scholarly journals A comprehensive conceptual and computational dynamics framework for Autonomous Regeneration Systems

2019 ◽  
Author(s):  
Tran Nguyen Minh-Thai ◽  
Sandhya Samarasinghe ◽  
Michael Levin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Damage Detection ◽  
Cell Damage ◽  
Entropy Change ◽  
Cell Network ◽  
Computational Dynamics ◽  
Differentiated Cells ◽  
Tissue Structures ◽  
Pattern Information

AbstractThis paper presents a new conceptual and computational dynamics framework for damage detection and regeneration in multicellular structures similar to living animals. The model uniquely achieves complete and accurate regeneration from any damage anywhere in the system. We demonstrated the efficacy of the proposed framework on an artificial organism consisting of three tissue structures corresponding to the head, body and tail of a worm. Each structure consists of a stem cell surrounded by a tissue of differentiated cells. We represent a tissue as an Auto-Associative Neural Network (AANN) with local interactions and stem cells as a self-repair network with long-range interactions. We also propose another new concept, Information Field which is a mathematical abstraction over traditional components of tissues, to keep minimum pattern information of the tissue structures to be accessed by stem cells in extreme cases of damage. Through entropy, a measure of communication between a stem cell and differentiated cells, stem cells monitor the tissue pattern integrity, violation of which triggers damage detection and tissue repair. Stem cell network monitors its state and invokes stem cell repair in the case of stem cell damage. The model accomplishes regeneration at two levels: In the first level, damaged tissues with intact stem cells regenerate themselves. Here, stem cell identifies entropy change and finds the damage and regenerates the tissue in collaboration with the AANN. In the second level, involving missing whole tissues and stem cells, the remaining stem cell(s) access the information field to restore the stem cell network and regenerate missing tissues. In the case of partial tissue damage with missing stem cells, the two levels collaborate to accurately restore the stem cell network and tissues. This comprehensive hypothetical framework offers a new way to conceptualise regeneration for better understanding the regeneration processes in living systems. It could also be useful in biology for regenerative medicine and in engineering for building self-repairing biobots.

Amniotic Stem Cell-Conditioned Media for the Treatment of Nerve and Muscle Pathology: A Systematic Review

2021 ◽  
Author(s):  
Chukwuweike Gwam ◽  
Ahmed Emara ◽  
Nequesha Mohamed ◽  
Noor Chughtai ◽  
Johannes Plate ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tissue Regeneration ◽  
Cell Damage ◽  
Conditioned Media ◽  
Nerve Tissue ◽  
Muscle Pathology ◽  
Loss Of Function ◽  
Cell Based Therapy

Muscle and nerve tissue damage can elicit a significant loss of function and poses as a burden for patients and healthcare providers. Even for tissues, such as the peripheral nerve and skeletal muscle, that harbor significant regenerative capacity, innate regenerative processes often lead to less than optimal recovery and residual loss of function. The reasons for poor regeneration include significant cell damage secondary to oxidative stress, poor recruitment of resident stem cells, and an unfavorable microenvironment for tissue regeneration. Stem cell-based therapy was once thought as a potential therapy in tissue regeneration, due to its self-renewal and multipotent capabilities. Early advocates for cellular-based therapy pointed to the pluripotent nature of stem cells, thus eluding to its ability to differentiate into resident cells as the source of its regenerative capability. However, increasing evidence has revealed a lack of engraftment and differentiation of stem cells, thereby pointing to stem cell paracrine activity as being responsible for its regenerative potential. Stem cell-conditioned media houses biomolecular factors that portray significant regenerative potential. Amniotic-derived stem cell-conditioned media (AFS-CM) has been of particular interest because of its ease of allocation and in vitro culture. The purpose of this review is to report the results of studies that assess the role of AFS-CM for nerve and muscle conditions. In this review, we will cover the effects of AFS-CM on cellular pathways, genes, and protein expression for different nerve and muscle cell types.

scholarly journals me31B regulates stem cell homeostasis by preventing excess dedifferentiation in the Drosophila male germline

2021 ◽  
Author(s):  
Lindy Jensen ◽  
Zsolt G. Venkei ◽  
George J. Watase ◽  
Bitarka Bisai ◽  
Scott Pletcher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Critical Role ◽  
Stem Cell Population ◽  
Germline Stem Cells ◽  
Cell Identity ◽  
Stem Cell Maintenance ◽  
Differentiated Cells ◽  
Male Germline ◽  
Elevated Frequency

Tissue-specific stem cells maintain tissue homeostasis by providing a continuous supply of differentiated cells throughout the life of organisms. Differentiated/differentiating cells can revert back to a stem cell identity via dedifferentiation to help maintain the stem cell pool beyond the lifetime of individual stem cells. Although dedifferentiation is important to maintain the stem cell population, it is speculated to underlie tumorigenesis. Therefore, this process must be tightly controlled. Here we show that a translational regulator me31B plays a critical role in preventing excess dedifferentiation in the Drosophila male germline: in the absence of me31B, spermatogonia (SGs) dedifferentiate into germline stem cells (GSCs) at a dramatically elevated frequency. Our results show that the excess dedifferentiation is likely due to misregulation of nos, a key regulator of germ cell identity and GSC maintenance. Taken together, our data reveal negative regulation of dedifferentiation to balance stem cell maintenance with differentiation.

