scholarly journals The PI3K-Akt pathway inhibits senescence and promotes self-renewal of human skin-derived precursors in vitro

Aging Cell ◽  
2011 ◽  
Vol 10 (4) ◽  
pp. 661-674 ◽  
Author(s):  
Shuang Liu ◽  
Shu Liu ◽  
Xinyue Wang ◽  
Jiaxi Zhou ◽  
Yujing Cao ◽  
...  
Keyword(s):  
Human Skin ◽  
Akt Pathway ◽  
Self Renewal

scholarly journals Enrichment of Female Germline Stem Cells from Mouse Ovaries Using the Differential Adhesion Method

2018 ◽  
Vol 46 (5) ◽  
pp. 2114-2126 ◽  
Author(s):  
Meng Wu ◽  
Jiaqiang Xiong ◽  
Lingwei Ma ◽  
Zhiyong Lu ◽  
Xian Qin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Akt Pathway ◽  
Germline Stem Cells ◽  
Self Renewal ◽  
Differential Adhesion ◽  
Proliferation And Differentiation ◽  
Phosphoinositide 3 Kinase ◽  
Female Germline

Background/Aims: The isolation and establishment of female germline stem cells (FGSCs) is controversial because of questions regarding the reliability and stability of the isolation method using antibody targeting mouse vasa homologue (MVH), and the molecular mechanism of FGSCs self-renewal remains unclear. Thus, there needs to be a simple and reliable method for sorting FGSCs to study them. Methods: We applied the differential adhesion method to enrich FGSCs (DA-FGSCs) from mouse ovaries. Through four rounds of purification and 7-9 subsequent passages, DA-FGSC lines were established. In addition, we assessed the role of the phosphoinositide-3 kinase (PI3K)-AKT pathway in regulating FGSC self-renewal. Results: The obtained DA-FGSCs spontaneously differentiated into oocyte-like cells in vitro and formed functional eggs in vivo that were fertilized and produced healthy offspring. AKT was rapidly phosphorylated when the proliferation rate of FGSCs increased after 10 passages, and the addition of a chemical PI3K inhibitor prevented FGSCs self-renewal. Furthermore, over-expression of AKT-induced proliferation and differentiation of FGSCs, c-Myc, Oct-4 and Gdf-9 levels were increased. Conclusions: The differential adhesion method provides a more feasible approach and is an easier procedure to establish FGSC lines than traditional methods. The AKT pathway plays an important role in regulation of the proliferation and maintenance of FGSCs. These findings could help promote stem cell studies and provide a better understanding of causes of ovarian infertility, thereby providing potential treatments for infertility.

Three-dimensional hydrogel scaffolds facilitate in vitro self-renewal of human skin-derived precursors

2014 ◽  
Vol 10 (7) ◽  
pp. 3177-3187 ◽  
Author(s):  
Xinyue Wang ◽  
Shu Liu ◽  
Qian Zhao ◽  
Na Li ◽  
Huishan Zhang ◽  
...  
Keyword(s):  
Human Skin ◽  
Three Dimensional ◽  
Self Renewal ◽  
Hydrogel Scaffolds

Improved Hematopoietic Differentiation of Primate Embryonic Stem Cells

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2918-2918
Author(s):  
Takenobu Nii ◽  
Tomotoshi Marumoto ◽  
Saori Yamaguchi ◽  
Hirotaka Kawano ◽  
Yoshie Kametani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Regenerative Medicine ◽  
Embryonic Stem ◽  
Hypoxic Condition ◽  
Akt Pathway ◽  
Hematopoietic Differentiation ◽  
Self Renewal ◽  
Cd34 Cells

