scholarly journals Amniotic Epithelial Stem Cells Counteract Acidic Degradation By-Products of Electrospun PLGA Scaffold by Improving Their Immunomodulatory Profile In Vitro

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3221
Author(s):  
Mohammad El Khatib ◽  
Valentina Russo ◽  
Giuseppe Prencipe ◽  
Annunziata Mauro ◽  
Ralf Wyrwa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Average Molecular Weight ◽  
Hydrolytic Degradation ◽  
Considerable Effect ◽  
In Vitro Cytotoxicity ◽  
Epithelial Stem Cells ◽  
Tendon Tissue ◽  
By Products

Electrospun poly(lactic-co-glycolic acid) (PLGA) scaffolds with highly aligned fibers (ha-PLGA) represent promising materials in the field of tendon tissue engineering (TE) due to their characteristics in mimicking fibrous extracellular matrix (ECM) of tendon native tissue. Among these properties, scaffold biodegradability must be controlled allowing its replacement by a neo-formed native tendon tissue in a controlled manner. In this study, ha-PLGA were subjected to hydrolytic degradation up to 20 weeks, under di-H2O and PBS conditions according to ISO 10993-13:2010. These were then characterized for their physical, morphological, and mechanical features. In vitro cytotoxicity tests were conducted on ovine amniotic epithelial stem cells (oAECs), up to 7 days, to assess the effect of non-buffered and buffered PLGA by-products at different concentrations on cell viability and their stimuli on oAECs’ immunomodulatory properties. The ha-PLGA scaffolds degraded slowly as evidenced by a slight decrease in mass loss (14%) and average molecular weight (35%), with estimated degradation half-time of about 40 weeks under di-H2O. The ultrastructure morphology of the scaffolds showed no significant fiber degradation even after 20 weeks, but alteration of fiber alignment was already evident at week 1. Moreover, mechanical properties decreased throughout the degradation times under wet as well as dry PBS conditions. The influence of acid degradation media on oAECs was dose-dependent, with a considerable effect at 7 days’ culture point. This effect was notably reduced by using buffered media. To a certain level, cells were able to compensate the generated inflammation-like microenvironment by upregulating IL-10 gene expression and favoring an anti-inflammatory rather than pro-inflammatory response. These in vitro results are essential to better understand the degradation behavior of ha-PLGA in vivo and the effect of their degradation by-products on affecting cell performance. Indeed, buffering the degradation milieu could represent a promising strategy to balance scaffold degradation. These findings give good hope with reference to the in vivo condition characterized by physiological buffering systems.

In vitro and in vivo differentiation of amniotic epithelial stem cells into hepatocyte-like cells

Placenta ◽  
2011 ◽  
Vol 32 ◽  
pp. S336
Author(s):  
F. Marongiu ◽  
R. Gramignoli ◽  
S. Doratiotto ◽  
M. Serra ◽  
M. Sini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Stem Cells ◽  
In Vivo Differentiation

scholarly journals Lactobacillus rhamnosus GG protects the intestinal epithelium from radiation injury through release of lipoteichoic acid, macrophage activation and the migration of mesenchymal stem cells

Gut ◽  
2018 ◽  
Vol 68 (6) ◽  
pp. 1003-1013 ◽  
Author(s):  
Terrence E Riehl ◽  
David Alvarado ◽  
Xueping Ee ◽  
Aaron Zuckerman ◽  
Lynn Foster ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lamina Propria ◽  
Lactobacillus Rhamnosus ◽  
Lipoteichoic Acid ◽  
Epithelial Stem Cells ◽  
Tlr2 Agonist ◽  
Cox 2

ObjectiveLactobacillus rhamnosus GG (LGG), a probiotic, given by gavage is radioprotective of the mouse intestine. LGG-induced radioprotection is toll-like receptor 2 (TLR2) and cyclooxygenase-2 (COX-2)-dependent and is associated with the migration of COX-2+mesenchymal stem cells (MSCs) from the lamina propria of the villus to the lamina propria near the crypt epithelial stem cells. Our goals were to define the mechanism of LGG radioprotection including identification of the TLR2 agonist, and the mechanism of the MSC migration and to determine the safety and efficacy of this approach in models relevant to clinical radiation therapy.DesignIntestinal radioprotection was modelled in vitro with cell lines and enteroids as well as in vivo by assaying clinical outcomes and crypt survival. Fractionated abdominal and single dose radiation were used along with syngeneic CT26 colon tumour grafts to assess tumour radioprotection.ResultsLGG with a mutation in the processing of lipoteichoic acid (LTA), a TLR2 agonist, was not radioprotective, while LTA agonist and native LGG were. An agonist of CXCR4 blocked LGG-induced MSC migration and LGG-induced radioprotection. LGG given by gavage induced expression of CXCL12, a CXCR4 agonist, in pericryptal macrophages and depletion of macrophages by clodronate liposomes blocked LGG-induced MSC migration and radioprotection. LTA effectively protected the normal intestinal crypt, but not tumours in fractionated radiation regimens.ConclusionsLGG acts as a ‘time-release capsule’ releasing radioprotective LTA. LTA then primes the epithelial stem cell niche to protect epithelial stem cells by triggering a multicellular, adaptive immune signalling cascade involving macrophages and PGE2 secreting MSCs.Trial registration numberNCT01790035; Pre-results.

