scholarly journals Glioblastoma embryonic-like stem cells exhibit immune-evasive phenotype

2021 ◽  
Author(s):  
Borja Sese ◽  
Sandra Iniguez ◽  
Miquel Arash Ensenat ◽  
Pere Llinas ◽  
Guillem Ramis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Population ◽  
Immune Evasion ◽  
Cell Mass ◽  
Induced Pluripotent Stem Cell ◽  
Stem Cell Population ◽  
Glioma Stem Cells ◽  
Pluripotency Markers

Glioma stem cells (GSCs) are a subset of cells with self-renewal and tumor-initiating capacities that are thought to participate in drug resistance and immune evasion mechanisms in glioblastoma (GBM). Given GBM heterogeneity, we hypothesized that GSCs might also display cellular hierarchies associated with different degrees of stemness. We evaluated a single-cell RNA-seq glioblastoma dataset (n = 28) and identified a stem cell population co-expressing high levels of embryonic pluripotency markers, named core glioma stem cells (c-GSCs). This embryonic-like population represents 4.22% of the tumor cell mass, and pathway analysis revealed an upregulation of stemness and downregulation of immune-associated pathways. Using induced pluripotent stem cell technology, we generated an in vitro model of c-GSCs by reprogramming glioblastoma patient-derived cells into induced c-GSCs (ic-GSCs). Immunostaining of ic-GSCs showed high expression of embryonic pluripotency markers and downregulation of antigen presentation HLA proteins, mimicking its tumoral counterpart. Transcriptomic analysis revealed a strong agreement of enriched biological pathways between tumor c-GSCs and in vitro ic-GSCs (k = 0.71). Integration of ic-GSC DNA methylation and gene expression with chromatin state analysis of epigenomic maps (n = 833) indicated that polycomb repressive marks downregulate HLA genes in stem-like phenotype. Together, we identified c-GSCs as a GBM cell population with embryonic signatures and poor immunogenicity. Genome-scale transcriptomic and epigenomic profiling provide a valuable resource for studying immune evasion mechanisms governing c-GSCs and identifying potential therapeutic targets for GBM immunotherapy.

scholarly journals Comparison of the Biological and Functional Characteristics of Mesenchymal Stem Cells From Intrahepatic and Identical Bone Marrow

2020 ◽  
Author(s):  
Hongyu Zhang ◽  
Jiejuan Lai ◽  
Shifang Jiang ◽  
Ling Shuai ◽  
Yujun Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Conditioned Medium ◽  
Cell Population ◽  
Neutralizing Antibodies ◽  
Stem Cell Population ◽  
Functional Characteristics ◽  
Fibrotic Liver

Abstract Background: We previously isolated a novel mesenchymal stem cell (MSC)-like neuroglial antigen 2-expressing stem cell population (MLpvNG2) from an uninjured liver by using a “Porcoll-Plate-Wait” method and determined that MLpvNG2 possesses hepatic stem/progenitor cell characteristics.Methods: In this study, we compared the biological and functional characteristics of the intrahepatic (MSC)-like MLpvNG2 with identical bone marrow-derived MSCs (niBM-MSCs), which are a well-accepted stem cell population in the field. We performed an in vitro study using conditioned medium and in vivo study using our well-set diethylnitrosamine (DEN)-induced liver fibrotic/cirrhotic murine model as well. Results: We found that in a fibrotic liver environment, MLpvNG2 survived better than niBM-MSCs obtained through different mechanisms of action. MLpvNG2 mainly differentiates into albumin (ALB(+)) hepatocytes, while niBM-MSCs mainly differentiate into CK/KRT19(+) cholangiocytes. Of note, we identified for the first time that C/EBPα/β is expressed on the cell surface of donor and host hepatic cells. As such, we used anti-C/EBPs neutralizing antibodies to determine the functional characteristics both in vitro (conditioned medium) and in the DEN-induced animal model.Conclusions: Based on our findings, it can be concluded that native-source (liver) stem cells (MLpvNG2) are more efficient than nonnative-sourced stem cells (niBM-MSCs) in the treatment of native (liver)-sourced diseases such as end-stage liver disease.

