scholarly journals Stem cells in the adult pancreas and liver

2007 ◽  
Vol 404 (2) ◽  
pp. 169-178 ◽  
Author(s):  
Zoë D. Burke ◽  
Shifaan Thowfeequ ◽  
Macarena Peran ◽  
David Tosh
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Liver Failure ◽  
Adult Stem Cells ◽  
Cellular Therapy ◽  
Cell Types ◽  
Cell Compartment ◽  
Stem Cell Compartment ◽  
Undifferentiated Cells

Stem cells are undifferentiated cells that can self-renew and generate specialized (functional) cell types. The remarkable ability of stem cells to differentiate towards functional cells makes them suitable modalities in cellular therapy (which means treating diseases with the body's own cells). Potential targets for cellular therapy include diabetes and liver failure. However, in order for stem cells to be clinically useful, we must learn to identify them and to regulate their differentiation. We will use the intestine as a classical example of a stem cell compartment, and then examine the evidence for the existence of adult stem cells in two endodermally derived organs: pancreas and liver. We will review the characteristics of the putative stem cells in these tissues and the transcription factors controlling their differentiation towards functional cell types.

Controlling the Stem Cell Compartment and Regeneration In Vivo: The Role of Pluripotency Pathways

2012 ◽  
Vol 92 (1) ◽  
pp. 75-99 ◽  
Author(s):  
Kirsty Greenow ◽  
Alan R. Clarke
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem ◽  
Cell Types ◽  
Dark Side ◽  
Cell Compartment ◽  
Pluripotent State ◽  
Stem Cell Compartment

Since the realization that embryonic stem cells are maintained in a pluripotent state through the interplay of a number of key signal transduction pathways, it is becoming increasingly clear that stemness and pluripotency are defined by the complex molecular convergence of these pathways. Perhaps this has most clearly been demonstrated by the capacity to induce pluripotency in differentiated cell types, so termed iPS cells. We are therefore building an understanding of how cells may be maintained in a pluripotent state, and how we may manipulate cells to drive them between committed and pluripotent compartments. However, it is less clear how cells normally pass in and out of the stem cell compartment under normal and diseased physiological states in vivo, and indeed, how important these pathways are in these settings. It is also clear that there is a potential “dark side” to manipulating the stem cell compartment, as deregulation of somatic stem cells is being increasingly implicated in carcinogenesis and the generation of “cancer stem cells.” This review explores these relationships, with a particular focus on the role played by key molecular regulators of stemness in tissue repair, and the possibility that a better understanding of this control may open the door to novel repair strategies in vivo. The successful development of such strategies has the potential to replace or augment intervention-based strategies (cell replacement therapies), although it is clear they must be developed with a full understanding of how such approaches might also influence tumorigenesis.

scholarly journals FGF10 maintains stem cell compartment in developing mouse incisors

Development ◽  
2002 ◽  
Vol 129 (6) ◽  
pp. 1533-1541 ◽  
Author(s):  
Hidemitsu Harada ◽  
Takashi Toyono ◽  
Kuniaki Toyoshima ◽  
Masahiro Yamasaki ◽  
Nobuyuki Itoh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Expression Patterns ◽  
Stem Cell Population ◽  
Cell Compartment ◽  
Stem Cell Compartment ◽  
Dental Epithelium ◽  
Mouse Incisor ◽  
Induced Apoptosis

Mouse incisors are regenerative tissues that grow continuously throughout life. The renewal of dental epithelium-producing enamel matrix and/or induction of dentin formation by mesenchymal cells is performed by stem cells that reside in cervical loop of the incisor apex. However, little is known about the mechanisms of stem cell compartment formation. Recently, a mouse incisor was used as a model to show that fibroblast growth factor (FGF) 10 regulates mitogenesis and fate decision of adult stem cells. To further illustrate the role of FGF10 in the formation of the stem cell compartment during tooth organogenesis, we have analyzed incisor development in Fgf10-deficient mice and have examined the effects of neutralizing anti-FGF10 antibody on the developing incisors in organ cultures. The incisor germs of FGF10-null mice proceeded to cap stage normally. However, at a later stage, the cervical loop was not formed. We found that the absence of the cervical loop was due to a divergence in Fgf10 and Fgf3 expression patterns at E16. Furthermore, we estimated the growth of dental epithelium from incisor explants of FGF10-null mice by organ culture. The dental epithelium of FGF10-null mice showed limited growth, although the epithelium of wild-type mice appeared to grow normally. In other experiments, a functional disorder of FGF10, caused by a neutralizing anti-FGF10 antibody, induced apoptosis in the cervical loop of developing mouse incisor cultures. However, recombinant human FGF10 protein rescued the cervical loop from apoptosis. Taken together, these results suggest that FGF10 is a survival factor that maintains the stem cell population in developing incisor germs.