scholarly journals Hairless is a nuclear receptor corepressor essential for skin function

2009 ◽  
Vol 7 (1) ◽  
pp. nrs.07010 ◽  
Author(s):  
Catherine C. Thompson
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Nuclear Receptors ◽  
Chromatin Remodeling ◽  
Transcriptional Repression ◽  
Critical Role ◽  
Epithelial Stem Cells ◽  
Skin Function

The activity of nuclear receptors is modulated by numerous coregulatory factors. Corepressors can either mediate the ability of nuclear receptors to repress transcription, or can inhibit transactivation by nuclear receptors. As we learn more about the mechanisms of transcriptional repression, the importance of repression by nuclear receptors in development and disease has become clear. The protein encoded by the mammalian Hairless (Hr) gene was shown to be a corepressor by virtue of its functional similarity to the well-established corepressors N-CoR and SMRT. Mutation of the Hr gene results in congenital hair loss in both mice and men. Investigation of Hairless function both in vitro and in mouse models in vivo has revealed a critical role in maintaining skin and hair by regulating the differentiation of epithelial stem cells, as well as a putative role in regulating gene expression via chromatin remodeling.

scholarly journals Deep Eutectic Solvents for the Extraction of Bioactive Compounds from Natural Sources and Agricultural By-Products

2021 ◽  
Vol 11 (11) ◽  
pp. 4897
Author(s):  
Bárbara Socas-Rodríguez ◽  
M. Vanessa Torres-Cornejo ◽  
Gerardo Álvarez-Rivera ◽  
Jose A. Mendiola
Keyword(s):  
Bioactive Compounds ◽  
Deep Eutectic Solvents ◽  
Extraction Methods ◽  
In Vitro Cytotoxicity ◽  
In Vivo Studies ◽  
Natural Sources ◽  
Natural Deep Eutectic Solvents ◽  
By Products

In this work, a review about the applicability of eutectic solvents, mainly deep eutectic solvents (DES) and natural deep eutectic solvents (NADES), for the extraction of bioactive compounds from natural products has been carried out. These alternative solvents have shown not only to have high extraction yields but also to be environmentally friendly, exhibiting very low or almost no toxicity, compared to conventional organic solvents. The last trends and main extraction methods that have been most widely used in studies using these emerging solvents have been reviewed, as well as the varied natural sources in which they have been used, including agro-food by-products. Besides the toxicity, biodegradability of these solvents is reviewed. Likewise, different reported bioactivity tests have been included, in which extracts obtained with these ecological solvents have been tested from antioxidant activity analysis to in vivo studies with rats, through in vitro cytotoxicity tests.

scholarly journals Bacterial infection drives trained immunity through epigenetic remodeling of epithelial stem cells

2021 ◽  
Author(s):  
Scott Hultgren ◽  
Seongmi Russell ◽  
Hyung Joo Lee ◽  
Benjamin Olson ◽  
Jonathan Livny ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Bacterial Infection ◽  
Bacterial Infections ◽  
Inflammatory Cell ◽  
Host Susceptibility ◽  
Epithelial Stem Cells ◽  
Caspase 1

Abstract Recurrent bacterial infections are a major health burden worldwide, yet the mechanisms dictating host susceptibility to recurrence are poorly understood. Here we demonstrate that an initial bacterial infection of the urinary bladder with uropathogenic E. coli (UPEC) can induce sustained epigenetic changes in the bladder epithelial (urothelial) stem cells that reprogram the differentiated urothelium. We established urothelial stem cell (USC) lines from isogenic mice with different urinary tract infection histories (naïve, chronic or self-resolving). Differentiation of the USC lines in Transwell culture resulted in polarized urothelial cultures that recapitulated distinct remodeling morphologies seen in vivo. In addition, we discovered differences in chromatin accessibility that segregated by disease history, resulting in differences in gene expression upon differentiation of the USC lines in vitro, based on ATAC-seq analysis of the USC lines. Differential basal expression of Caspase-1 led to divergent susceptibilities to inflammatory cell death upon UPEC infection. In mice with a history of chronic infection, enhanced caspase 1-mediated inflammatory cell death was found to be a protective response that enhanced bacterial clearance upon challenge infection. Thus, UPEC infection reshapes the epigenome leading to epithelial-intrinsic remodeling that trains the mucosal immune response to subsequent infection. These findings may have broad implications for the prevention of chronic/recurrent bacterial infections.