Stem cells in mammary health and milk production

2021 ◽  
Vol 16 ◽  
Author(s):  
Ratan K Choudhary ◽  
Fenq-Qi Zhao
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Population ◽  
Adult Stem Cells ◽  
Stem Cell Population ◽  
Mammary Stem ◽  
In Vitro Expansion

: Adult stem cells like mammary and mesenchymal stem cells have received significant attention because these stem cells (SCs) possess therapeutic potential in treating many animal diseases. These cells can be administered in an autologous or allogenic fashion, either freshly isolated from the donor tissue or previously cultured and expanded in vitro. Expansion of adult stem cells is a prerequisite before therapeutic application because sufficient numbers are required in dosage calculation. Stem cells directly and indirectly (by secreting various growth factors and angiogenic factors called secretome) act to repair and regenerate injured tissues. Recent studies on mammary stem cells showed in vivo and in vitro expansion ability by removing the blockage of asymmetrical cell division. Compounds like purine analogs (xanthosine, xanthine, and inosine) or hormones (progesterone and bST) help increase stem cell population by promoting cell division. Such methodology of enhancing stem cells number, either in vivo or in vitro, may help in preclinical studies for translational research like treating diseases like mastitis. The application of mesenchymal stem cells has also been shown to benefit mammary gland health due to the ‘homing’ property of stem cells. In addition to that, the multiple positive effects of stem cell secretome are on mammary tissue healing and killing bacteria is novel in the production of quality milk. This systematic review discusses some of the studies on stem cells that have been useful in increasing the stem cell population and increasing mammary stem/progenitor cells. Finally, we provide insights into how enhancing mammary stem cell population could potentially increase terminally differentiated cells, ultimately leading to more milk production.

scholarly journals 3D Differentiation Of Mammosphere Derived Macaca fascicularis’s Mammary Stem Cells

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Silmi Mariya
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mammary Gland ◽  
Cell Population ◽  
Mammary Stem Cell ◽  
Stem Cell Population ◽  
Stem Cell Markers ◽  
Mammary Stem Cells ◽  
Surgical Biopsy ◽  
Mammary Stem

The mammary gland contains adult stem cells that are capable of self-renewal.  This population plays an important role in the development of mammary gland and breast cancer pathogenesis. The studies of mammary stem cells are limited due to the difficulty to acquire and expand adult stem cell population in an undifferentiated state. In this study, we developed mammosphere cultures of nulliparous cynomolgus monkeys (Macaca fascicularis; Mf) as a culture system to enrich mammary stem cells. This species has similarity of mammary gland structure as humans including anatomy, developmental stages, and lobule profile of mammary gland. The use of stem cells from primate animals is essential to bridge the knowledge gaps resulting from stem cell research using rodents for clinical trials in human. Small samples of mammary tissues were collected by surgical biopsy; cells were cultured as monolayer and cryopreserved. Cryopreserved cells were cultured into mammospheres, and the expression of markers for mammary stem cells was evaluated using qPCR. Cells were further differentiated with 3D approaches to evaluate morphology and organoid budding. The study showed that mammosphere culture resulted in an increase in the expression of mammary stem cell markers with each passage. The 3D differentiation in matrigel allowed for organoid formation. Mammary gland stem cells have been successfully differentiated which characterized by CSN2 marker expression and differentiation regulators marker STAT5 and GATA3. The results indicate that mammospheres can be successfully developed derived from breast tissue of nulliparous Mf collected via surgical biopsy. As the mammosphere allows for enrichment of mammary stem cell population, the findings also suggest that a 3-dimensional system is efficient as in-vitro model to study mammary stem cells and a useful system to study mammary differentiation in regards to cancer prevention.

scholarly journals PIWIL1 Drives Chemoresistance in Multiple Myeloma by Modulating Mitophagy and the Myeloma Stem Cell Population

2022 ◽  
Vol 11 ◽  
Author(s):  
Yajun Wang ◽  
Lan Yao ◽  
Yao Teng ◽  
Hua Yin ◽  
Qiuling Wu
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Stem Cell ◽  
Cell Population ◽  
Side Population ◽  
Chemotherapeutic Agents ◽  
Stem Cell Population ◽  
Exact Function

As an important member of the Argonaute protein family, PIWI-like protein 1 (PIWIL1) plays a key role in tumor cell viability. However, the exact function of PIWIL1 in multiple myeloma (MM) and the underlying mechanism remain unclear. Here, we revealed that PIWIL1 was highly expressed in myeloma cell lines and newly diagnosed MM patients, and that its expression was notably higher in refractory/relapsed MM patients. PIWIL1 promoted the proliferation of MM cells and conferred resistance to chemotherapeutic agents both in vitro and in vivo. More importantly, PIWIL1 enhanced the formation of autophagosomes, especially mitophagosomes, by disrupting mitochondrial calcium signaling and modulating mitophagy-related canonical PINK1/Parkin pathway protein components. Mitophagy/autophagy inhibitors overcome PIWIL1-induced chemoresistance. In addition, PIWIL1 overexpression increased the proportion of side population (SP) cells and upregulated the expression of the stem cell-associated genes Nanog, OCT4, and SOX2, while its inhibition resulted in opposite effects. Taken together, our findings demonstrated that PIWIL1 induced drug resistance by activating mitophagy and regulating the MM stem cell population. PIWIL1 depletion significantly overcame drug resistance and could be used as a novel therapeutic target for reversing resistance in MM patients.

