metabolic process for the biological process (BP). The KEGG pathway analysis indicated that 3D cultures are enriched for oxidative phosphorylation pathways, metabolic pathways, peroxisome pathways, and biosynthesis of amino acids. In contrast, analysis of the phosphoproteomes indicated that 3D cultures have decreased phosphorylation correlating with slower growth rates and lower cell-to extracellular matrix interactions. In sum, these results provide quantitative assessments of the effects on the proteome and phosphoproteome of culturing cells in 2D versus 3D cell culture configurations.

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Section: Introductionmentioning

confidence: 99%

Quantitative Proteomic and Phosphoproteomic Comparison of 2D and 3D Colon Cancer Cell Culture Models

et al. 2016

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“…Several studies, including one in four patients with cirrhosis, have shown that ASC can reduce alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin while increasing albumin and maintaining prothrombin activity (Fig. D) . This may be due to the ability of ASC to reduce liver fibrosis through reduced inflammation, reduced apoptosis, and improved hepatocyte regeneration .…”

Section: Resultsmentioning

confidence: 98%

“…D) . This may be due to the ability of ASC to reduce liver fibrosis through reduced inflammation, reduced apoptosis, and improved hepatocyte regeneration . In the Phase I clinical study of four patients with cirrhosis, safety of intra‐arterial infusion of ASC into the common hepatic artery was analyzed .…”

Section: Resultsmentioning

confidence: 99%

“…Several studies have shown differentiation to repair damaged tissues directly . However, most of the therapeutic efficacy of SVF and ASCs likely is likely a consequence of paracrine effects, as demonstrated by studies showing effects in the absence of direct cell migration to the target tissue, alterations in gene expression in transwell experiments, and effects of ASC‐conditioned media and exosomes . In addition to paracrine effects, ASC possess the capacity to home to sites of neurological tumors and provide local targeted therapy while reducing systemic exposure to drugs such as chemotherapy .…”

Section: Discussionmentioning

confidence: 99%

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Concise Review: Using Fat to Fight Disease: A Systematic Review of Nonhomologous Adipose-Derived Stromal/Stem Cell Therapies

et al. 2018

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The objective of this Review is to describe the safety and efficacy of adipose stem/stromal cells (ASC) and stromal vascular fraction (SVF) in treating common diseases and the next steps in research that must occur prior to clinical use. Pubmed, Ovid Medline, Embase, Web of Science, and the Cochrane Library were searched for articles about use of SVF or ASC for disease therapy published between 2012 and 2017. One meta-analysis, 2 randomized controlled trials, and 16 case series were included, representing 844 human patients. Sixty-nine studies were performed in preclinical models of disease. ASCs improved symptoms, fistula healing, remission, and recurrence rates in severe cases of inflammatory bowel disease. In osteoarthritis, ASC and SVF improved symptom-related, functional, radiographic, and histological scores. ASC and SVF were also shown to improve clinical outcomes in ischemic stroke, multiple sclerosis, myocardial ischemia, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, chronic liver failure, glioblastoma, acute kidney injury, and chronic skin wounds. These effects were primarily paracrine in nature and mediated through reduction of inflammation and promotion of tissue repair. In the majority of human studies, autologous ASC and SVF from liposuction procedures were used, minimizing the risk to recipients. Very few serious, treatment-related adverse events were reported. The main adverse event was postprocedural pain. SVF and ASC are promising therapies for a variety of human diseases, particularly for patients with severe cases refractory to current medical treatments. Further randomized controlled trials must be performed to elaborate potential safety and efficacy prior to clinical use. Stem Cells 2018;36:1311-1328.

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“…While 3D culture could restore the expression of these receptors, which were critical for MSCs homing to the injury site 30 , 31 . The 3D MSCs have been reported to be beneficial for liver fibrosis and hepatitis 32 , 33 , but their effect on hepatic IRI remains largely unknown. Different kind of MSCs exhibits different immunobiological properties, among which umbilical cord lining MSCs (UC-MSCs) have especially low immunogenicity compared with other extraembryonic tissue–derived MSCs 34 .…”

Section: Introductionmentioning

confidence: 99%

Spheroid-cultured human umbilical cord-derived mesenchymal stem cells attenuate hepatic ischemia-reperfusion injury in rats

Sun

Wang

Zhou

et al. 2018

Sci Rep

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Mesenchymal stem cell (MSC) transplantation is a promising treatment for ischemia-reperfusion injury (IRI). However, its effects on hepatic IRI were not consistent in the previous studies. 3D spheroid-cultured MSCs enhance their production of trophic and anti-inflammatory properties, but their effects on hepatic IRI remain unclear. In this study, we compared the 3D spheroid-cultured human umbilical derived MSCs (3D UC-MSCs) with 2D-cultured UC-MSCs (2D UC-MSCs) on treating hepatic IRI. The RNA sequencing data showed that suppression of cell mitosis, response to hypoxia, inflammation, and angiogenesis were the top genetic changes in 3D UC-MSCs compared with 2D UC-MSCs. Although both pro-inflammatory and anti-inflammatory genes were upregulated in the 3D UC-MSCs, the mRNA and protein of an RNase (ZC3H12A), which turnovers the mRNA of pro-inflammatory genes at the post-transcript level, were significantly upregulated in 3D UC-MSCs. 3D UC-MSCs reduced the secretion of many chemokines and growth factors, but increased the secretion of vascular endothelial growth factor. Compared with the vehicle and 2D UC-MSCs, 3D UC-MSCs significantly reduced hepatic IRI in rats, based on the plasma aminotransferase levels, liver damage scores, neutrophil infiltration, hepatocyte apoptosis and expression of inflammation-associated genes. These findings suggest that 3D UC-MSCs therapy is a promising treatment for hepatic IRI.

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3D Spheroid Culture Enhances the Expression of Antifibrotic Factors in Human Adipose-Derived MSCs and Improves Their Therapeutic Effects on Hepatic Fibrosis

Cited by 37 publications

References 31 publications

Quantitative Proteomic and Phosphoproteomic Comparison of 2D and 3D Colon Cancer Cell Culture Models

Quantitative Proteomic and Phosphoproteomic Comparison of 2D and 3D Colon Cancer Cell Culture Models

Concise Review: Using Fat to Fight Disease: A Systematic Review of Nonhomologous Adipose-Derived Stromal/Stem Cell Therapies

Spheroid-cultured human umbilical cord-derived mesenchymal stem cells attenuate hepatic ischemia-reperfusion injury in rats

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