Stem cells of the oesophageal epithelium

2002 ◽  
Vol 115 (9) ◽  
pp. 1783-1789
Author(s):  
John P. Seery
Keyword(s):  
Stem Cells ◽  
Cell Biology ◽  
Epithelial Stem Cells ◽  
The Past ◽  
The World

Cancers arising in the oesophageal epithelium are among the most common fatal tumors in the world. Despite this, comparatively little is known about the cell biology and organization of this tissue. Recently, in vitro and in vivo techniques developed over the past 30 years for the study of the epidermis have been applied to the study of the oesophageal epithelium. This approach, combined with data from previous histochemical studies, has lead to the identification and isolation of putative oesophageal epithelial stem cells. Oesophageal epithelial stem cells demonstrate several unusual properties, and their identification may facilitate studies on oesophageal carcinogenesis.

scholarly journals Chemosensitivity of Patient-Derived Cancer Stem Cells Identifies Colorectal Cancer Patients with Potential Benefit from FGFR Inhibitor Therapy

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2010
Author(s):  
Takehito Yamamoto ◽  
Hiroyuki Miyoshi ◽  
Fumihiko Kakizaki ◽  
Hisatsugu Maekawa ◽  
Tadayoshi Yamaura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Genetic Alterations ◽  
Inhibitor Therapy ◽  
Epithelial Stem Cells ◽  
Colorectal Cancer Patients

Some colorectal cancer patients harboring FGFR (fibroblast growth factor receptor) genetic alterations, such as copy number gain, mutation, and/or mRNA overexpression, were selected for enrollment in several recent clinical trials of FGFR inhibitor, because these genetic alterations were preclinically reported to be associated with FGFR inhibitor sensitivity as well as poor prognosis, invasiveness, and/or metastatic potential. However, few enrolled patients were responsive to FGFR inhibitors. Thus, practical strategies are eagerly awaited that can stratify patients for the subset that potentially responds to FGFR inhibitor chemotherapy. In the present study, we evaluated the sensitivity to FGFR inhibitor erdafitinib on 25 patient-derived tumor-initiating cell (TIC) spheroid lines carrying wild-type RAS and RAF genes, both in vitro and in vivo. Then, we assessed possible correlations between the sensitivity and the genetic/genomic data of the spheroid lines tested. Upon their exposure to erdafitinib, seven lines (7/25, 28%) responded significantly. Normal colonic epithelial stem cells were unaffected by the inhibitors. Moreover, the combination of erdafitinib with EGFR inhibitor erlotinib showed stronger growth inhibition than either drug alone, as efficacy was observed in 21 lines (84%) including 14 (56%) that were insensitive to erdafitinib alone. The in vitro erdafitinib response was accurately reflected on mouse xenografts of TIC spheroid lines. However, we found little correlation between their genetic/genomic alterations of TIC spheroids and the sensitivity to the FGFR inhibitor. Accordingly, we propose that direct testing of the patient-derived spheroids in vitro is one of the most reliable personalized methods in FGFR-inhibitor therapy of colorectal cancer patients.

Identification of Epithelial Stem Cells In Vivo and In Vitro Using Keratin 19 and BrdU

2009 ◽  
pp. 383-400 ◽  
Author(s):  
Danielle Larouche ◽  
Amélie Lavoie ◽  
Claudie Paquet ◽  
Carolyne Simard-Bisson ◽  
Lucie Germain
Keyword(s):  
Stem Cells ◽  
Epithelial Stem Cells ◽  
Keratin 19

scholarly journals Bioengineering microfluidic organoids-on-a-chip

2020 ◽  
Author(s):  
Mikhail Nikolaev ◽  
Olga Mitrofanova ◽  
Nicolas Broguiere ◽  
Sara Geraldo ◽  
Yoji Tabata ◽  
...  
Keyword(s):  
Stem Cells ◽  
Model Development ◽  
Cell Types ◽  
Experimental Manipulation ◽  
Epithelial Stem Cells ◽  
Hydrogel Scaffolds ◽  
Microfluidic Perfusion ◽  
Organ Models

Abstract Organoids derived from epithelial stem cells have emerged as powerful platforms to model development and disease in a dish1-3. However, the current mismatch in anatomy, lifespan and size between native organs and their in vitro counterparts severely limits their applicability4. In particular, the closed, cystic architecture of most epithelial stem cell-derived organoids makes experimental manipulation and assay development cumbersome. Here we describe how tissue engineering and cellular self-organization can be combined to guide in vitro organogenesis into openly accessible, functional intestinal tubes termed ‘mini-guts’. Intestinal stem cells (ISCs) rapidly generate simple columnar epithelia when propagated inside basal lamina-like hydrogel scaffolds that feature a tubular and crypt-containing, in vivo-like anatomical structure. Using a microfluidic perfusion system, dead cells shed into the lumen can be continuously removed from the mini-guts. This increases tissue lifespan to months, establishing a homeostatic organoid culture system in which cell proliferation (in crypts) is balanced with cell death (in villus-like domains). The approach developed here can be extended to generate functional tissue/organ models from other epithelial cell types, including primary human stem/progenitor cells from the small intestine, colon or airway, permitting reconstitution of complex organ-level physiology and disease in a personalized manner.

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