scholarly journals Insulin/IGF-1 enhances intestinal epithelial crypt proliferation through PI3K/Akt, and not ERK signaling in obese humans

2018 ◽  
Vol 243 (11) ◽  
pp. 911-916 ◽  
Author(s):  
Weinan Zhou ◽  
Blair M Rowitz ◽  
Megan J Dailey
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Intestinal Epithelial ◽  
Receptor Signaling ◽  
Epithelial Stem Cells ◽  
Cell Niche ◽  
And Function ◽  
Abnormal Tissue

The intestinal epithelium is continuously regenerated through proliferation and differentiation of stem cells located in the intestinal crypts. Obesity affects this process and results in greater stem cell proliferation and altered tissue growth and function. Obesity-induced high levels of insulin and insulin-like growth factor-1 in the stem cell niche are found to impact proliferation in rodents indicating that insulin and insulin-like growth factor-1 receptors may play a role in modulating intestinal epithelial stem cell proliferation. To determine whether insulin or insulin-like growth factor-1 can induce proliferation in human intestinal epithelial stem cells, and if two downstream insulin and insulin-like growth factor-1 receptor signaling pathways, PI3K/Akt and ERK, are involved, we used primary small intestinal epithelial crypts isolated from obese humans and investigated (1) the effect of insulin or insulin-like growth factor-1 on crypt proliferation, and (2) the effect of insulin and insulin-like growth factor-1 signaling inhibitors on insulin or insulin-like growth factor-1-induced proliferation. We found that insulin and insulin-like growth factor-1 enhanced the proliferation of crypt cells, including intestinal epithelial stem cells. Inhibition of the PI3K/Akt pathway attenuated insulin and insulin-like growth factor-1-induced proliferation, but inhibition of the ERK pathway had no effect. These results suggest that the classical metabolic PI3K pathway and not the canonical proliferation ERK pathway is involved in the insulin/insulin-like growth factor-1-induced increase in crypt proliferation in obese humans, which may contribute to abnormal tissue renewal and function. Impact statement This study investigates if insulin or insulin-like growth factor-1 (IGF-1) induces intestinal epithelial proliferation in humans, and if insulin and IGF-1 receptor signaling is involved in this process in obesity. Although obesity-induced high levels of insulin and IGF-1 in the stem cell niche are found to impact the proliferation of intestinal epithelial stem cells in rodents, we are the first to investigate this effect in humans. We found that insulin and IGF-1 enhanced the proliferation of intestinal crypts (including stem cells and other crypt cells) isolated from obese humans, and PI3K/Akt, and not ERK signaling was involved in insulin or IGF-1-induced proliferation. The imbalance in signaling between PI3K/Akt and ERK pathways may point to a pathway-specific impairment in insulin/IGF-1 receptor signaling. We propose that this may contribute to reciprocal relationships between insulin/IGF-1 receptor resistance and intestinal epithelial proliferation that leads to abnormal tissue renewal and function.

Distribution of amniotic stem cells in human term amnion membrane

Microscopy ◽  
2021 ◽  
Author(s):  
Nobuyuki Koike ◽  
Jun Sugimoto ◽  
Motonori Okabe ◽  
Kenichi Arai ◽  
Makiko Nogami ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Markers ◽  
Epithelial Stem Cells ◽  
Human Amnion ◽  
Transporter Protein ◽  
Amniotic Mesenchymal Stem Cells ◽  
Amnion Membrane ◽  
And Function ◽  
A Site

