Elimination of both cancer stem cells and progenitor cells as essential for tumor eradication.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22179-e22179
Author(s):  
Creticus Petrov Marak ◽  
Achuta Kumar Guddati
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Progenitor Cells ◽  
Cell System ◽  
Differentiated Cells ◽  
Differentiating Agents ◽  
Stem Cell System ◽  
Tumor Eradication ◽  
Stem Cell Pool

e22179 Background: Cancer stem cells (CSC) have been identified in several malignancies. Elimination of CSCs requires precise identification of markers and development of mechanisms to target them specifically. It is possible that in spite of elimination of CSCs, the tumor may recur. Dedifferentiation of progenitor cells may help replenish cancer stem cells. Methods: A mathematical model of a cancer stem cell system with four layers has been constructed to reflect the hierarchy of cancer stem cells, progenitor cells and, transit-amplifying cells and pre-differentiated cells. This model is constructed in the lines of the phase space model described by Kirkland. Dedifferentiation parameters were introduced to allow for dedifferentiation when the stem cell pool receded below 40% of its normal size. The effects of stem cell antagonists (SCA) and differentiating agents (DA) were simulated to study the perturbations caused by them on the growth of the tumor. Results: SCAs when used alone result in the establishment of a new equilibrium across different layers within the tumor by de-differentiation. DAs which act only on progenitor cells cause an increase in the number of cells in the subsequent layers and contribute to an increase in the size of the tumor. DAs which act only on the pre-differentiated layer of cells move cells from this layer into a terminally differentiated layer of cells which results in a new but lower equilibrium. DAs which act on the progenitor, transit amplifying and pre-differentiated cells cause the establishment of a new equilibrium which is lower than that of all agents which act on individual layers of cells. A combination of an SCA and a DA which acts on multiple layers eliminates the re-establishment of a new equilibrium and leads to decline in cell populations in all the layers, thus reducing the possibility of recurrence. Conclusions: SCAs when used individually are not effective in eliminating the tumor. DAs which act only on progenitor cells can fuel tumor growth but DAs which act on multiple layers have a profound effect in slowing the growth of the tumor but do not eliminate the tumor. This model implies that a combination of an SCA and a DA which acts on multiple layers may have a better chance at eliminating the tumor.

scholarly journals Aging germline stem cells in C. elegans

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 740-740
Author(s):  
E Jane Hubbard
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell System ◽  
Cell Aging ◽  
Germline Stem Cell ◽  
Germline Stem Cells ◽  
C Elegans ◽  
Cell Pool ◽  
Stem Cell System ◽  
Stem Cell Pool

Abstract Failure to maintain stem cells with age is associated with conditions such as tissue degeneration and increased susceptibility to tissue damage. We use the C. elegans germline stem cell system as a model to study stem cell aging. This system combines a well-established model for aging with an accessible stem cell system, providing a unique opportunity to understand how aging influences stem cell dynamics. The germline stem/progenitor pool in in C. elegans becomes depleted over time. At the cellular level, aging influences both the size of the stem cell pool and the proliferation rate of stem cells. The flux of differentiated cells also affects how aging impacts the pool. This depletion is partially alleviated in mutants with reduced insulin/IGF-like signaling via inhibition of the transcription factor DAF-16/FOXO. In this role, DAF-16 does not act in the germ line, and its anatomical requirements are different from its previously described roles in larval germline proliferation, dauer control, and lifespan regulation. We found that DAF-16/FOXO is required in certain somatic cells in the proximal part of the reproductive system to regulate the stem cell pool. We also find that the degree to which various age-defying perturbations affect lifespan does not correlate with their effect on germline stem cell maintenance. We are investigating additional aspects of aging germline stem cells using this system.

scholarly journals miRNA function and modulation in stem cells and cancer stem cells

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Andrew J. DeCastro ◽  
James DiRenzo
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cell Phenotype ◽  
Pluripotent State ◽  
Differentiated Cells ◽  
Non Coding Rnas ◽  
Multicellular Organisms ◽  
Stem Cell Phenotype

AbstractStem cells belong to a unique class of cells that is collectively responsible for the development and subsequent maintenance of all tissues comprising multicellular organisms. These cells possess unique characteristics that allow them to remain in a pluripotent state, while also continuing to generate differentiated cells. microRNAs, a specialized class of non-coding RNAs, are integral components of the network of pathways that modulates this combination of abilities. This review highlights recent discoveries about the roles miRNAs play in governing stem cell phenotype, and discusses the potential therapeutic utility that miRNAs may have in the treatment of multiple diseases. Additionally, it addresses a novel mode of regulation of stem cell phenotype through lincRNA-mediated modulation of select miRNAs, and the role of secreted, stem cell-derived miRNAs in exerting a paracrine influence on surrounding non-stem cells.