Abstract Various kinds of functional cells differentiated from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have recently been developed and expected for use in human regenerative medicine. However, the safety and efficacy of ESC/iPSC-based therapies must be carefully evaluated prior to clinical application, by using reliable animal models. The common marmoset (CM, Callithrix jacchus) is known to be a suitable preclinical model for clinical translation studies, and CM ESCs have already been established by us. Hematopoietic stem/progenitor cells (HSCs/HPCs) are one of very useful cells for transplantation therapy to treat various diseases including leukemia. However the shortage of their donors becomes a huge social problem and the expansion of HSCs/HPCs in vitro is known to be very difficult. We have previously demonstrated that CM ESCs showing indefinite self-renewal can be differentiated into hematopoietic lineages by the forced expression of hematopoietic transcription factor (TAL1/SCL). However the efficiency of their hematopoietic differentiation was quite low (less than 5%). Therefore the development of new method to promote hematopoietic differentiation of CM ESCs more efficiently is needed. To promote hematopoietic differentiation of CM ESCs, we focused on self-renewal pathway of CM ESCs and oxygen levels during EB formation. We have reported that self-renewal of CM ESCs is regulated by phosphoinositide 3-kinases (PI3Ks)-protein kinase B (AKT) pathway that is known to regulate cell cycle and cell proliferation as well as cell survival (Nii et al., 2014). On the other hand, the differentiation of mouse ESCs to hematopoietic precursors such as hemangioblasts, bipotential progenitors of endothelial and hematopoietic cells, can be enhanced by hypoxic condition (Ramírez-Bergeron et al., 2004). In addition, expansion of HSCs/HPCs can be increased by hypoxic condition in vitro (Danet et al., 2003). Thus, we hypothesized that the suppression of ESC self-renewal by the inhibition of PI3K-AKT pathway under hypoxic condition would improve hematopoietic differentiation of CM ESCs. To test our hypothesis that the inhibition of self-renewal pathway of CM ESCs could promote their hematopoietic differentiation, we treated CM ESCs with PI3K inhibitor (LY: LY294002) for the first 4 days of EB formation and examined the proportion of CD34+ cells by flow cytometric analysis, and found that the populations of CD34+ cells were significantly increased in the presence of LY. Moreover, the day8-EBs treated with LY gave rise to significantly more hematopoietic colonies than controls in colony forming unit (CFU) assay. These results indicated that hematopoietic differentiation was significantly enhanced by the inhibition of PI3K-AKT pathway in the process of EB formation. To further promote hematopoietic differentiation of CM ESCs, we conducted EB formation assay of CM ESCs and induced their differentiation into HPCs under hypoxic condition. We found that the hypoxic condition (5% O2) significantly increased the proportion of both CD34+ and CD34+/CD117+ cells in day8-EBs especially when PI3K-AKT pathway was inhibited by the LY treatment. These results were also obtained from human ESCs. In the present study, we demonstrated that transient treatment of PI3K inhibitor during EB formation under hypoxia condition promoted hematopoietic differentiation of human and CM ESCs, which might contribute to the development of the valuable experimental system using CM ESCs in order to test new strategies of human regenerative medicine. Disclosures No relevant conflicts of interest to declare.

Desmosomal distribution in the epidermis of a non-contracting human skin equivalent

1992 ◽  
Vol 50 (1) ◽  
pp. 896-897
Author(s):  
L.X. Oakford ◽  
S.D. Dimitrijevich ◽  
R. Gracy
Keyword(s):  
Human Skin ◽  
Basal Layer ◽  
Skin Equivalent ◽  
Tissue Component ◽  
Intact Skin ◽  
Similar Sequence ◽  
Sequence Of Events ◽  
Suprabasal Keratinocytes ◽  
Human Skin Equivalent

In intact skin the epidermal layer is a dynamic tissue component which is maintained by a basal layer of mitotically active cells. The protective upper epidermis, the stratum corneum, is generated by differentiation of the suprabasal keratinocytes which eventually desquamate as anuclear comeocytes. A similar sequence of events is observed in vitro in the non-contracting human skin equivalent (HSE) which was developed in this lab (1). As a part of the definition process for this model of living skin we are examining its ultrastructural features. Since desmosomes are important in maintaining cell-cell interactions in stratified epithelia their distribution in HSE was examined.

Human Skin-Derived Fibroblasts Acquire In Vitro Anti-Tumor Potential after Priming with Paclitaxel

2013 ◽  
Vol 13 (3) ◽  
pp. 523-530 ◽  
Author(s):  
Augusto Pessina ◽  
Valentina Cocce ◽  
Arianna Bonomi ◽  
Loredana Cavicchini ◽  
Francesca Sisto ◽  
...  
Keyword(s):  
Human Skin

scholarly journals Cancer Stem Cell Microenvironment Models with Biomaterial Scaffolds In Vitro

Processes ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 45
Author(s):  
Ghmkin Hassan ◽  
Said M. Afify ◽  
Shiro Kitano ◽  
Akimasa Seno ◽  
Hiroko Ishii ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Biology ◽  
Advanced Technology ◽  
Cancer Microenvironment ◽  
Critical Factors ◽  
Self Renewal ◽  
Cell Microenvironment ◽  
Biological Phenomena ◽  
Biomaterial Scaffolds

