Evolving Cell-Based and Cell-Free Clinical Strategies for Treating Severe Human Liver Diseases

Cernigliaro, Viviana; Peluso, Rossella; Zedda, Beatrice; Silengo, Lorenzo; Tolosano, Emanuela; Pellicano, Rinaldo; Altruda, Fiorella; Fagoonee, Sharmila

doi:10.3390/cells9020386

Cited by 19 publications

(11 citation statements)

References 121 publications

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“…Tumor cells with a mesenchymal-like phenotype are highly invasion and metastasis, but not all EMTtransformed cells are CSCs. Mesenchymal stem cells exhibit intrinsic therapeutic resistance and maintain their self-renewal ability to form a heterogeneous lineage of tumor cells (26)(27)(28). Previous studies have proposed different biomarkers for the selfrenewal capabilities of HCC (29).…”

Section: Introductionmentioning

confidence: 99%

Association of Preoperative NANOG-Positive Circulating Tumor Cell Levels With Recurrence of Hepatocellular Carcinoma

Yuan

Wang

et al. 2021

Front. Oncol.

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BackgroundCancer stem cells (CSCs) and Circulating tumor cells (CTCs) have been proposed as fundamental causes for the recurrence of hepatocellular carcinoma (HCC). CTCs isolated from patients with HCC illustrate a unique Nanog expression profile analysis. The aim of this study was to enhance the prediction of recurrence and prognosis of the CTC phenotype in patients with HCC by combining Nanog expression into a combined forecasting model.Subjects, Materials, and MethodsWe collected 320 blood samples from 160 patients with HCC cancer before surgery and used CanPatrol™ CTC enrichment technology and in situ hybridization (ISH) to enrich and detect CTCs and CSCs. Nanog expression in all CTCs was also determined. In addition, RT-PCR and immunohistochemistry were used to study the expression of Nanog, E-Cadherin, and N-Cadherin in liver cancer tissues and to conduct clinical correlation studies.ResultsThe numbers of EpCAM mRNA+ CTCs and Nanog mRNA+ CTCs were strongly correlated with postoperative HCC recurrence (CTC number (P = 0.03), the total number of mixed CTCS (P = 0.02), and Nanog> 6.7 (P = 0.001), with Nanog > 6.7 (P = 0.0003, HR = 2.33) being the most crucial marker. There are significant differences in the expression of Nanog on different types of CTC: most Epithelial CTCs do not express Nanog, while most of Mixed CTC and Mesenchymal CTC express Nanog, and their positive rates are 38.7%, 66.7%, and 88.7%, respectively, (P=0.0001). Moreover, both CTC (≤/> 13.3) and Nanog (≤/>6.7) expression were significantly correlated with BCLC stage, vascular invasion, tumor size, and Hbv-DNA (all P < 0.05). In the young group and the old group, patients with higher Nanog expression had a higher recurrence rate. (P < 0.001).ConclusionsThe number of Nanog-positive cells showed positive correlation with the poor prognosis of HCC patients. The detection and analysis of CTC markers (EpCAM and CK8, 18, CD45 Vimentin,Twist and 19) and CSCs markers (NANOG) are of great value in the evaluation of tumor progression.

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Section: Introductionmentioning

confidence: 99%

Association of Preoperative NANOG-Positive Circulating Tumor Cell Levels With Recurrence of Hepatocellular Carcinoma

Yuan

Wang

et al. 2021

Front. Oncol.

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“…MSCs are fibroblast-like cells which show particular characteristics such as adhesion to plastic, expression of surface markers, such as CD90, CD105, CD73, and CD29, and lack of CD34, CD45, and CD79, and multipotency for the possibility to induce these cells to differentiate into osteoblasts, adipocytes and chondroblasts in vitro [ 30 ]. As adult cells, MSCs are genetically stable with respect to induced pluripotent stem cells (iPSCs) and are subject to fewer ethical concerns compared to embryonic stem cells [ 31 ]. MSCs are easily harvested from a large variety of human tissues and cultivated in vitro.…”

Section: Limiting Damage After Corneal Burn Injurymentioning

confidence: 99%

Regenerative Approaches and Future Trends for the Treatment of Corneal Burn Injuries

Saccu

Menchise

Giordano³

et al. 2021

JCM

Self Cite

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Ocular chemical and thermal burns are frequent causes of hospitalization and require immediate interventions and care. Various surgical and pharmacological treatment strategies are employed according to damage severity. Controlling inflammation and neovascularization while promoting normal ocular surface anatomy and function restoration is the principal aim. In the most severe cases, when epithelial healing is severely affected, reconstruction of the ocular surface may be a valid option, which, however, requires expertise, adequate instruments, and qualified donors. Numerous endogenous and exogenous strategies have been considered for corneal repair. Among these, stem cells and their derivatives have offered numerous attractive possibilities in finding an effective way in stimulating corneal regeneration. Limbal epithelial stem cells and mesenchymal cells from the ocular tissue as well as from various sources have demonstrated their effectiveness in dampening neovascularization, scarring, and inflammation, while promoting epithelialization of the injured cornea. Moreover, a plethora of cytokines and growth factors, and extracellular vesicles, which constitute the secretome of these cells, work in concert to enhance wound healing. In this review, we provide an update on the recent potential therapeutic avenues and clinical applications of stem cells and their products in corneal regeneration after burn injury, as well as current imaging strategies for monitoring therapeutic efficacy and damage resolution.

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“…Several studies have found that, under certain culture conditions, MSCs can express hepatocyte-specific genes and metabolic functions, suggesting that MSCs can transdifferentiate into hepatocyte-like cells in vitro. In subsequent years, more evidence was compiled to support this assumption, with many studies confirming the hepatic differentiation potential of MSCs [53][54][55][56][57].…”

Section: Mscs As Hepatocyte-like Cellsmentioning

confidence: 99%

Role of the Microenvironment in Mesenchymal Stem Cell-Based Strategies for Treating Human Liver Diseases

Wang

et al. 2021

Stem Cells International

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Liver disease is a severe health problem that endangers human health worldwide. Mesenchymal stem cell (MSC) therapy is a novel treatment for patients with different liver diseases due to its vast expansion potential and distinctive immunomodulatory properties. Despite several preclinical trials having confirmed the considerable efficacy of MSC therapy in liver diseases, the questionable safety and efficacy still limit its application. As a precursor cell, MSCs can adjust their characteristics in response to the surrounding microenvironment. The microenvironment provides physical and chemical factors essential for stem cell survival, proliferation, and differentiation. However, the mechanisms are still not completely understood. We, therefore, summarized the mechanisms underlying the MSC immune response, especially the interaction between MSCs and the liver microenvironment, discussing how to achieve better therapeutic effects.

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Evolving Cell-Based and Cell-Free Clinical Strategies for Treating Severe Human Liver Diseases

Cited by 19 publications

References 121 publications

Association of Preoperative NANOG-Positive Circulating Tumor Cell Levels With Recurrence of Hepatocellular Carcinoma

Association of Preoperative NANOG-Positive Circulating Tumor Cell Levels With Recurrence of Hepatocellular Carcinoma

Regenerative Approaches and Future Trends for the Treatment of Corneal Burn Injuries

Role of the Microenvironment in Mesenchymal Stem Cell-Based Strategies for Treating Human Liver Diseases

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