scholarly journals OC-0583: Intestinal Stem Cells: Modeling of Reserve Stem Cell Population and Volume Effect

2018 ◽  
Vol 127 ◽  
pp. S304-S305
Author(s):  
E. Bahn ◽  
M. Van Heerden ◽  
J. Gueulette ◽  
K. Slabbert ◽  
W. Shaw ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Population ◽  
Volume Effect ◽  
Intestinal Stem Cells ◽  
Stem Cell Population

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 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.

Enhanced Human Hematopoietic Stem Cell Self-Renewal Enabled by Controlling Feedback Signaling From Lineage Committed Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1274-1274
Author(s):  
Elizabeth Csaszar ◽  
Daniel Kirouac ◽  
Mei Yu ◽  
Caryn Ito ◽  
Peter W. Zandstra
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Cell Population ◽  
Ex Vivo ◽  
Stem Cell Population ◽  
Fed Batch ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Cell Numbers

Abstract Abstract 1274 Clinical outcomes of hematopoietic stem cell (HSC) transplantation are correlated with infused progenitor cell dose. Limited cell numbers in a typical umbilical cord blood (UCB) unit restricts the therapeutic potential of UCB and motivates ex vivo expansion of these cells. Strategies to grow HSCs have relied on the supplement of molecules acting directly on the stem cell population; however, in all cases, sustained HSC growth is limited by the concurrent growth of more mature cells and their endogenously produced inhibitory signaling factors. Despite increasing evidence for the important role of intercellular (between cell) communication networks, the identity and impact of non-stem cell autonomous feedback signaling remains poorly understood. Simultaneous kinetic tracking of more than 30 secreted factors produced during UCB culture, including TGF-b1, MIP-1b, and MCP-1, in combination with computational simulations of cell population dynamics, enabled us to develop a global control strategy predicted to reduce inhibitory paracrine signaling and, consequently, increase HSC self-renewal. By maintaining endogenously produced ligands at specified levels using a tuneable fed-batch (automated media dilution) strategy, we achieved significant improvements in expansions of total cell numbers (∼180-fold), CD34+ cells (∼80-fold), and NOD/SCID/IL-2Rgc-null (NSG) repopulating cells (∼11-fold, detected at limiting dilution). The fed-batch strategy has been integrated into an automated bioreactor, allowing for the generation of a clinically-relevant cell product after 12 days of culture, with minimal user manipulation. As this strategy targets the HSC environment and not the stem cells directly, it has the ability to act in combination with other expansion strategies to produce synergistic results. Unexpectedly, supplementation of the soluble protein, TAT-HOXB4, to the system, yielded the expected boost in progenitor expansion only in “sub-optimal” control conditions but not in the fed-batch system. Hypothesizing that the efficacy of HOXB4 may be dependent on the skewing of supportive vs. non-supportive cell populations, and the consequent impact of paracrine ligand production, we performed kinetic tracking of 20 hematopoietic cell types during several supportive (fed-batch, HOXB4 supplemented, Notch ligand Delta1 supplemented) vs. non-supportive (control) cultures. Meta analysis of these data revealed a non-autonomous link between HOXB4, increased megakaryocyte production, and stem cell proliferation, as well as between Notch delta-1 ligand, decreased myeloid cell production, and a decrease in the growth inhibition of stem cells. These predictions have been experimentally validated using co-cultures of sorted purified HSCs and CD41+ megakaryocykes and CD14+ monocytes. Our results identify complex connections between mature cell lineages and stem cell fate decisions and we expect to report a direct link between cell-cell interactions emerging from culture manipulations and the resulting impact on HSC self-renewal. Collectively, these studies support a dominant role for non-stem cell autonomous feedback signaling in the regulation of HSC self-renewal. Overcoming cell non-autonomous inhibition of HSC self-renewal has allowed for novel strategies to enhance HSC numbers ex vivo, thereby facilitating the production of clinically relevant quantities of stem and progenitor cells and enabling more effective strategies to treat hematologic disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Dental pulp pluripotent-like stem cells (DPPSC), a new stem cell population with chromosomal stability and osteogenic capacity for biomaterials evaluation

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Raquel Núñez-Toldrà ◽  
Ester Martínez-Sarrà ◽  
Carlos Gil-Recio ◽  
Miguel Ángel Carrasco ◽  
Ashraf Al Madhoun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Population ◽  
Dental Pulp ◽  
Stem Cell Population ◽  
Chromosomal Stability

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 Phenotypic and Functional Changes Induced at the Clonal Level in Hematopoietic Stem Cells After 5-Fluorouracil Treatment

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3596-3606 ◽  
Author(s):  
Troy D. Randall ◽  
Irving L. Weissman
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Cell Population ◽  
Stem Cell Population ◽  
Normal Bone Marrow ◽  
Hematopoietic Stem ◽  
Normal Bone