Types of Stem Cells Used in US-Based Clinical Trials between 1999 and 2014

2021 ◽  
Vol 26 ◽  
pp. 169-191
Author(s):  
Emma E. Redfield ◽  
Erin K. Luciano ◽  
Monica J. Sewell ◽  
Lucas A. Mitzel ◽  
Isaac J. Sanford ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
The Us ◽  
Health Database ◽  
Induced Pluripotent

This study looks at the number of clinical trials involving specific stem cell types. To our knowledge, this has never been done before. Stem cell clinical trials that were conducted at locations in the US and registered on the National Institutes of Health database at ‘clinicaltrials.gov’ were categorized according to the type of stem cell used (adult, cancer, embryonic, perinatal, or induced pluripotent) and the year that the trial was registered. From 1999 to 2014, there were 2,357 US stem cell clinical trials registered on ‘clinicaltrials.gov,’ and 89 percent were from adult stem cells and only 0.12 percent were from embryonic stem cells. This study concludes that embryonic stem cells should no longer be used for clinical study because of their irrelevance, moral questions, and induced pluripotent stem cells.

scholarly journals The Epidermal Stem Cell Compartment: Variation in Expression Levels of E–Cadherin and Catenins Within the Basal Layer of Human Epidermis

1997 ◽  
Vol 45 (6) ◽  
pp. 867-874 ◽  
Author(s):  
Jean-Pierre Molès ◽  
Fiona M. Watt
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Basal Layer ◽  
Human Epidermis ◽  
Proliferative Potential ◽  
Stem Cell Markers ◽  
Cell Compartment ◽  
Stem Cell Compartment ◽  
E Cadherin ◽  
Cell Cell

The basal layer of the epidermis contains two types of proliferating keratinocyte: stem cells, with high proliferative potential, and transit amplifying cells, which are destined to undergo terminal differentiation after a few rounds of division. It has been shown previously that two- to three-fold differences in the average staining intensity of fluorescein-conjugated antibodies to β1 integrin subunits reflect profound differences in the proliferative potential of keratinocytes, with integrin-bright populations being enriched for stem cells. In the search for additional stem cell markers, we have stained sections of normal human epidermis with antibodies to proteins involved in intercellular adhesion and quantitated the fluorescence of individual cell-cell borders. In the basal layer, patches of brightly labeled cells were detected with antibodies to E-cadherin, β-catenin, and γ-catenin, but not with antibodies to P-cadherin, α-catenin, or with pan-desmocollin and pan-desmoglein antibodies. In the body sites examined, palm and foreskin, integrinbright regions were strongly labeled for γ-catenin and weakly labeled for E-cadherin and β-catenin. Our data suggest that there are gradients of both cell-cell and cell-extracellular matrix adhesiveness within the epidermal basal layer and that the levels of E-cadherin and of β-and γ-catenin may provide markers for the stem cell compartment, stem cells expressing relatively higher levels of γ-catenin and lower levels of E-cadherin and β-catenin than other basal keratinocytes.

Very small embryonic-like stem cells as a novel developmental concept and the hierarchy of the stem cell compartment

2014 ◽  
Vol 59 (2) ◽  
pp. 273-280 ◽  
Author(s):  
Mariusz Z. Ratajczak ◽  
Krzysztof Marycz ◽  
Agata Poniewierska-Baran ◽  
Katarzyna Fiedorowicz ◽  
Monika Zbucka-Kretowska ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Compartment ◽  
Stem Cell Compartment

scholarly journals Pluripotential stem cell differentiation in hemopoietic colonies

Blood ◽  
1976 ◽  
Vol 47 (2) ◽  
pp. 315-323 ◽  
Author(s):  
RL DeGowin ◽  
DP Gibson
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mononuclear Cells ◽  
Tritiated Thymidine ◽  
Myeloid Cells ◽  
Stem Cell Differentiation ◽  
Lymphoid Cells ◽  
Cell Compartment ◽  
Split Dose ◽  
Stem Cell Compartment

Abstract To determine if mononuclear cells proliferating in murine hemopoietic spleen colonies were pluripotential in addition to possessing kinetic features of stem cells, we performed sequential studies of mice during their recovery from a split-dose irradiation regimen of 850 roentgens leg shielded-3-hr interval-850 roentgens leg irradiated (850R L.S. 3- L.I.). Injecting tritiated thymidine during stem cell compartment repletion 3 and 4 days after 850R L.S. 3- L.I. resulted in heavily labeled mononuclear cells resembling medium to large leptochromatic lymphocytes in the portion of spleen removed an hour after injection. The splenic remnant obtained from the same mouse 24–48 hr later contained lightly labeled erythroblasts, myeloid cells, and lymphoid cells. Grain counts suggested that erythroblasts and their precursors had undergone about four divisions, myeloid cells and their precursors two to three divisions, and lymphoid cells and their precursors two to three divisions during the 48-hr period. Similar studies in plethoric mice demonstrated the labeling of mononuclear cells on day 4 and their differentiation to myeloid and lymphoid cells by day 6. This finding confirmed that the labeled mononuclear cells were not exclusively erythroblast progenitors. On the basis of these and previous studies of post-irradiation survival and erythropoietic recovery, we conclude that these endogenous monomuclear cells, which resemble medium to large leptochromatic lymphocytes and replicate during stem cell compartment repletion, are pluripotential hemopoietic stem cells.