Abstract Amnion membrane studies related to miscarriage have been conducted in the field of obstetrics and gynecology. However, the distribution of stem cells within the amnion and the differences in the properties of each type of stem cells are still not well understood. We address this gap in knowledge in the present study where we morphologically classified the amnion membrane, and we clarified the distribution of stem cells here to identify functionally different amniotic membrane–derived stem cells. The amnion can be divided into a site that is continuous with the umbilical cord (region A), a site that adheres to the placenta (region B), and a site that is located opposite the placenta (region C). We found that human amnion epithelial stem cells (HAECs) that strongly express stem cell markers were abundant in area A. HAEC not only expressesed stem cell-specific surface markers TRA-1-60, Tra-1-81, SSEA4, SSEA3, but was also OCT-3/4 positive and had alkaline phosphatase activity. Human amniotic mesenchymal stem cells expressed KLF-A, OCTA, Oct3/4, c-MYC and Sox2 which is transcription factor. Especially, in regions A and B they have expressed CD73, and the higher expression of BCRP which is drug excretion transporter protein than the other parts. These data suggest that different types of stem cells may have existed in different area. The understanding the relation with characteristics of the stem cells in each area and function would allow for the efficient harvest of suitable HAE and HAM stem cells as using tool for regenerative medicine.

scholarly journals Insulin-like Growth Factor II: An Essential Adult Stem Cell Niche Constituent in Brain and Intestine

2019 ◽  
Vol 12 (4) ◽  
pp. 816-830 ◽  
Author(s):  
Amber N. Ziegler ◽  
Qiang Feng ◽  
Shravanthi Chidambaram ◽  
Jaimie M. Testai ◽  
Ekta Kumari ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Stem Cell Niche ◽  
Adult Stem Cell ◽  
Insulin Like Growth Factor ◽  
Factor Ii ◽  
Cell Niche

scholarly journals Role of Insulin-like Growth Factor 1 Receptor Signaling in Stem Cell Stemness and Therapeutic Efficacy

2018 ◽  
Vol 27 (9) ◽  
pp. 1313-1319 ◽  
Author(s):  
Chiao-Fang Teng ◽  
Long-Bin Jeng ◽  
Woei-Cherng Shyu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Growth Factor ◽  
Therapeutic Efficacy ◽  
Functional Markers ◽  
Insulin Like Growth Factor ◽  
Self Renewal ◽  
Placental Mesenchymal Stem Cells ◽  
Igf1r Signaling

Evidence has emerged that stem cells represent a promising therapeutic tool for tissue engineering and regenerative medicine. Thus, identifying functional markers for selecting stem cells capable of superior self-renewal and pluripotency (or multipotency) and maintaining stem cell identity under appropriate culture conditions are critical for guiding the use of stem cells toward clinical applications. Many investigations have implicated the insulin-like growth factor 1 receptor (IGF1R) signaling in maintenance of stem cell characteristics and enhancement of stem cell therapy efficacy. IGF1R-expressing stem cells display robust pluripotent or multipotent properties. In this review, we summarize the essential roles of IGF1R signaling in self-renewal, pluripotency (or multipotency), and therapeutic efficacy of stem cells, including human embryonic stem cells, neural stem cells, cardiac stem cells, bone marrow mesenchymal stem cells, placental mesenchymal stem cells, and dental pulp mesenchymal stem cells. Modifying IGF1R signaling may thus provide potential strategies for maintaining stem cell properties and improving stem-cell-based therapeutic applications.

scholarly journals Characterization of putative stem cells in isolated human colonic crypt epithelial cells and their interactions with myofibroblasts

2009 ◽  
Vol 296 (2) ◽  
pp. C296-C305 ◽  
Author(s):  
S. Samuel ◽  
R. Walsh ◽  
J. Webb ◽  
A. Robins ◽  
C. Potten ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Epithelial Cells ◽  
Side Population ◽  
Cell Types ◽  
Population Characteristics ◽  
Colonic Crypt ◽  
Epithelial Stem Cells ◽  
Colonic Crypts ◽  
Cell Niche

