Mesenchymal stromal cells isolated from human fetal liver release soluble factors with a potential role in liver tissue repair

Chinnici, Cinzia Maria; Pietrosi, Giada; Iannolo, Gioacchin; Amico, Giandomenico; Cuscino, Nicola; Pagano, Valeria; Conaldi, Pier Giulio

doi:10.1016/j.diff.2018.12.001

Cited by 16 publications

(13 citation statements)

References 53 publications

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“…Immune mediators of liver regeneration that showed a significant increase in expression immediately after the operations were IL-6 and VEGF 17,[42][43][44] . These molecules are known mediators of acute and chronic inflammatory response, carrying out essential functions in repairing tissue injury in all parts of the human body.…”

Section: Discussionmentioning

confidence: 99%

RNA-Seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, ALLPS, and PVL

Çolak

Al‐Harazi

Mustafa

et al. 2020

Sci Rep

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The liver is a unique organ that has a phenomenal capacity to regenerate after injury. Different surgical procedures, including partial hepatectomy (PH), intraoperative portal vein ligation (PVL), and associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) show clinically distinct recovery patterns and regeneration. The observable clinical differences likely mirror some underlying variations in the patterns of gene activation and regeneration pathways. In this study, we provided a comprehensive comparative transcriptomic analysis of gene regulation in regenerating rat livers temporally spaced at 24 h and 96 h after PH, PVL, and ALPPS. The time-dependent factors appear to be the most important determinant of post-injury alterations of gene expression in liver regeneration. Gene expression profile after ALPPS showed more similar expression pattern to the PH than the PVL at the early phase of the regeneration. Early transcriptomic changes and predicted upstream regulators that were found in all three procedures included cell cycle associated genes (E2F1,

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Section: Discussionmentioning

confidence: 99%

RNA-Seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, ALLPS, and PVL

Çolak

Al‐Harazi

Mustafa

et al. 2020

Sci Rep

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“…For CM collection, serum-free alpha-minimum essential medium (MEM) (Gibco, Thermo Fisher Scientific) was added to 80% confluent cells and collected 24 hours later. EVs were isolated by differential ultracentrifugation of CM according to a protocol [ 17 ] and as previously described [ 18 ]. In brief, CM was centrifuged at 1800 × g for 10 minutes to remove cell debris, centrifuged again at 17000 × g for 15 minutes, and then at 160000 × g for 1 hour in the ultracentrifuge (Optima MAX-XP, Beckman Coulter Inc., Irving, TX, USA).…”

Section: Methodsmentioning

confidence: 99%

Small Extracellular Vesicles from Human Fetal Dermal Cells and Their MicroRNA Cargo: KEGG Signaling Pathways Associated with Angiogenesis and Wound Healing

Chinnici

Amico

Gallo

et al. 2020

Stem Cells International

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The use of cell secreted factors in clinical settings could be an alternative to conventional cell therapy, with the advantage of limiting concerns generally associated with traditional cell transplantation, such as tumorigenicity, immunoreactivity, and carrying of infections. Based on our published data, we predict a potential role for extracellular vesicles (EVs) in contributing to the proangiogenic activity of human fetal dermal cell secretome. Depletion of nanosized EVs from secretome significantly impaired its ability to induce formation of mesh-like structures in vitro. The isolated EVs were characterized for size and concentration by nanoparticle tracking analysis, and for protein markers (Rab5+, Alix+, CD63+, and calnexin-). The microRNA profile of EVs revealed 87 microRNAs significantly upregulated (≥15-fold increase) in fetal compared to adult dermal cell-derived EVs. Interestingly, these upregulated microRNAs included microRNAs with a validated role in angiogenesis according to literature. Moreover, the DIANA-TarBase v7.0 analysis confirmed enrichment in the KEGG signaling pathways associated with angiogenesis and wound healing, with the identification of putative target genes including thrombospondin 1. To validate the in silico data, EVs were also characterized for total protein contents. When tested in in vitro angiogenesis, fetal dermal cell-derived EVs were more effective than their adult counterpart in inducing formation of complete mesh-like structures. Furthermore, treatment of fibroblasts with fetal dermal-derived EVs determined a 4-fold increase of thrombospondin 1 protein amounts compared with the untreated fibroblasts. Finally, visualization of CSFE-labeled EVs in the cytosol of target cells suggested a successful uptake of these particles at 4-8 hours of incubation. We conclude that EVs are important contributors of the proangiogenic effect of fetal dermal cell secretome. Hence, EVs could also serve as vehicle for a successful delivery of microRNAs or other molecules of therapeutic interest to target cells.