scholarly journals Tissue Stem Cells of the Human Vocal Fold Mucosa and Their Stem Cell System

2020 ◽  
Vol 32 (02) ◽  
pp. 93-98
Author(s):  
Kiminori Sato ◽  
Shun-ichi Chitose ◽  
Fumihiko Sato ◽  
Kiminobu Sato ◽  
Takashi Kurita ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Vocal Fold ◽  
Cell System ◽  
Stem Cell System

scholarly journals WUSCHEL acts as an auxin response rheostat to maintain apical stem cells in Arabidopsis

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yanfei Ma ◽  
Andrej Miotk ◽  
Zoran Šutiković ◽  
Olga Ermakova ◽  
Christian Wenzl ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell System ◽  
Auxin Signaling ◽  
Stable Gene ◽  
Stem Cell System ◽  
Plant Stem ◽  
Low Levels ◽  
Stable Gene Expression

Abstract To maintain the balance between long-term stem cell self-renewal and differentiation, dynamic signals need to be translated into spatially precise and temporally stable gene expression states. In the apical plant stem cell system, local accumulation of the small, highly mobile phytohormone auxin triggers differentiation while at the same time, pluripotent stem cells are maintained throughout the entire life-cycle. We find that stem cells are resistant to auxin mediated differentiation, but require low levels of signaling for their maintenance. We demonstrate that the WUSCHEL transcription factor confers this behavior by rheostatically controlling the auxin signaling and response pathway. Finally, we show that WUSCHEL acts via regulation of histone acetylation at target loci, including those with functions in the auxin pathway. Our results reveal an important mechanism that allows cells to differentially translate a potent and highly dynamic developmental signal into stable cell behavior with high spatial precision and temporal robustness.

Advances of Stem Cell Therapy to Treat Heart Failure

Nano LIFE ◽  
2019 ◽  
Vol 09 (03) ◽  
pp. 1941002
Author(s):  
Yanbin Fu ◽  
Zhiying He ◽  
Chao Zhang
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Stem Cell Therapy ◽  
Cell Types ◽  
Differentiated Cells ◽  
Novel Strategy

Stem cell therapy is being developed as a promising novel strategy for the treatment of heart-associated diseases. Several types of cells such as skeletal myoblasts, bone marrow (BM) mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), adipose stem cells (ADSCs), cardiac progenitor cells (CPCs), induced pluripotent stem cells (iPSCs) have been tested in pre-clinical and clinical cardiac repairing models. Fibroblasts, as terminally differentiated cells, could also be trans-differentiated into cardiomyocytes in vitro. In this review, we will summarize the recent advances of cell types, potential applications and challenges of stem cell therapy in the treatment of heart failure.

scholarly journals Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Pedro M. Aponte ◽  
Andrés Caicedo
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Adult Stem Cells ◽  
Future Research ◽  
Differentiated Cells ◽  
Essential Components ◽  
A Cell ◽  
Cell Niche

Stemness combines the ability of a cell to perpetuate its lineage, to give rise to differentiated cells, and to interact with its environment to maintain a balance between quiescence, proliferation, and regeneration. While adult Stem Cells display these properties when participating in tissue homeostasis, Cancer Stem Cells (CSCs) behave as their malignant equivalents. CSCs display stemness in various circumstances, including the sustaining of cancer progression, and the interaction with their environment in search for key survival factors. As a result, CSCs can recurrently persist after therapy. In order to understand how the concept of stemness applies to cancer, this review will explore properties shared between normal and malignant Stem Cells. First, we provide an overview of properties of normal adult Stem Cells. We thereafter elaborate on how these features operate in CSCs. We then review the organization of microenvironment components, which enables CSCs hosting. We subsequently discuss Mesenchymal Stem/Stromal Cells (MSCs), which, although their stemness properties are limited, represent essential components of the Stem Cell niche and tumor microenvironment. We next provide insights of the therapeutic strategies targeting Stem Cell properties in tumors and the use of state-of-the-art techniques in future research. Increasing our knowledge of the CSCs microenvironment is key to identifying new therapeutic solutions.

scholarly journals A Mathematical Model of Average Dynamics in a Stem Cell Hierarchy Suggests the Combinatorial Targeting of Cancer Stem Cells and Progenitor Cells as a Potential Strategy against Tumor Growth

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2590
Author(s):  
Rodolfo Molina-Peña ◽  
Juan Carlos Tudon-Martinez ◽  
Osvaldo Aquines-Gutiérrez
Keyword(s):  
Mathematical Model ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Combination Therapy ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Tumor Relapse ◽  
Differentiated Cells ◽  
P Cells