Colonic epithelial stem cells are believed to be located at the crypt base where they have previously been shown to express musashi-1. The colonic stem cell niche, which includes extracellular matrix and myofibroblasts (together with other cell types), is likely to be important in maintaining the function of the progenitor cells. The aims of our studies were to characterize stem cells in isolated and disaggregated human colonic crypt epithelial cells and investigate their interactions with monolayers of primary human colonic myofibroblasts. In unfractionated preparations of disaggregated colonic crypts, musashi-1 positive cells preferentially adhered to colonic myofibroblasts, despite the presence of excess blocking anti-β1-integrin antibody. These adherent epithelial cells remained viable for a number of days and developed slender processes. Cells with side population characteristics (as demonstrated by ability to expel the dye Hoechst 33342) were consistently seen in the isolated colonic crypt epithelial cells. These side population cells expressed musashi-1, β1-integrin, BerEP4, and CD133. Sorted side population crypt epithelial cells also rapidly adhered to primary colonic myofibroblasts. In conclusion, in preparation of isolated and disaggregated human colonic crypts, cells with stem cell characteristics preferentially adhere to primary human colonic myofibroblasts in a β1-integrin-independent fashion.

scholarly journals The Role of Limbal Epithelial Stem Cells in Regulating Corneal (Lymph)angiogenic Privilege and the Micromilieu of the Limbal Niche following UV Exposure

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
M. Notara ◽  
A. Lentzsch ◽  
M. Coroneo ◽  
C. Cursiefen
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Damage ◽  
Lymphatic Vessels ◽  
Uv Exposure ◽  
Epithelial Stem Cells ◽  
Limbal Epithelium ◽  
Limbal Epithelial Stem Cells ◽  
Cell Niche

The cornea is a clear structure, void of blood, and lymphatic vessels, functioning as our window to the world. Limbal epithelial stem cells, occupying the area between avascular cornea and vascularized conjunctiva, have been implicated in tissue border maintenance, preventing conjunctivalisation and propagation of blood and lymphatic vessels into the cornea. Defects in limbal epithelial stem cells are linked to corneal neovascularisation, including lymphangiogenesis, chronic inflammation, conjunctivalisation, epithelial abnormalities including the presence of goblet cells, breaks in Bowman’s membrane, persistent epithelial defects and ulceration, ocular surface squamous neoplasia, lipid keratopathy, pain, discomfort, and compromised vision. It has been postulated that pterygium is an example of focal limbal deficiency. Previous reports showing changes occurring in limbal epithelium during pterygium pathogenesis suggest that there is a link to stem cell damage. In this light, pterygium can serve as a model disease of UV-induced stem cell damage also characterised by corneal blood and lymphangiogenesis. This review focuses on the role of corneal and limbal epithelial cells and the stem cell niche in maintaining corneal avascularity and corneal immune privilege and how this may be deregulated following UV exposure. We present an overview of the PUBMED literature in the field as well as recent work from our laboratories.

scholarly journals Bi-compartmentalized stem cell organization of the corneal limbal niche

2020 ◽  
Author(s):  
Olivia Farrelly ◽  
Yoko Suzuki-Horiuchi ◽  
Megan Brewster ◽  
Paola Kuri ◽  
Sixia Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Tissue Architecture ◽  
Corneal Regeneration ◽  
Cell Organization ◽  
Cell Niche ◽  
Slow Cycling ◽  
And Function

AbstractStem cells exist in precise locations within tissues, yet how their organization supports tissue architecture and function is poorly understood. The limbus is the presumptive stem cell niche of the corneal epithelium. Here, we visualize the live limbus and track the activity of single stem cells in their native environment by 2-photon microscopy. We identify previously unknown niche compartments and show that long implicated slow-cycling cells form separate lineages in the outer limbus, with only local clonal dynamics. Instead, we find distinct stem cells in the pericorneal limbus to be required for corneal regeneration. Unbiased photolabeling captures their progeny exiting the niche, then moving centripetally in unison before undergoing terminal differentiation. This study demonstrates how a compartmentalized stem cell organization coordinates tissue regeneration.One Sentence SummaryIn vivo live imaging of the regenerating cornea reveals distinct stem cell activities in the limbal niche