Characterization and in vitro hematopoietic capacity of a very small embryonic like stem cell population isolated from human cord blood

Cytotherapy ◽  
2017 ◽  
Vol 19 (5) ◽  
pp. S77-S78
Author(s):  
E. Gounari ◽  
A. Daniilidis ◽  
I. Koliakou ◽  
N. Tsagias ◽  
K. Kouzi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Cell Population ◽  
Stem Cell Population ◽  
Human Cord Blood

396 Oct-4 EXPRESSION IN CAT INNER CELL MASS-DERIVED CELLS CULTURED IN MEDIUM WITH DIFFERENT PROTEIN SOURCES

2010 ◽  
Vol 22 (1) ◽  
pp. 354
Author(s):  
T. S. Rascado ◽  
J. F. Lima-Neto ◽  
S. E. R. S. Lorena ◽  
B. W. Minto ◽  
F. C. Landim-Alvarenga
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Inner Cell Mass ◽  
Culture Media ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Domestic Cat ◽  
Santa Cruz

The domestic cat can be used as a biological model for humans because of similarities in some disease and genetically transmitted conditions. Embryonic stem cells might complete nuclear reprogramming more efficiently than somatic cells and, therefore, are potentially useful for increasing interspecific cloning success. The objective of this study was to establish an effective culture system for inner cell mass (ICM)-derived cells in the domestic cat, testing the ability of the ICM to attach to the culture dish and to form embryonic stem cell colonies in the presence of fetal calf serum (FCS) and Knockout serum (KS). Moreover, knowing that the transcription factor Oct-4 is important for the maintenance of pluripotency in human and murine embryonic stem cells, the expression of this factor was evaluated in in vitro-produced blastocyst and in the attached ICM. Domestic cat oocytes were matured, fertilized, and cultured in vitro until the blastocyst stage. The ICM was mechanically isolated (n = 60) using a scalpel blade and transferred to a monolayer of chemically inactivated cat fibroblasts with 10 μg mL-1 mitomicin C. The base culture media (BM) was DMEM/F12 supplemented with nonessential amino acids, glutamine, leukemia inhibitory factor, fibroblast growth factor-2, 2-mercaptoethanol, and antibiotics. Three groups were tested: G1 = BM with 20% FCS (20); G2 = BM with 20% KS (20); G3 = BM with 15% FSC and 5% KS (20). Culture was performed in a 5% CO2 in air incubator at 38.5°C. No statistical difference was observed among groups in relation to ICM attachment (chi-square, P > 0.05). Ninety percent of the ICM presented good adhesion after 3 days of culture and started to grow in all media tested. However, until now, no good colonies were formed. Fifteen blastocysts and 10 attached ICM were fixed in 3% paraformaldehyde and permeabilized in 0.2% triton X-100 in PBS. Subsequently, to block nonspecific binding of the primary antibody, the preadsorption for 2 h at room temperature with OCT4 blocking peptide (sc-8628P, Santa Cruz Biotechnology, Santa Cruz, CA, USA) was used. Samples were incubated with Oct4 antibody (N-19 : sc 8628, Santa Cruz Biotechnology) and with the appropriate secondary antibody (A21431, Invitrogen) and examined by fluorescence microscopy. Oct4 protein was detected both in the ICM and trophoderm cells, and it was distributed in cytoplasm and nuclei. These embryos were also stained with Hoechst 33342. Although further standardization of the culture media is needed, it seems that the KS can be replaced by FCS in cat embryonic stem cell culture. Furthermore, the immunostain of the trophoderm with Oct-4 indicates a difference in the expression of this factor when compared with its expression on human and murine blastocysts. This could be related to in vitro production, or Oct 4 is not a good pluripotency marker for cat embryos and cat embryonic stem cell, consequently. This fact has been noted in goat, bovine, and porcine embryos. Acknowledgment is given to FAPESP.

scholarly journals 5-Azacytidine-Induced Cardiomyocyte Differentiation of Very Small Embryonic-Like Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
XiaoLin Sun ◽  
HongXiao Li ◽  
Ye Zhu ◽  
Pei Xu ◽  
QiSheng Zuo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ethical Issues ◽  
Troponin T ◽  
Embryonic Stem ◽  
Stem Cell Population ◽  
Pacemaker Activity ◽  
Stem Cell Markers ◽  
Seed Cells