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“…Liver transplantation or hepatocyte transplantation is currently considered a promising substitute towards therapies for hepatic diseases. However, liver transplantation is crucially limited by shortage in liver donors, high transplantation costs, immune excretion of transplanted cells, and the requirement of long-term immunoinhibition [1]. Mesenchymal stem cells or stem cell derived hepatocytes are favored research subjects due to the fact that they can be easily collected and multiplied in vitro to meet the needs of hepatic function [1].…”

Section: Introductionmentioning

confidence: 99%

“…However, liver transplantation is crucially limited by shortage in liver donors, high transplantation costs, immune excretion of transplanted cells, and the requirement of long-term immunoinhibition [1]. Mesenchymal stem cells or stem cell derived hepatocytes are favored research subjects due to the fact that they can be easily collected and multiplied in vitro to meet the needs of hepatic function [1]. For application of this potential therapy, it is essential to comply with general and reliable protocols to estimate effects of transplantation on homing and differentiation of cells as pre-clinical evaluation [2].…”

Section: Introductionmentioning

confidence: 99%

Efficient Isolation and Long-term Red Fluorescent Nanodia-mond Labeling of Umbilical Cord Mesenchymal Stem Cells for the Effective Differentiation into Hepatocyte-like Cells

Trung

Nguyen

et al. 2020

Braz. arch. biol. technol.

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Fluorescent nanodiamond (FND) has been used for long-term cell labeling and in vivo cell tracking because they have good at photostability and biocompatibility. In this study, we evaluate the effect of fluorescent nanodiamond labeling on in vitro culture and differentiation of human umbilical cord mesenchymal stem cells (hUCMSCs) into hepatocyte-like cells (HLCs). For hepatic differentiation of hUCMSCs, cells were induced with human hepatocyte growth factor, nicotinamide and Dexamethasone. FND was supplied in two experimental groups with 20 μg/mL and 100 μg/mL in 2 hours. The cell was assessed for FND uptake by laser scan microscopy and flow cytometry methods. The effect of FND on hUCMSCs was evaluated by the cell viability and growth assays as well as the differentiation throughout of morphology alterations or gene expression of anfa-fetoprotein, albumin, and hepatocyte nuclear factor 4α. The results showed that the labeling of hUCMSCs is efficient and easy and there was significant cellular uptake of FND. We did not observe any negative impacts of FND to the cell viability and growth. FND can be utilized for the long-term labeling and tracking of hUCSCs and HLCs in vivo studies. HIGHLIGHTS  Fluorescent nanodiamond labeling does not affect the life and growth of hUCMSC.  FND labeling does not affect the hUCMSC differentiation into hepatocyte-like cells.  FND labeling maintain during the procedure of hUCMSC differentiation into hepatocyte-like cells. 2 Do, T.K.; et al.

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Mesenchymal stromal cells isolated from human fetal liver release soluble factors with a potential role in liver tissue repair

Cited by 16 publications

References 53 publications

RNA-Seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, ALLPS, and PVL

RNA-Seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, ALLPS, and PVL

Small Extracellular Vesicles from Human Fetal Dermal Cells and Their MicroRNA Cargo: KEGG Signaling Pathways Associated with Angiogenesis and Wound Healing

Efficient Isolation and Long-term Red Fluorescent Nanodia-mond Labeling of Umbilical Cord Mesenchymal Stem Cells for the Effective Differentiation into Hepatocyte-like Cells

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