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 Mammalian genes induce partially reprogrammed pluripotent stem cells in non-mammalian vertebrate and invertebrate species

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Ricardo Antonio Rosselló ◽  
Chun-Chun Chen ◽  
Rui Dai ◽  
Jason T Howard ◽  
Ute Hochgeschwender ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Mammalian Species ◽  
Embryonic Stem ◽  
Model Organisms ◽  
Differentiated Cells ◽  
Transcription Factor Genes ◽  
Induced Pluripotent

Cells are fundamental units of life, but little is known about evolution of cell states. Induced pluripotent stem cells (iPSCs) are once differentiated cells that have been re-programmed to an embryonic stem cell-like state, providing a powerful platform for biology and medicine. However, they have been limited to a few mammalian species. Here we found that a set of four mammalian transcription factor genes used to generate iPSCs in mouse and humans can induce a partially reprogrammed pluripotent stem cell (PRPSCs) state in vertebrate and invertebrate model organisms, in mammals, birds, fish, and fly, which span 550 million years from a common ancestor. These findings are one of the first to show cross-lineage stem cell-like induction, and to generate pluripotent-like cells for several of these species with in vivo chimeras. We suggest that the stem-cell state may be highly conserved across a wide phylogenetic range.

Maintenance of Pluripotent Stem Cells is Influenced by Ser/Thr Metabolism

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. SCI-43-SCI-43
Author(s):  
Lewis C. Cantley
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Embryonic Stem ◽  
Isocitrate Dehydrogenase 1 ◽  
Advisory Committees ◽  
Metabolic Intermediates ◽  
Stem Cell Maintenance ◽  
Differentiated Cells ◽  
Methylation Of Dna

Abstract Recent studies have suggested not only that stem cells have different metabolic requirements than terminally differentiated cells, but also that metabolic intermediates may play a role in the maintenance of stem cells. It has long been clear that changes in acetylation and methylation of histones, as well as methylation of DNA play critical roles in deciding cell fate. The availability of critical intermediates in metabolism, especially S-adenosylmethionine (SAM), acetyl-CoA, nicotinamide adenine dinucleotide (NAD) and a-ketoglutarate play critical roles in modulating acetylation and methylation of histones and methylation of DNA. In the course of evaluating an unusual requirement of threonine (Thr) for the growth of murine embryonic stem cells, we found that metabolism of Thr to glycine (Gly) and the subsequent use of the methyl group of Gly for converting homocysteine to methionine is critical for maintaining high levels of SAM and low levels of S-adenosyl-homocysteine. Importantly, depletion of Thr from the media resulted in decreased tri-methylation of histone H3 lysine-4 (H3K4me3), leading to slowed growth and increased differentiation. Thus, abundance of SAM appears to influence H3K4me3, providing a possible mechanism by which modulation of a metabolic pathway might influence stem cell fate. Demethylation of histones and DNA can also be controlled by metabolic intermediates. Mutated forms of isocitrate dehydrogenase 1 (IDH1) and IDH2 that drive acute myeloid leukemia (AML) and other cancers, produce an oncometabolite (2-hydrogyglutarate) that can compete with the a-ketoglutarate requirement for enzymes involved in hydroxy-methylation and subsequent demethylation of DNA and histones. Recent studies indicate that 2-hydroxyglutarate plays a role in blocking differentiation of cancer cells. These and other observations linking intermediates in metabolism to stem cell maintenance will be discussed. Disclosures Cantley: Agios Pharmaceuticals: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.

Designing and Engineering Stem Cell Niches

MRS Bulletin ◽  
2010 ◽  
Vol 35 (8) ◽  
pp. 591-596 ◽  
Author(s):  
Ana I. Teixeira ◽  
Ola Hermanson ◽  
Carsten Werner
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Chemical Engineering ◽  
Polyglycolic Acid ◽  
Differentiated Cells ◽  
Extracellular Matrix Components ◽  
Stem Cell Niches

AbstractStem cells have received a lot of attention due to great promises in medical treatment, for example, by replacing lost and sick cells and re-constituting cell populations. There are several classes of stem cells, including embryonic, fetal, and adult tissue specific. More recently, the generation of so-called induced pluripotent stem (iPS) cells from differentiated cells has been established. Common criteria for all types of stem cells include their ability to self-renew and to retain their ability to differentiate in response to specific cues. These characteristics, as well as the instructive steering of the cells into differentiation, are largely dependent on the microenvironment surrounding the cells. Such “stem cell friendly” microenvironments, provided by structural and biochemical components, are often referred to as niches. Biomaterials offer attractive solutions to engineer functional stem cell niches and to steer stem cell state and fatein vitroas well asin vivo. Among materials used so far, promising results have been achieved with low-toxicity and biodegradable polymers, such as polyglycolic acid and related materials, as well as other polymers used as structural “scaffolds” for engineering of extracellular matrix components. To improve the efficiency of stem cell control and the design of the biomaterials, interfaces among stem cell research, developmental biology, regenerative medicine, chemical engineering, and materials research are rapidly developing. Here we provide an introduction to stem cell biology and principles of niche engineering and give an overview of recent advancements in stem cell niche engineering from two stem cell systems—blood and brain.

