scholarly journals 626 Early-stage bilayer tissue-engineered skin substitute formed by adult skin progenitor cells produces an improved skin structure in vivo

2021 ◽  
Vol 141 (5) ◽  
pp. S109
Author(s):  
Q. Zhang ◽  
X. Wu
Keyword(s):  
Progenitor Cells ◽  
Early Stage ◽  
Skin Substitute ◽  
Skin Structure ◽  
Adult Skin

scholarly journals Early-stage bilayer tissue-engineered skin substitute formed by adult skin progenitor cells produces an improved skin structure in vivo

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Qun Zhang ◽  
Jie Wen ◽  
Chang Liu ◽  
Chuan Ma ◽  
Fuxiang Bai ◽  
...  
Keyword(s):  
Wound Healing ◽  
Progenitor Cells ◽  
Late Stage ◽  
Early Stage ◽  
Hair Follicles ◽  
Immunofluorescent Staining ◽  
Type I ◽  
Apoptotic Pathway ◽  
Skin Structure

Abstract Background In recent years, significant progress has been made in developing highly complex tissue-engineered skin substitutes (TESSs) for wound healing. However, the lack of skin appendages, such as hair follicles and sweat glands, and the time required, are two major limitations that hinder its broad application in the clinic. Therefore, it is necessary to develop a competent TESS in a short time to meet the needs for clinical applications. Methods Adult scalp dermal progenitor cells and epidermal stem cells together with type I collagen as a scaffold material were used to reconstitute bilayer TESSs in vitro. TESSs at 4 different culture times (5, 9, 14, and 21 days) were collected and then grafted onto full-thickness wounds created in the dorsal skin of athymic nude/nude mice. The skin specimens formed from grafted TESSs were collected 4 and 8 weeks later and then evaluated for their structure, cell organization, differentiation status, vascularization, and formation of appendages by histological analysis, immunohistochemistry, and immunofluorescent staining. Results Early-stage bilayer TESSs after transplantation had a better efficiency of grafting. A normal structure of stratified epidermis containing multiple differentiated layers of keratinocytes was formed in all grafts from both early-stage and late-stage TESSs, but higher levels of the proliferation marker Ki-67 and the epidermal progenitor marker p63 were found in the epidermis formed from early-stage TESSs. Interestingly, the transplantation of early-stage TESSs produced a thicker dermis that contained more vimentin- and CD31-positive cells, and importantly, hair follicle formation was only observed in the skin grafted from early-stage TESSs. Finally, early-stage TESSs expressed high levels of p63 but had low expression levels of genes involved in the activation of the apoptotic pathway compared to the late-stage TESSs in vitro. Conclusions Early-stage bilayer TESSs reconstituted from skin progenitor cells contained more competent cells with less activation of the apoptotic pathway and produced a better skin structure, including hair follicles associated with sebaceous glands, after transplantation, which should potentially provide better wound healing when applied in the clinic in the future.

scholarly journals A cancer stem cell origin for human endometrial carcinoma?

Reproduction ◽  
2010 ◽  
Vol 140 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Sonya A Hubbard ◽  
Caroline E Gargett
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Early Stage ◽  
Side Population ◽  
Tumour Cells ◽  
Treatment Modalities ◽  
Western World ◽  
Differentiated Cells ◽  
New Treatment

Endometrial cancer (EC) is the most common gynaecological malignancy affecting women in the western world. Cancer stem cells (CSCs) are defined as a subset of tumour cells with the capacity to self-renew and give rise to the differentiated cells that comprise the bulk of the tumour. Given that a rare population of epithelial stem/progenitor cells has been identified in human endometrium, it is possible that these cells or their progeny may be the source of the putative CSCs that may initiate and maintain EC. Studies have shown that some cells within EC have the capacity to initiate clones that undergo self-renewing cell division and form tumoursin vivothat can be serially passaged, demonstrating self-renewal, proliferation and differentiation abilities of the potential EC stem cells (ECSCs). These potential ECSCs may be located within the tumour cell population expressing CD133 and/or within the side population. With the discovery of markers for ECSCs, it is hoped that ECSCs can be isolated and characterised, and that their role in the development of human EC will be further investigated. This knowledge opens the way for the development of new treatment modalities that target the CSCs, but spares normal endometrial stem/progenitor cells and other cells. Such treatments will be particularly useful for early-stage and pre-menopausal EC candidates where the uterus may be conserved, and for late-stage cases where hysterectomy is not curative and current treatments target the bulk tumour cells rather than CSCs.