The cancer stem cell hypothesis states that tumors are maintained by a small subpopulation of stem-like cells, often called cancer stem cells (CSCs) or tumor initiating cells. CSCs can self-renew and give rise to more differentiated cells, which comprise the bulk of the tumor. In addition, CSCs are resistant to conventional therapy, which suggests that they are responsible for tumor relapse. This has led researchers to increase efforts to develop directed therapies against CSCs. However, some experiments in mice have shown that the elimination of CSCs might not ensure tumor eradication. This may be due to different events, such as residual CSCs after treatment, the plasticity of cells within the tumor, the presence of different CSCs having their own hierarchy within the same tumor, and the ability of more differentiated cells to maintain the disease, among others. Trying to decipher this complexity may benefit from dissecting the whole in its parts. Here, we hypothesize that tumor relapse after the selective targeting of CSCs may be due to intermediate progenitor (P) cells that can maintain the tumor volume. In order to support the hypothesis, we implemented a mathematical model derived using pseudo-reactions representing the events of each cell subpopulation within the tumor. We aimed to test if a minimal unidirectional hierarchical model consisting of CSCs, P, and terminally differentiated (D) cells could be adjusted to experimental data for selective CSC targeting. We further evaluated therapies ranging from nonselective to specifically directed and combination therapy. We found that selective killing of the CSC compartment has a delaying effect on the overall exponential tumor growth, but was not able to eliminate the disease. We show that therapy that targets both CSCs and intermediate progenitor (P) cells with a sufficient capacity to proliferate and differentiate could represent a more efficient treatment option for tumor depletion. Testing this hypothesis in vivo may allow us to discriminate within the array of possibilities of tumor relapse, and further open the idea of combination therapy against different subpopulations of tumor cells instead of segregating CSCs and bulk tumor cells.

scholarly journals WUSCHEL acts as a rheostat on the auxin pathway to maintain apical stem cells in Arabidopsis

2018 ◽  
Author(s):  
Yanfei Ma ◽  
Andrej Miotk ◽  
Zoran Šutiković ◽  
Anna Medzihradszky ◽  
Christian Wenzl ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell System ◽  
Auxin Signaling ◽  
Stable Gene ◽  
Stem Cell System ◽  
Plant Stem ◽  
Low Levels ◽  
Stable Gene Expression

ABSTRACTTo maintain the balance between long-term stem cell self-renewal and differentiation, dynamic signals need to be translated into spatially precise and temporally stable gene expression states. In the apical plant stem cell system, local accumulation of the small, highly mobile phytohormone auxin triggers differentiation while at the same time, pluripotent stem cells are maintained throughout the entire life-cycle. We find that stem cells are resistant to auxin mediated differentiation, but require low levels of signaling for their maintenance. We demonstrate that the WUSCHEL transcription factor confers this behavior by rheostatically controlling the auxin signaling and response pathway. Finally, we show that WUSCHEL acts via regulation of histone acetylation at target loci, including those with functions in the auxin pathway. Our results reveal an important mechanism that allows cells to differentially translate a potent and highly dynamic developmental signal into stable cell behavior with high spatial precision and temporal robustness.

scholarly journals Elucidating the identity and behavior of spermatogenic stem cells in the mouse testis

Reproduction ◽  
2012 ◽  
Vol 144 (3) ◽  
pp. 293-302 ◽  
Author(s):  
Shosei Yoshida
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell System ◽  
Tissue Architecture ◽  
Universal Principle ◽  
Single Cell Suspension ◽  
Daughter Cells ◽  
Classical Models ◽  
Stem Cell System ◽  
And Behavior

Spermatogenesis in mice and other mammalians is supported by a robust stem cell system. Stem cells maintain themselves and continue to produce progeny that will differentiate into sperm over a long period. The pioneering studies conducted from the 1950s to the 1970s, which were based largely on extensive morphological analyses, have established the fundamentals of mammalian spermatogenesis and its stem cells. The prevailing so-called Asingle (As) model, which was originally established in 1971, proposes that singly isolated As spermatogonia are in fact the stem cells. In 1994, the first functional stem cell assay was established based on the formation of repopulating colonies after transplantation in germ cell-depleted host testes, which substantially accelerated the understanding of spermatogenic stem cells. However, because testicular tissues are dissociated into single-cell suspension before transplantation, it was impossible to evaluate the As and other classical models solely by this technique. From 2007 onwards, functional assessment of stem cells without destroying the tissue architecture has become feasible by means of pulse-labeling and live-imaging strategies. Results obtained from these experiments have been challenging the classical thought of stem cells, in which stem cells are a limited number of specialized cells undergoing asymmetric division to produce one self-renewing and one differentiating daughter cells. In contrast, the emerging data suggest that an extended and heterogeneous population of cells exhibiting different degrees of self-renewing and differentiating probabilities forms a reversible, flexible, and stochastic stem cell system as a population. These features may lead to establishment of a more universal principle on stem cells that is shared by other systems.

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