scholarly journals Serum-Free Manufacturing of Mesenchymal Stem Cell Tissue Rings Using Human-Induced Pluripotent Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Tackla S. Winston ◽  
Kantaphon Suddhapas ◽  
Chenyan Wang ◽  
Rafael Ramos ◽  
Pranav Soman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Culture Conditions ◽  
Serum Free ◽  
Differentiated Cells ◽  
Induced Pluripotent

Combination of stem cell technology and 3D biofabrication approaches provides physiological similarity to in vivo tissues and the capability of repairing and regenerating damaged human tissues. Mesenchymal stem cells (MSCs) have been widely used for regenerative medicine applications because of their immunosuppressive properties and multipotent potentials. To obtain large amount of high-quality MSCs without patient donation and invasive procedures, we differentiated MSCs from human-induced pluripotent stem cells (hiPSC-MSCs) using serum-free E6 media supplemented with only one growth factor (bFGF) and two small molecules (SB431542 and CHIR99021). The differentiated cells showed a high expression of common MSC-specific surface markers (CD90, CD73, CD105, CD106, CD146, and CD166) and a high potency for osteogenic and chondrogenic differentiation. With these cells, we have been able to manufacture MSC tissue rings with high consistency and robustness in pluronic-coated reusable PDMS devices. The MSC tissue rings were characterized based on inner diameter and outer ring diameter and observed cell-type-dependent tissue contraction induced by cell-matrix interaction. Our approach of simplified hiPSC-MSC differentiation, modular fabrication procedure, and serum-free culture conditions has a great potential for scalable manufacturing of MSC tissue rings for different regenerative medicine applications.

Stem Cell-Based Personalized Medicine

2012 ◽  
pp. 1855-1866
Author(s):  
Alessandro Prigione
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Personalized Medicine ◽  
Regenerative Medicine ◽  
Cell Types ◽  
Research Field ◽  
Cellular Reprogramming ◽  
Differentiated Cells ◽  
New Therapeutic Approaches

Regenerative medicine is a rapidly evolving research field whose main aims are to provide new therapeutic approaches and to repair or replace injured tissues with functional cells derived from stem cells. In the past few years, research breakthroughs have revolutionized the field by showing that all somatic cells have the potential to re-acquire stem cell-like properties. Thus, it appears possible to generate relevant cell types starting from cells easily obtained from affected individuals. The obtained differentiated cells could eventually serve as in vitro tools for the study of disease-associated mechanisms and for performing customized drug screenings. Moreover, in the context of cellular transplantation, these cells represent the ideal cell source given that they posses the same genetic code and thus will avoid the occurrence of unwanted immune reactions. Overall, this revolutionary technique called cellular reprogramming might provide substantial support for the future development of personalized medicine. In this chapter, I describe the recent advances in the field of stem cell-based regenerative medicine applications. Parkinson’s disease is chosen as a paradigmatic example in which the use of stem cells for study and therapy could have a relevant impact and potentially represent a future cure for this debilitating disorder.

Mechanical Regulation of Stem Cell Proliferation and Fate Decisions by their Differentiated Daughters

2020 ◽  
Author(s):  
Wenxiu Ning ◽  
Andrew Muroyama ◽  
Hua Li ◽  
Terry Lechler
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Epidermal Keratinocytes ◽  
Stem Cell Proliferation ◽  
Differentiated Cells ◽  
Basal Progenitor ◽  
Cell Niche ◽  
And Migration ◽  
Tissue Tension

AbstractBasal stem cells fuel development, homeostasis, and regeneration of the epidermis. The proliferation and fate decisions of these cells are highly regulated by their microenvironment, including the basement membrane and underlying mesenchymal cells. Basal progenitors give rise to differentiated progeny that serve an essential role in generating the epidermal barrier. Here, we present data that differentiated progeny also regulate the proliferation, differentiation, and migration of basal progenitor cells. Using two distinct mouse lines, we found that increasing contractility of differentiated cells resulted in non-cell autonomous hyperproliferation of stem cells and prevented their commitment to a hair follicle lineage. These phenotypes were rescued by pharmacological inhibitors of contractility. Live-imaging revealed that increasing the contractility of differentiated cells resulted in stabilization of adherens junctions and impaired movement of basal progenitors during hair placode morphogenesis, as well as a defect in migration of melanoblasts. These data suggest that intra-tissue tension regulates stem cell proliferation, fate decisions and migration, similar to the known roles of extracellular matrix rigidity. Additionally, this work demonstrates that differentiated epidermal keratinocytes are a component of the stem cell niche that regulates development and homeostasis of the skin.

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