scholarly journals Stem Cell Niche Microenvironment: Review

2021 ◽  
Vol 8 (8) ◽  
pp. 108
Author(s):  
Mohamed Abdul-Al ◽  
George Kumi Kyeremeh ◽  
Morvarid Saeinasab ◽  
Saeed Heidari Keshel ◽  
Farshid Sefat
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Corneal Epithelium ◽  
Stem Cell Niche ◽  
Epithelial Stem Cells ◽  
Self Renewal ◽  
Human Corneal Epithelium ◽  
Limbal Epithelial Stem Cells ◽  
Cell Niche

The cornea comprises a pool of self-regenerating epithelial cells that are crucial to preserving clarity and visibility. Limbal epithelial stem cells (LESCs), which live in a specialized stem cell niche (SCN), are crucial for the survival of the human corneal epithelium. They live at the bottom of the limbal crypts, in a physically enclosed microenvironment with a number of neighboring niche cells. Scientists also simplified features of these diverse microenvironments for more analysis in situ by designing and recreating features of different SCNs. Recent methods for regenerating the corneal epithelium after serious trauma, including burns and allergic assaults, focus mainly on regenerating the LESCs. Mesenchymal stem cells, which can transform into self-renewing and skeletal tissues, hold immense interest for tissue engineering and innovative medicinal exploration. This review summarizes all types of LESCs, identity and location of the human epithelial stem cells (HESCs), reconstruction of LSCN and artificial stem cells for self-renewal.

scholarly journals Preservation of reserve intestinal epithelial stem cells following severe ischemic injury

2019 ◽  
Vol 316 (4) ◽  
pp. G482-G494
Author(s):  
Liara M. Gonzalez ◽  
Amy Stieler Stewart ◽  
John Freund ◽  
Cecilia Renee Kucera ◽  
Christopher M. Dekaney ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ex Vivo ◽  
Recovery Period ◽  
Ischemic Injury ◽  
Stem Cell Population ◽  
Intestinal Epithelial ◽  
Epithelial Stem Cells ◽  
Ischemic Disease ◽  
Activated State

Intestinal ischemia is an abdominal emergency with a mortality rate >50%, leading to epithelial barrier loss and subsequent sepsis. Epithelial renewal and repair after injury depend on intestinal epithelial stem cells (ISC) that reside within the crypts of Lieberkühn. Two ISC populations critical to epithelial repair have been described: 1) active ISC (aISC; highly proliferative; leucine-rich-repeat-containing G protein-coupled receptor 5 positive, sex determining region Y-box 9 positive) and 2) reserve ISC [rISC; less proliferative; homeodomain only protein X (Hopx)+]. Yorkshire crossbred pigs (8–10 wk old) were subjected to 1–4 h of ischemia and 1 h of reperfusion or recovery by reversible mesenteric vascular occlusion. This study was designed to evaluate whether ISC-expressing biomarkers of aISCs or rISCs show differential resistance to ischemic injury and different contributions to the subsequent repair and regenerative responses. Our data demonstrate that, following 3–4 h ischemic injury, aISC undergo apoptosis, whereas rISC are preserved. Furthermore, these rISC are retained ex vivo in spheroids in which cell populations are enriched in the rISC biomarker Hopx. These cells appear to go on to provide a proliferative pool of cells during the recovery period. Taken together, these data indicate that Hopx+ cells are resistant to injury and are the likely source of epithelial renewal following prolonged ischemic injury. It is therefore possible that targeting reserve stem cells will lead to new therapies for patients with severe intestinal injury. NEW & NOTEWORTHY The population of reserve less-proliferative intestinal epithelial stem cells appears resistant to injury despite severe epithelial cell loss, including that of the active stem cell population, which results from prolonged mesenteric ischemia. These cells can change to an activated state and are likely indispensable to regenerative processes. Reserve stem cell targeted therapies may improve treatment and outcome of patients with ischemic disease.

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