Adenosine Diphosphate (ADP)-Induced ⍺-Granules Release from Platelets of Native Whole Blood Is Reduced by Ticlopidine but Not by Aspirin or Dipyridamole

1986 ◽  
Vol 56 (02) ◽  
pp. 147-150 ◽  
Author(s):  
V Pengo ◽  
M Boschello ◽  
A Marzari ◽  
M Baca ◽  
L Schivazappa ◽  
...  
Keyword(s):  
Whole Blood ◽  
Light Transmission ◽  
Ex Vivo ◽  
Early Stage ◽  
Shape Change ◽  
Adenosine Diphosphate ◽  
Dose Dependent ◽  
Plateletderived Growth Factor ◽  
Platelet Shape

SummaryA brief contact between native whole blood and ADP promotes a dose-dependent release of platelet a-granules without a fall in the platelet number. We assessed the “ex vivo” effect of three widely used antiplatelet drugs, aspirin dipyridamole and ticlopidine, on this system. Aspirin (a single 800 mg dose) and dipyridamole (300 mg/die for four days) had no effect, while ticlopidine (500 mg/die for four days) significantly reduced the a-granules release for an ADP stimulation of 0.4 (p <0.02), 1.2 (p <0.01) and 2 pM (p <0.01). No drug, however, completeley inhibits this early stage of platelet activation. The platelet release of α-granules may be related to platelet shape change of the light transmission aggregometer and may be important “in vivo” by enhancing platelet adhesiveness and by liberating the plateletderived growth factor.

Bone Marrow Niches for Skeletal Progenitor Cells and their Inhabitants in Health and Disease

2019 ◽  
Vol 14 (4) ◽  
pp. 305-319 ◽  
Author(s):  
Marietta Herrmann ◽  
Franz Jakob
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Adult Stem Cells ◽  
Current Knowledge ◽  
Cell Populations ◽  
Surface Markers ◽  
Bone Marrow Niches

The bone marrow hosts skeletal progenitor cells which have most widely been referred to as Mesenchymal Stem or Stromal Cells (MSCs), a heterogeneous population of adult stem cells possessing the potential for self-renewal and multilineage differentiation. A consensus agreement on minimal criteria has been suggested to define MSCs in vitro, including adhesion to plastic, expression of typical surface markers and the ability to differentiate towards the adipogenic, osteogenic and chondrogenic lineages but they are critically discussed since the differentiation capability of cells could not always be confirmed by stringent assays in vivo. However, these in vitro characteristics have led to the notion that progenitor cell populations, similar to MSCs in bone marrow, reside in various tissues. MSCs are in the focus of numerous (pre)clinical studies on tissue regeneration and repair.Recent advances in terms of genetic animal models enabled a couple of studies targeting skeletal progenitor cells in vivo. Accordingly, different skeletal progenitor cell populations could be identified by the expression of surface markers including nestin and leptin receptor. While there are still issues with the identity of, and the overlap between different cell populations, these studies suggested that specific microenvironments, referred to as niches, host and maintain skeletal progenitor cells in the bone marrow. Dynamic mutual interactions through biological and physical cues between niche constituting cells and niche inhabitants control dormancy, symmetric and asymmetric cell division and lineage commitment. Niche constituting cells, inhabitant cells and their extracellular matrix are subject to influences of aging and disease e.g. via cellular modulators. Protective niches can be hijacked and abused by metastasizing tumor cells, and may even be adapted via mutual education. Here, we summarize the current knowledge on bone marrow skeletal progenitor cell niches in physiology and pathophysiology. We discuss the plasticity and dynamics of bone marrow niches as well as future perspectives of targeting niches for therapeutic strategies.

scholarly journals Myelin basic protein enhances axonal regeneration from neural progenitor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhengjian Yan ◽  
Lei Chu ◽  
Xiaojiong Jia ◽  
Lu Lin ◽  
Si Cheng
Keyword(s):  
Myelin Basic Protein ◽  
Neurite Outgrowth ◽  
Progenitor Cells ◽  
Axonal Regeneration ◽  
Neural Progenitor Cells ◽  
Basic Protein ◽  
Neural Progenitor ◽  
Dependent Manner ◽  
Cord Injury