Defined by its potential for self-renewal, differentiation and tumorigenicity, cancer stem cells (CSCs) are considered responsible for drug resistance and relapse. To understand the behavior of CSC, the effects of the microenvironment in each tissue are a matter of great concerns for scientists in cancer biology. However, there are many complicated obstacles in the mimicking the microenvironment of CSCs even with current advanced technology. In this context, novel biomaterials have widely been assessed as in vitro platforms for their ability to mimic cancer microenvironment. These efforts should be successful to identify and characterize various CSCs specific in each type of cancer. Therefore, extracellular matrix scaffolds made of biomaterial will modulate the interactions and facilitate the investigation of CSC associated with biological phenomena simplifying the complexity of the microenvironment. In this review, we summarize latest advances in biomaterial scaffolds, which are exploited to mimic CSC microenvironment, and their chemical and biological requirements with discussion. The discussion includes the possible effects on both cells in tumors and microenvironment to propose what the critical factors are in controlling the CSC microenvironment focusing the future investigation. Our insights on their availability in drug screening will also follow the discussion.

The Effect of Practolol, In Vitro Generated Metabolites of Practolol and Chemical Analogues on the Rate of Growth of Human Skin Fibroblasts

1984 ◽  
Vol 12 (2) ◽  
pp. 89-97
Author(s):  
Graham R. Elliott ◽  
H.E. Amos ◽  
James W. Bridges
Keyword(s):  
Human Skin ◽  
Psoriasis Patient ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblasts ◽  
Cell Type ◽  
Normal Human Skin ◽  
Rate Of Growth ◽  
Structural Analogues ◽  
Normal Human

The rate of growth of normal human skin fibroblasts was inhibited in a dose related, reversible, fashion by practolol (N-4-(2-hydroxy)-3 (1-methyl)-aminopropoxyphenylacetamine) (ID50 1.35 ± 0.14 x 10-3M), propranolol (1-(isopropylamino)-3(1-naphthyl-oxy)-2-propranolol) (ID50 0.145 ± 0.02 x 10-3M) and paracetamol (N-(4-hydroxyphenyl) acetamide) (ID50 0.85 ± 0.2 x 10-3M). Skin fibroblasts isolated from a psoriasis patient were more sensitive towards practolol (ID50 0.48 ± 0.14 x 10-3M) and propranolol (ID50 0.032 ± 0.002 x 10-3M), but less sensitive towards paracetamol (ID50 1.3 ± 0.07 x 10-3M). In vitro generated metabolites of practolol, using normal or Arochlor 1254-pretreated hamster liver preparations, and structural analogues of practolol had no effect upon the growth of either cell type.

scholarly journals β-elemene alleviates airway stenosis via the ILK/Akt pathway modulated by MIR143HG sponging miR-1275

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Guoying Zhang ◽  
Cheng Xue ◽  
Yiming Zeng
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Cell Model ◽  
Protective Efficacy ◽  
Rabbit Model ◽  
Akt Pathway ◽  
Loss Of Function ◽  
Airway Stenosis

Abstract Background We have previously found that β-elemene could inhibit the viability of airway granulation fibroblasts and prevent airway hyperplastic stenosis. This study aimed to elucidate the underlying mechanism and protective efficacy of β-elemene in vitro and in vivo. Methods Microarray and bioinformatic analysis were used to identify altered pathways related to cell viability in a β-elemene-treated primary cell model and to construct a β-elemene-altered ceRNA network modulating the target pathway. Loss of function and gain of function approaches were performed to examine the role of the ceRNA axis in β-elemene's regulation of the target pathway and cell viability. Additionally, in a β-elemene-treated rabbit model of airway stenosis, endoscopic and histological examinations were used to evaluate its therapeutic efficacy and further verify its mechanism of action. Results The hyperactive ILK/Akt pathway and dysregulated LncRNA-MIR143HG, which acted as a miR-1275 ceRNA to modulate ILK expression, were suppressed in β-elemene-treated airway granulation fibroblasts; β-elemene suppressed the ILK/Akt pathway via the MIR143HG/miR-1275/ILK axis. Additionally, the cell cycle and apoptotic phenotypes of granulation fibroblasts were altered, consistent with ILK/Akt pathway activity. In vivo application of β-elemene attenuated airway granulation hyperplasia and alleviated scar stricture, and histological detections suggested that β-elemene's effects on the MIR143HG/miR-1275/ILK axis and ILK/Akt pathway were in line with in vitro findings. Conclusions MIR143HG and ILK may act as ceRNA to sponge miR-1275. The MIR143HG/miR-1275/ILK axis mediates β-elemene-induced cell cycle arrest and apoptosis of airway granulation fibroblasts by modulating the ILK/Akt pathway, thereby inhibiting airway granulation proliferation and ultimately alleviating airway stenosis.

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