The role of extracellular matrix on liver stem cell fate: A dynamic relationship in health and disease

Sánchez-Romero, Natalia; Sainz‐Arnal, Pilar; Plá-Palacín, Iris; Dachary, Pablo Royo; Almeida, Helen; Pastor, C.; Soto, Daniela Rubio; Rodriguez, Milagros Chico; Arbizu, Emma Olmedo; Martinez, Lourdes Bengochea; Serrano-Aulló, Trinidad; Baptista, Pedro M.

doi:10.1016/j.diff.2019.03.001

Cited by 15 publications

(11 citation statements)

References 95 publications

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“…The implantation of MSCs especially combined with biodegradable materials for tissue engineering applications such as collagen [ 6 , 7 ]. It is a major extracellular matrix (ECM) component that has been widely used for constructive remodeling to facilitate cell growth and differentiation [ 8 ].…”

Section: Resultsmentioning

confidence: 99%

A review and update for registered clinical studies of stem cells for non-tumorous and non-hematological diseases

Chen

Luo

Tian

et al. 2021

Regenerative Therapy

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Objective To provide consultative information on selecting potential indications of stem cells in the treatment of non-tumorous and non-hematopoietic system conditions, we screened the clinical trials on website: http://www.clinicaltrials.gov . Methods A literature search was conducted using the National Institute of Health (NIH) website ( http://www.clinicaltrials.gov ) from May 10th, 2012 to Oct 13th, 2020 with stem cells as an intervention in human trials for non-tumorous and non-hematological conditions. There was no restriction for language, research location, and research race. Results and conclusion Search terms initially found a total of 3576 articles. Firstly, 138 terminated or suspended studies were excluded and further 24 repeated studies were excluded. Secondly, 987 tumorous and hematopoietic conditions-related studies were excluded. Lastly, 1218 studies were excluded without stem cell therapy as their primary purpose. A total of 1209 research studies were entered into the analysis and reviewed. The top 4 diseases were about motor system diseases 229 (19.28%). In addition, 206 (17.34%) studies were related to central nervous system (CNS) diseases. 140 (11.78%) were autoimmune diseases or graft-versus-host disease (GVHD) after organ transplantation. 129 (10.86%) were about respiratory system diseases, among them, 44.19% projects were about new coronary pneumonia (NCP). The main cell types used in various diseases are Mesenchymal Stem Cells (MSCs), bone marrow stem cells (BM-SCs), peripheral blood stem cells (PBSCs), hematopoietic stem cells (HSCs), adipose stem cell (ASCs) and precursor cells.

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Section: Resultsmentioning

confidence: 99%

A review and update for registered clinical studies of stem cells for non-tumorous and non-hematological diseases

Chen

Luo

Tian

et al. 2021

Regenerative Therapy

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“…Previous studies have shown that tissue-engineered livers are an attractive organ replacement solution for compensating the shortage of liver sources. Transplanting cells into a liver matrix made up of a decellularized scaffold that mimics the microstructure of native tissues is expected to provide a functional bionic liver [21][22][23][24][25][26][27]. Our study demonstrated that detergent perfusion through the portal vein created a translucent liver matrix while maintaining the native vasculature for adequate perfusion of constructs that were able to withstand physiological blood pressures.…”

Section: Discussionmentioning

confidence: 96%

Syndecan-4 promotes vascular beds formation in tissue engineered liver via thrombospondin 1

Chen

Huang

et al. 2020

Bioengineered

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Instantaneous blood coagulation after bioengineered liver transplantation is a major issue, and the key process in its prevention is the construction of the endothelial vascular bed on biomimetic scaffolds. However, the specific molecules involved in the regulation of the vascular bed formation remain unclear. Syndecan-4 is a type I transmembrane glycoprotein commonly expressed in the human body; its receptor has been reported as critical for optimal cell adhesion and initiation of intracellular signaling, indicating its promising application in vascular bed formation. In the current study, bioinformatics analysis and in vitro experiments were performed to evaluate whether syndecan-4 promoted endothelial cell migration and functional activation. Exogenous syndecan-4-overexpressing endothelial cells were perfused into the decellularized liver scaffold, which was assessed by Masson's trichrome staining. Western blotting and qRT-PCR were used to evaluate the effects of syndecan-4 on the thrombospondin 1 (THBS1) stability. We found that syndecan-4 promoted the adhesion of vascular endothelial cells and facilitated cell migration and angiogenesis. Furthermore, syndecan-4 overexpression resulted in a well-aligned endothelium on the decellularized liver scaffolds. Mechanistically, syndecan-4 destabilized THBS1 at the protein level. Therefore, our data revealed that syndecan-4 promoted the biological activity of endothelial cells on the bionic liver vascular bed through THBS1. These findings provide scientific evidences for solving transient blood coagulation after bionic liver transplantation.

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“…It is difficult to represent complex liver regeneration in vivo. In liver injury, hepatic regeneration responds to inflammatory cytokines, such as TNFα and IL-6 produced by Kupffer cells, to reconstitute the liver by rapidly inducing cells to enter the cell cycle [46,47]. Additionally, the absence of liver stem/progenitor cells, which contribute to liver regeneration, reveals the need for reinforcement in further studies [48,49].…”

Section: Discussionmentioning

confidence: 99%

Establishing a 3D In Vitro Hepatic Model Mimicking Physiologically Relevant to In Vivo State

Kang

Sarsenova

Kim

et al. 2021

Cells

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Three-dimensional (3D) bioprinting is a promising technology to establish a 3D in vitro hepatic model that holds great potential in toxicological evaluation. However, in current hepatic models, the central area suffers from hypoxic conditions, resulting in slow and weak metabolism of drugs and toxins. It remains challenging to predict accurate drug effects in current bioprinted hepatic models. Here, we constructed a hexagonal bioprinted hepatic construct and incorporated a spinning condition with continuous media stimuli. Under spinning conditions, HepG2 cells in the bioprinted hepatic construct exhibited enhanced proliferation capacity and functionality compared to those under static conditions. Additionally, the number of spheroids that play a role in boosting drug-induced signals and responses increased in the bioprinted hepatic constructs cultured under spinning conditions. Moreover, HepG2 cells under spinning conditions exhibited intensive TGFβ-induced epithelial-to-mesenchymal transition (EMT) and increased susceptibility to acetaminophen (APAP)-induced hepatotoxicity as well as hepatotoxicity prevention by administration of N-acetylcysteine (NAC). Taken together, the results of our study demonstrate that the spinning condition employed during the generation of bioprinted hepatic constructs enables the recapitulation of liver injury and repair phenomena in particular. This simple but effective culture strategy facilitates bioprinted hepatic constructs to improve in vitro modeling for drug effect evaluation.

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The role of extracellular matrix on liver stem cell fate: A dynamic relationship in health and disease

Cited by 15 publications

References 95 publications

A review and update for registered clinical studies of stem cells for non-tumorous and non-hematological diseases

A review and update for registered clinical studies of stem cells for non-tumorous and non-hematological diseases

Syndecan-4 promotes vascular beds formation in tissue engineered liver via thrombospondin 1

Establishing a 3D In Vitro Hepatic Model Mimicking Physiologically Relevant to In Vivo State

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