scholarly journals Exploring the Most Promising Stem Cell Therapy in Liver Failure: A Systematic Review

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Jeanne AdiwinataPawitan
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Liver Failure ◽  
Stem Cell Therapy ◽  
Adult Stem Cells ◽  
Cochrane Library ◽  
Safety And Efficacy ◽  
Alternative Approaches

Background. Alternative approaches to transplantation for liver failure are needed. One of the alternative approaches is stem cell therapy. However, stem cell therapy in liver failure is not standardized yet, as every centre have their own methods. This systematic review is aimed at compiling and analyzing the various studies that use stem cells to treat liver failure, to get an insight into potential protocols in terms of safety and efficacy by comparing them to controls. Methods. This systematic review was done according to PRISMA guidelines and submitted for registration in PROSPERO (registration number CRD42018106119). All published studies in PubMed/MEDLINE and Cochrane Library, using key words: “human” and “stem cell” AND “liver failure” on 16th June 2018, without time restriction. In addition, relevant articles that are found during full-text search were added. Inclusion criteria included all original articles on stem cell use in humans with liver failure. Data collected included study type, treatment and control number, severity of disease, concomitant therapy, type and source of cells, passage of cells, dose, administration route, repeats, and interval between repeats, outcomes, and adverse events compared to controls. Data were analyzed descriptively to determine the possible causes of adverse reactions, and which protocols gave a satisfactory outcome, in terms of safety and efficacy. Results. There were 25 original articles, i.e., eight case studies and 17 studies with controls. Conclusion. Among the various adult stem cells that were used in human studies, MSCs from the bone marrow or umbilical cord performed better compared to other types of adult stem cells, though no study showed a complete and sustainable performance in the outcome measures. Intravenous (IV) route was equal to invasive route. Fresh or cryopreserved, and autologous or allogeneic MSCs were equally beneficial; and giving too many cells via intraportal or the hepatic artery might be counterproductive.

scholarly journals Clostridioides difficileinfection damages colonic stem cells via TcdB, impairing epithelial repair and recovery from disease

2020 ◽  
Vol 117 (14) ◽  
pp. 8064-8073 ◽  
Author(s):  
Steven J. Mileto ◽  
Thierry Jardé ◽  
Kevin O. Childress ◽  
Jaime L. Jensen ◽  
Ashleigh P. Rogers ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Disease Recurrence ◽  
Gastrointestinal Infections ◽  
Cell Compartment ◽  
Epithelial Repair ◽  
Epithelial Regeneration ◽  
Clostridioides Difficile ◽  
Stem Cell Compartment ◽  
Colonic Stem Cells

Gastrointestinal infections often induce epithelial damage that must be repaired for optimal gut function. While intestinal stem cells are critical for this regeneration process [R. C. van der Wath, B. S. Gardiner, A. W. Burgess, D. W. Smith,PLoS One8, e73204 (2013); S. Kozaret al.,Cell Stem Cell13, 626–633 (2013)], how they are impacted by enteric infections remains poorly defined. Here, we investigate infection-mediated damage to the colonic stem cell compartment and how this affects epithelial repair and recovery from infection. Using the pathogenClostridioides difficile,we show that infection disrupts murine intestinal cellular organization and integrity deep into the epithelium, to expose the otherwise protected stem cell compartment, in a TcdB-mediated process. Exposure and susceptibility of colonic stem cells to intoxication compromises their function during infection, which diminishes their ability to repair the injured epithelium, shown by altered stem cell signaling and a reduction in the growth of colonic organoids from stem cells isolated from infected mice. We also show, using both mouse and human colonic organoids, that TcdB from epidemic ribotype 027 strains does not require Frizzled 1/2/7 binding to elicit this dysfunctional stem cell state. This stem cell dysfunction induces a significant delay in recovery and repair of the intestinal epithelium of up to 2 wk post the infection peak. Our results uncover a mechanism by which an enteric pathogen subverts repair processes by targeting stem cells during infection and preventing epithelial regeneration, which prolongs epithelial barrier impairment and creates an environment in which disease recurrence is likely.

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