Mesenchymal Stromal Cells Engineered to Produce IGF-I by Recombinant Adenovirus Ameliorate Liver Fibrosis in Mice

Fiore, Esteban; BayoJuan, M; GarciaMariana, G; MalviciniMariana,; LloydRodrigo,; PiccioniFlavia,; RizzoManglio,; PeixotoEstanislao,; Beatriz, SolaM.; AtorrasagastiCatalina,; Alaniz, Laura; Camilletti, María Andrea; EnguitaMónica,; PrietoJesús,; Aquino, Jorge B.; MazzoliniGuillermo,

doi:10.1089/scd.2014.0174

Cited by 66 publications

(59 citation statements)

References 26 publications

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“…Furthermore, our own results suggest that an upregulation in the expression of HGF and/or IGF-1 by MSCs, as well as their de novo expression by hepatocytes, early after MSCs transplantation, are likely involved in their therapeutic effect [76] (Fig. 2).…”

Section: Mechanisms Involved In Msc-mediated Liver Fibrosis/cirrhosismentioning

confidence: 82%

“…In different liver fibrosis/cirrhosis in vivo models, abundant highly autofluorescent ceroid-ladden macrophage cells are found in proximity to portal areas and fibrotic bridges [74,75], which makes difficult to truly identify cells under the fluorescence microscope. By mean of chromogenic immunostaining techniques and using green fluorescent protein (GFP) as marker we were able to show that significant numbers of MSCs are present within liver fibrotic parenchyma at least during the first 7 days after their systemic application [76].…”

Section: In Vivo Trackingmentioning

confidence: 99%

“…Thus, crucial events triggered by MSCs might be induced early after their application in vivo. In fact, we have recently shown that as soon as 1 day after MSCs systemic application a peak in insulin growth factor like-I (IGF-I) and hepatocyte growth factor (HGF) is observed in the fibrotic liver, subsequently followed by a significant downregulation of transforming growth factor-beta 1 (TGF-β1), alpha smooth muscle actin (α-SMA) and pro-collagen 1A2 expression levels [76] (Fig. 2).…”

Section: Mechanisms Involved In Msc-mediated Liver Fibrosis/cirrhosismentioning

confidence: 99%

“…2). From those studies multiple mechanisms have been suggested to play a role in in vivo liver amelioration [97], such as: immunomodulation [56,98] (as discussed above); apoptosis of HeSCs [99]; inhibition of HeSC activation and/or their deactivation [76,100]; protective effects on hepatic cells [100][101][102][103] (see above), and restoration or induction of hepatic cell proliferation [76,84,103,104] (Fig. 2).…”

Section: Mechanisms Involved In Msc-mediated Liver Fibrosis/cirrhosismentioning

confidence: 99%

“…2). Finally and considering that IGF-I expression levels are downregulated in a fibrotic liver [113], it is worth noting that by applying multiple doses of IGF-I-transduced MSCs in the context of liver fibrosis into immunocompetent mice we were able to significantly improve the therapeutic effect of a single MSC dose of same treatment [76].…”

Section: Mechanisms Involved In Msc-mediated Liver Fibrosis/cirrhosismentioning

confidence: 99%

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Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives

Fiore

Mazzolini

Aquino

2015

Stem Cell Rev and Rep

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Mesenchymal stem/stromal cells (MSCs) are progenitors which share plastic-adherence capacity and cell surface markers but have different properties according to their cell and tissue sources and to culture conditions applied. Many recent publications suggest that MSCs can differentiate into hepatic-like cells, which can be a consequence of either a positive selection of rare in vivo pluripotent cells or of the original plasticity of some cells contributing to MSC cultures. A possible role of MSCs in hereditary transmission of obesity and/or diabetes as well as properties of MSCs regarding immunomodulation, cell fusion and exosome release capacities are discussed according to recent literature. Limitations in methods used to track MSCs in vivo especially in the context of liver cirrhosis are addressed as well as strategies explored to enhance their migratory, survival and proliferation properties, which are known to be relevant for their future clinical use. Current knowledge regarding mechanisms involved in liver cirrhosis amelioration mediated by naïve and genetically modified MSCs as well as the effects of applying preconditioning and combined strategies to improve their therapeutic effects are evaluated. Finally, first reports of GMP guidelines and biosafety issues in MSCs applications are discussed.

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Section: Mechanisms Involved In Msc-mediated Liver Fibrosis/cirrhosismentioning

confidence: 82%

Section: In Vivo Trackingmentioning

confidence: 99%

Section: Mechanisms Involved In Msc-mediated Liver Fibrosis/cirrhosismentioning

confidence: 99%

Section: Mechanisms Involved In Msc-mediated Liver Fibrosis/cirrhosismentioning

confidence: 99%

Section: Mechanisms Involved In Msc-mediated Liver Fibrosis/cirrhosismentioning

confidence: 99%

See 3 more Smart Citations

Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives

Fiore

Mazzolini

Aquino

2015

Stem Cell Rev and Rep

Self Cite

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Mesenchymal stromal cells as gene delivery vehicles to treat nonmalignant diseases

Beegle

Nolta

Fierro

2016

The Biology and Therapeutic Application of Mesenchymal Cells

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Extracellular vesicles derived from mesenchymal stem/stromal cells: The regenerative impact in liver diseases

et al. 2021

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Liver dysfunctions are classified into acute and chronic diseases, which comprise a heterogeneous group of pathological features and a high mortality rate. Liver transplantation remains the gold‐standard therapy for most liver diseases, with concomitant limitations related to donor organ shortage and lifelong immunosuppressive therapy. A concept in liver therapy intends to overcome these limitations based on the secreted extracellular vesicles (EVs; microvesicles and exosomes) by mesenchymal stem/stromal cells (MSCs). A significant number of studies have shown that factors released by MSCs could induce liver repair and ameliorate systemic inflammation through paracrine effects. It is well known that this paracrine action is based not only on the secretion of cytokines and growth factors but also on EVs, which regulate pathways associated with inflammation, hepatic fibrosis, integrin‐linked protein kinase signaling, and apoptosis. Herein, we extensively discuss the differential effects of MSC‐EVs on different liver diseases and on cellular and animal models and address the complex molecular mechanisms involved in the therapeutic potential of EVs. In addition, we cover the crucial information regarding the type of molecules contained in MSC‐EVs that can be effective in the context of liver diseases. In conclusion, outcomes on MSC‐EV‐mediated therapy are expected to lead to an innovative, cell‐free, noninvasive, less immunogenic, and nontoxic alternative strategy for liver treatment and to provide important mechanistic information on the reparative function of liver cells.

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Mesenchymal Stromal Cells Engineered to Produce IGF-I by Recombinant Adenovirus Ameliorate Liver Fibrosis in Mice

Cited by 66 publications

References 26 publications

Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives

Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives

Mesenchymal stromal cells as gene delivery vehicles to treat nonmalignant diseases

Extracellular vesicles derived from mesenchymal stem/stromal cells: The regenerative impact in liver diseases

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