The use of stem cells in generating cell-based pacemaker therapies for bradyarrhythmia is currently being considered. Due to the propensity of stem cells to form tumors, as well as ethical issues surrounding their use, the seed cells used in cardiac biological pacemakers have limitations. Very small embryonic-like stem cells (VSELs) are a unique and rare adult stem cell population, which have the same structural, genetic, biochemical, and functional characteristics as embryonic stem cells without the ethical controversy. In this study, we investigated the ability of rat bone marrow- (BM-) derived VSELs to differentiate in vitro into cardiomyocytes by 5-Azacytidine (5-AzaC) treatment. The morphology of VSELs treated with 10 μM 5-AzaC increased in volume and gradually changed to cardiomyocyte-like morphology without massive cell death. Additionally, mRNA expression of the cardiomyocyte markers cardiac troponin-T (cTnT) and α-sarcomeric actin (α-actin) was significantly upregulated after 5-AzaC treatment. Conversely, stem cell markers such as Nanog, Oct-4, and Sox2 were continuously downregulated posttreatment. On day 14 post-5-AzaC treatment, the positive expression rates of cTnT and α-actin were 18.41±1.51% and 19.43±0.51%, respectively. Taken together, our results showed that rat BM-VSELs have the ability to differentiate into cardiomyocytes in vitro. These findings suggest that VSELs would be useful as seed cells in exploring the mechanism of biological pacemaker activity.

scholarly journals Modelling stem cell ageing: a multi-compartment continuum approach

2020 ◽  
Vol 7 (3) ◽  
pp. 191848
Author(s):  
Yanli Wang ◽  
Wing-Cheong Lo ◽  
Ching-Shan Chou
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Population ◽  
Damage Accumulation ◽  
Cell Cycle Progression ◽  
Cell Damage ◽  
Life Stage ◽  
Early Life Stage ◽  
Stem Cell Population ◽  
Equal Distribution

Stem cells are important to generate all specialized tissues at an early life stage, and in some systems, they also have repair functions to replenish the adult tissues. Repeated cell divisions lead to the accumulation of molecular damage in stem cells, which are commonly recognized as drivers of ageing. In this paper, a novel model is proposed to integrate stem cell proliferation and differentiation with damage accumulation in the stem cell ageing process. A system of two structured PDEs is used to model the population densities of stem cells (including all multiple progenitors) and terminally differentiated (TD) cells. In this system, cell cycle progression and damage accumulation are modelled by continuous dynamics, and damage segregation between daughter cells is considered at each division. Analysis and numerical simulations are conducted to study the steady-state populations and stem cell damage distributions under different damage segregation strategies. Our simulations suggest that equal distribution of the damaging substance between stem cells in a symmetric renewal and less damage retention in stem cells in the asymmetric division are favourable strategies, which reduce the death rate of the stem cells and increase the TD cell populations. Moreover, asymmetric damage segregation in stem cells leads to less concentrated damage distribution in the stem cell population, which may be more robust to the stochastic changes in the damage. The feedback regulation from stem cells can reduce oscillations and population overshoot in the process, and improve the fitness of stem cells by increasing the percentage of cells with less damage in the stem cell population.

scholarly journals The Junctional Epithelium Is Maintained by a Stem Cell Population

2020 ◽  
pp. 002203452096012
Author(s):  
X. Yuan ◽  
J. Chen ◽  
J.A. Grauer ◽  
Q. Xu ◽  
L.A. Van Brunt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Bone Resorption ◽  
Cell Population ◽  
Barrier Function ◽  
The Body ◽  
Stem Cell Population ◽  
Oral Epithelium ◽  
Junctional Epithelium ◽  
Slow Cycling

The most fundamental function of an epithelial tissue is to act as a barrier, regulating interactions between the external environment and the body. This barrier function typically requires a contiguous cell layer but since teeth penetrate the oral epithelium, a modified barrier has evolved, called the junctional epithelium (JE). In health, the JE attaches to the tooth, sealing the inside of the body against oral micro-organisms. Breakdown of the JE barrier results in periodontal ligament (PDL) disintegration, alveolar bone resorption, and ultimately tooth loss. Using lineage tracing and DNA pulse-chase analyses, we identified an anatomical location in the JE that supported both fast- and slow-cycling Wnt-responsive stem cells that contributed to self-renewal of the tissue. Stem cells produced daughter cells with an extraordinarily high rate of turnover that maintained JE integrity for 1.4 y in mice. Blocking cell proliferation via a chemotherapeutic agent 5-fluorouracil (5-Fu) eliminated fast-cycling stem cells, which caused JE degeneration, PDL destruction, and bone resorption. Upon removal of 5-Fu, slow-cycling stem cells regenerated both the structure and barrier function of the JE. Taken together, our studies identified a stem cell population in the JE and have potential clinical implications for prevention and treatment of periodontitis.

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