Abstract Introduction Stem cell therapy using neural progenitor cells (NPCs) shows promise in mitigating the debilitating effects of spinal cord injury (SCI). Notably, myelin stimulates axonal regeneration from mammalian NPCs. This led us to hypothesize that myelin-associated proteins may contribute to axonal regeneration from NPCs. Methods We conducted an R-based bioinformatics analysis to identify key gene(s) that may participate in myelin-associated axonal regeneration from murine NPCs, which identified the serine protease myelin basic protein (Mbp). We employed E12 murine NPCs, E14 rat NPCs, and human iPSC-derived Day 1 NPCs (D1 hNPCs) with or without CRISPR/Cas9-mediated Mbp knockout in combination with rescue L1-70 overexpression, constitutively-active VP16-PPARγ2, or the PPARγ agonist ciglitazone. A murine dorsal column crush model of SCI utilizing porous collagen-based scaffolding (PCS)-seeded murine NPCs with or without stable Mbp overexpression was used to assess locomotive recovery and axonal regeneration in vivo. Results Myelin promotes axonal outgrowth from NPCs in an Mbp-dependent manner and that Mbp’s stimulatory effects on NPC neurite outgrowth are mediated by Mbp’s production of L1-70. Furthermore, we determined that Mbp/L1-70’s stimulatory effects on NPC neurite outgrowth are mediated by PPARγ-based repression of neuron differentiation-associated gene expression and PPARγ-based Erk1/2 activation. In vivo, PCS-seeded murine NPCs stably overexpressing Mbp significantly enhanced locomotive recovery and axonal regeneration in post-SCI mice. Conclusions We discovered that Mbp supports axonal regeneration from mammalian NPCs through the novel Mbp/L1cam/Pparγ signaling pathway. This study suggests that bioengineered, NPC-based interventions can promote axonal regeneration and functional recovery post-SCI.

scholarly journals Perivascular vital cells in the ablation center after multibipolar radiofrequency ablation in an in vivo porcine model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
F. G. M. Poch ◽  
C. A. Neizert ◽  
B. Geyer ◽  
O. Gemeinhardt ◽  
S. M. Niehues ◽  
...  
Keyword(s):  
Radiofrequency Ablation ◽  
Early Stage ◽  
Pringle Maneuver ◽  
Vessel Diameter ◽  
Inflow Occlusion ◽  
White Zone ◽  
Cell Vitality ◽  
Internally Cooled ◽  
Hepatic Vessels

AbstractMultibipolar radiofrequency ablation (RFA) is an advanced ablation technique for early stage hepatocellular carcinoma and liver metastases. Vessel cooling in multibipolar RFA has not been systematically investigated. The objective of this study was to evaluate the presence of perivascular vital cells within the ablation zone after multibipolar RFA. Multibipolar RFA were performed in domestic pigs in vivo. Three internally cooled bipolar RFA applicators were used simultaneously. Three experimental settings were planned: (1) inter-applicator-distance: 15 mm; (2) inter-applicator-distance: 20 mm; (3) inter-applicator-distance: 20 mm with hepatic inflow occlusion (Pringle maneuver). A vitality staining was used to analyze liver cell vitality around all vessels in the ablation center with a diameter > 0.5 mm histologically. 771 vessels were identified. No vital tissue was seen around 423 out of 429 vessels (98.6%) situated within the central white zone. Vital cells could be observed around major hepatic vessels situated adjacent to the ablation center. Vessel diameter (> 3.0 mm; p < 0.05) and low vessel-to-ablation-center distance (< 0.2 mm; p < 0.05) were identified as risk factors for incomplete ablation adjacent to hepatic vessels. The vast majority of vessels, which were localized in the clinically relevant white zone, showed no vital perivascular cells, regardless of vessel diameter and vessel type. However, there was a risk of incomplete ablation around major hepatic vessels situated directly within the ablation center. A Pringle maneuver could avoid incomplete ablations.

scholarly journals Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro

2021 ◽  
Vol 22 (3) ◽  
pp. 1390
Author(s):  
Julia Mester-Tonczar ◽  
Patrick Einzinger ◽  
Johannes Winkler ◽  
Nina Kastner ◽  
Andreas Spannbauer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Progenitor Cells ◽  
Regulatory Networks ◽  
Circular Rnas ◽  
Cardiac Progenitor Cells ◽  
Tissue Samples ◽  
Healthy Myocardium ◽  
Acute Mi