Abstract A significant fraction of hematopoietic stem cells (HSCs) have been shown to be resistant to the effects of cytotoxic agents such as 5-fluorouracil (5-FU), which is thought to eliminate many of the rapidly dividing, more committed progenitors in the bone marrow and to provide a relatively enriched population of the most primitive hematopoietic progenitor cells. Although differences between 5-FU–enriched progenitor populations and those from normal bone marrow have been described, it remained unclear if these differences reflected characteristics of the most primitive stem cells that were revealed by 5-FU, or if there were changes in the stem-cell population itself. Here, we have examined some of the properties of the stem cells in the bone marrow before and after 5-FU treatment and have defined several activation-related changes in the stem-cell population. We found that long-term reconstituting stem cells decrease their expression of the growth factor receptor c-kit by 10-fold and increase their expression of the integrin Mac-1 (CD11b). These changes begin as early as 24 hours after 5-FU treatment and are most pronounced within 2 to 3 days. This activated phenotype of HSCs isolated from 5-FU–treated mice is similar to the phenotype of stem cells found in the fetal liver and to the phenotype of transiently repopulating progenitors in normal bone marrow. We found that cell cycle is induced concomitantly with these physical changes, and within 2 days as many as 29% of the stem-cell population is in the S/G2/M phases of the cell cycle. Furthermore, when examined at a clonal level, we found that 5-FU did not appear to eliminate many of the transient, multipotent progenitors from the bone marrow that were found to be copurified with long-term repopulating, activated stem cells. These results demonstrate the sensitivity of the hematopoietic system to changes in its homeostasis and correlate the expression of several important surface molecules with the activation state of HSCs.

ROS activated prodrug for ALDH overexpressed cancer stem cells

2021 ◽  
Author(s):  
Miae Won ◽  
Ji Hyeon Kim ◽  
Myung Sun Ji ◽  
Jong Seung Kim
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Cell Population ◽  
Stem Cell Population ◽  
Cancer Stem Cell Population

We developed a prodrug (DE-CPT) that efficiently decreases the cancer stem cell population and kills the cancer cells by ROS activation.

Differential Expression of SLAM Family Receptor Markers in Normal Human Hematopoietic Stem Cells and Their Malignant Counterpart in MDS and AML.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1897-1897
Author(s):  
Ramon V. Tiu ◽  
Jennifer J. Powers ◽  
Abdo Haddad ◽  
Ying Jiang ◽  
Jaroslaw P. Maciejewski
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Cell Population ◽  
Stem Cell Population ◽  
Leukemic Stem Cell ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Slam Family

Abstract Members of the signaling lymphocytic activation molecule (SLAM) family, including CD150, CD48 and CD244, were shown to precisely distinguish more committed lineage restricted progenitor cells from pluripotent and multipotent murine hematopoietic stem cells (HSC; Kiel et al; 2005 Cell). Similar SLAM profiles may also be present on HSC subsets in humans. We hypothesized that these SLAM markers may be indicators not only of stem cell potential in normal hematopoiesis but also distinguish a subset of the most immature malignant precursors of leukemia. In agreement with the concept of a “cancer stem cell,” the presence of leukemic stem cell population may be an indicator of important clinical and biological properties. We first tested the distribution of CD150, CD48 and CD244 antigens on human CD34+ cells derived from 7 control individuals using 4-color flow cytometry. CD34+ cells were measured in the blast gate based on side scatter and CD45 expression. Within CD34+ blasts, expression of CD48, CD150, and CD244 was detected on 16.71%±9.69, 6.53%±2.93, and 26.92%±6.95 of cells respectively. Subsequently, we investigated SLAM expression in 9 immature leukemic cell lines, including KG-1, K562, U937, HEL, HL60, MKN-95, NB-4, Kasumi and UT7, and found increased expression of SLAM markers in KG-1 (CD48+, CD150+, CD244+) and Kasumi (CD48−, CD150−, CD244+). Consequently, none of the leukemic cells showed pluripotent/multipotent SLAM profiles. We then compared the SLAM marker expression on blasts from patients with AML and MDS with that of CD34+ cells from normal controls. We studied a total of 28 patients: 11 MDS (2 low grade, 5 advanced MDS, 3 MDS/MPD overlap) and 10 AML (FAB: 3 M1, 2 M2, 1 M3, 2 M4/M4E0 and 2 M6). In our cohort, 8/10 AML patients expressed one of the three SLAM markers; 6/10 were CD150−CD48−CD244+ (63.57%±6.96) and 2/10 were CD150+CD48−CD244−(46%±10.96) suggestive of the presence of either pluripotent or multipotent leukemic stem cell phenotype. In the MDS cohort, 8/11 patients expressed one of three SLAM markers, 7/11 were CD150−CD48−CD244+ (41.21% ± 8.9) and 1/11 were CD150+CD48−CD244− (1.26%±0.59) again consistent with a profile derived from either pluripotent or multipotent stem cells. None of the MDS and AML patients had either co-expression of CD244 and CD48 or increased expression of CD48 alone. Two of the M1 type AML patients with CD150−CD48−CD244+ phenotype received prior chemotherapy and achieved complete remission on bone marrow biopsy and flow cytometry using traditional blast markers. In some, we conclude that the SLAM receptor markers may be associated with certain types of leukemic blasts and may be useful in the identification of leukemic stem cell population in both MDS and AML.

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