Circular RNAs (circRNAs) are crucial in gene regulatory networks and disease development, yet circRNA expression in myocardial infarction (MI) is poorly understood. Here, we harvested myocardium samples from domestic pigs 3 days after closed-chest reperfused MI or sham surgery. Cardiac circRNAs were identified by RNA-sequencing of rRNA-depleted RNA from infarcted and healthy myocardium tissue samples. Bioinformatics analysis was performed using the CIRIfull and KNIFE algorithms, and circRNAs identified with both algorithms were subjected to differential expression (DE) analysis and validation by qPCR. Circ-RCAN2 and circ-C12orf29 expressions were significantly downregulated in infarcted tissue compared to healthy pig heart. Sanger sequencing was performed to identify the backsplice junctions of circular transcripts. Finally, we compared the expressions of circ-C12orf29 and circ-RCAN2 between porcine cardiac progenitor cells (pCPCs) that were incubated in a hypoxia chamber for different time periods versus normoxic pCPCs. Circ-C12orf29 did not show significant DE in vitro, whereas circ-RCAN2 exhibited significant ischemia-time-dependent upregulation in hypoxic pCPCs. Overall, our results revealed novel cardiac circRNAs with DE patterns in pCPCs, and in infarcted and healthy myocardium. Circ-RCAN2 exhibited differential regulation by myocardial infarction in vivo and by hypoxia in vitro. These results will improve our understanding of circRNA regulation during acute MI.

scholarly journals Probing the Intracellular Bio-Nano Interface in Different Cell Lines with Gold Nanostars

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1183
Author(s):  
Cecilia Spedalieri ◽  
Gergo Péter Szekeres ◽  
Stephan Werner ◽  
Peter Guttmann ◽  
Janina Kneipp
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Early Stage ◽  
Protein Corona ◽  
Fibroblast Cell ◽  
Ultrastructural Level ◽  
Epithelial Cell Line ◽  
Animal Cells ◽  
Gold Nanostars

Gold nanostars are a versatile plasmonic nanomaterial with many applications in bioanalysis. Their interactions with animal cells of three different cell lines are studied here at the molecular and ultrastructural level at an early stage of endolysosomal processing. Using the gold nanostars themselves as substrate for surface-enhanced Raman scattering, their protein corona and the molecules in the endolysosomal environment were characterized. Localization, morphology, and size of the nanostar aggregates in the endolysosomal compartment of the cells were probed by cryo soft-X-ray nanotomography. The processing of the nanostars by macrophages of cell line J774 differed greatly from that in the fibroblast cell line 3T3 and in the epithelial cell line HCT-116, and the structure and composition of the biomolecular corona was found to resemble that of spherical gold nanoparticles in the same cells. Data obtained with gold nanostars of varied morphology indicate that the biomolecular interactions at the surface in vivo are influenced by the spike length, with increased interaction with hydrophobic groups of proteins and lipids for longer spike lengths, and independent of the cell line. The results will support optimized nanostar synthesis and delivery for sensing, imaging, and theranostics.

scholarly journals Synthesis and Characterization of Exopolysaccharide Encapsulated PCL/Gelatin Skin Substitute for Full-Thickness Wound Regeneration

Polymers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 854
Author(s):  
Ahmad Hivechi ◽  
Peiman Brouki Milan ◽  
Khashayar Modabberi ◽  
Moein Amoupour ◽  
Kaveh Ebrahimzadeh ◽  
...  
Keyword(s):  
Cell Activity ◽  
Average Diameter ◽  
Skin Substitute ◽  
Full Thickness ◽  
Skin Integrity ◽  
Hematoxylin And Eosin ◽  
First Time ◽  
Full Thickness Wound

Loss of skin integrity can lead to serious problems and even death. In this study, for the first time, the effect of exopolysaccharide (EPS) produced by cold-adapted yeast R. mucilaginosa sp. GUMS16 on a full-thickness wound in rats was evaluated. The GUMS16 strain’s EPS was precipitated by adding cold ethanol and then lyophilized. Afterward, the EPS with polycaprolactone (PCL) and gelatin was fabricated into nanofibers with two single-needle and double-needle procedures. The rats’ full-thickness wounds were treated with nanofibers and Hematoxylin and eosin (H&E) and Masson’s Trichrome staining was done for studying the wound healing in rats. Obtained results from SEM, DLS, FTIR, and TGA showed that EPS has a carbohydrate chemical structure with an average diameter of 40 nm. Cell viability assessments showed that the 2% EPS loaded sample exhibits the highest cell activity. Moreover, in vivo implantation of nanofiber webs on the full-thickness wound on rat models displayed a faster healing rate when EPS was loaded into a nanofiber. These results suggest that the produced EPS can be used for skin tissue engineering applications.

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