Strategies of epithelial repair: modulation of stem cell and transit amplifying cell proliferation

1998 ◽  
Vol 111 (19) ◽  
pp. 2867-2875 ◽  
Author(s):  
M.S. Lehrer ◽  
T.T. Sun ◽  
R.M. Lavker
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Dna Synthesis ◽  
Cell Replication ◽  
Epithelial Stem Cells ◽  
Cell Cycle Time ◽  
Double Labeling ◽  
Corneal Epithelial ◽  
Epithelial Repair

Using double labeling techniques, we studied the replication of corneal epithelial stem cells that reside exclusively in the limbal zone, and their progeny transit amplifying cells. We show that corneal epithelial stem cells can be induced to enter DNA synthesis by wounding and by TPA. We demonstrate the existence of a hierarchy of TA cells; those of peripheral cornea undergo at least two rounds of DNA synthesis before they become post-mitotic, whereas those of central cornea are capable of only one round of division. However, the cell cycle time of these TA cells can be shortened and the number of times these TA cells can replicate is increased in response to wounding. These results thus demonstrate three strategies of epithelial repair: (i) stem cell replication, (ii) the unleashing of additional rounds of cell proliferation that remain as an untapped reserve under normal circumstances, and (iii) enhancement of TA cell proliferation via a shortening of the cycling time.

scholarly journals Stem Cells in the Path of Light, from Corneal to Retinal Reconstruction

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 873
Author(s):  
Ovidiu Samoila ◽  
Lacramioara Samoila
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Clinical Success ◽  
Corneal Stroma ◽  
Cell Transplant ◽  
Inclusion Criteria ◽  
Epithelial Stem Cells ◽  
Corneal Epithelial ◽  
Stem Cells Transplantation ◽  
Limbal Epithelial Stem Cells

The future of eye reconstruction invariably includes stem cells transplantation. Corneal limbus, corneal stroma, trabeculum, retinal cells, optic nerve, and all structures that are irreversibly damaged and have no means to be repaired or replaced, through conventional treatment or surgery, represent targets for stem cell reconstruction. This review tries to answer the question if there is any clinical validation for stem therapies, so far, starting from the cornea and, on the path of light, arriving to the retina. The investigation covers the last 10 years of publications. From 2385 published sources, we found 56 clinical studies matching inclusion criteria, 39 involving cornea, and 17 involving retina. So far, corneal epithelial reconstruction seems well validated clinically. Enough clinical data are collected to allow some form of standardization for the stem cell transplant procedures. Cultivated limbal epithelial stem cells (CLET), simple limbal epithelial transplant (SLET), and oral mucosa transplantation are implemented worldwide. In comparison, far less patients are investigated in retinal stem reconstructions, with lower anatomical and clinical success, so far. Intravitreal, subretinal, and suprachoroidal approach for retinal stem therapies face specific challenges.

Delayed Loss of Corneal Epithelial Stem Cells in a Chemical Injury Model Associated with Limbal Stem Cell Deficiency in Rabbits

2011 ◽  
Vol 36 (12) ◽  
pp. 1098-1107 ◽  
Author(s):  
Tamar Kadar ◽  
Vered Horwitz ◽  
Rita Sahar ◽  
Maayan Cohen ◽  
Liat Cohen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Limbal Stem Cell Deficiency ◽  
Epithelial Stem Cells ◽  
Corneal Epithelial ◽  
Chemical Injury ◽  
Injury Model ◽  
Limbal Stem Cell

scholarly journals A direct effect of the autonomic nervous system on somatic stem cell proliferation?

2019 ◽  
Vol 316 (1) ◽  
pp. R1-R5
Author(s):  
Elizabeth A. Davis ◽  
Megan J. Dailey
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Nervous System ◽  
Stem Cell ◽  
Autonomic Nervous System ◽  
Somatic Stem Cell ◽  
Epithelial Stem Cells ◽  
Somatic Stem Cells ◽  
Stem Cell Proliferation ◽  
Autonomic Nervous

Regulation of somatic stem cell proliferation is critical for the maintenance of tissue and organ function throughout the body. Modulators of this process include nutrients and peptides, but the role of an autonomic neural influence on stem cell proliferation has been neglected. This article describes the literature in support of autonomic nervous system (ANS) influence on somatic stem cells, with emphasis on intestinal epithelial stem cells (IESCs) as a representative somatic stem cell. Based on the current available data, models for the direct influence of both branches of the ANS (the sympathetic and parasympathetic nervous systems) on IESCs are outlined. Finally, the prospect of treatments derived from ANS influence on somatic stem cells is explored.

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 Mitochondria regulate intestinal stem cell proliferation and epithelial homeostasis through FOXO

2020 ◽  
Vol 31 (14) ◽  
pp. 1538-1549
Author(s):  
Fan Zhang ◽  
Mehdi Pirooznia ◽  
Hong Xu
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Stem Cell ◽  
Electron Transport Chain ◽  
Intestinal Stem Cell ◽  
Stem Cell Proliferation ◽  
Epithelial Homeostasis ◽  
Chain Complexes ◽  
Transport Chain

Deficiencies in electron transport chain complexes increase the activity of FOXO transcription factor in Drosophila midgut stem cells, which impairs stem cell proliferation and enterocyte specification.

scholarly journals Derivation and Characterization of EGFP-Labeled Rabbit Limbal Mesenchymal Stem Cells and Their Potential for Research in Regenerative Ophthalmology

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1134
Author(s):  
Julia I. Khorolskaya ◽  
Daria A. Perepletchikova ◽  
Daniel V. Kachkin ◽  
Kirill E. Zhurenkov ◽  
Elga I. Alexander-Sinkler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Fluorescent Protein ◽  
Rabbit Model ◽  
Stem Cell Markers ◽  
Epithelial Stem Cells ◽  
Limbal Stem Cell ◽  
Green Fluorescent

The development of cell-based approaches to the treatment of various cornea pathologies, including limbal stem cell deficiency (LSCD), is an area of current interest in regenerative biomedicine. In this context, the shortage of donor material is urgent, and limbal mesenchymal stem cells (L-MSCs) may become a promising cell source for the development of these novel approaches, being established mainly within the rabbit model. In this study, we obtained and characterized rabbit L-MSCs and modified them with lentiviral transduction to express the green fluorescent protein EGFP (L-MSCs-EGFP). L-MSCs and L-MSCs-EGFP express not only stem cell markers specific for mesenchymal stem cells but also ABCG2, ABCB5, ALDH3A1, PAX6, and p63a specific for limbal epithelial stem cells (LESCs), as well as various cytokeratins (3/12, 15, 19). L-MSCs-EGFP have been proven to differentiate into adipogenic, osteogenic, and chondrogenic directions, as well as to transdifferentiate into epithelial cells. The possibility of using L-MSCs-EGFP to study the biocompatibility of various scaffolds developed to treat corneal pathologies was demonstrated. L-MSCs-EGFP may become a useful tool for studying regenerative processes occurring during the treatment of various corneal pathologies, including LSCD, with the use of cell-based technologies.

scholarly journals Unveiling role of Sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer

2020 ◽  
Author(s):  
Luciana Petti ◽  
Giulia Rizzo ◽  
Federica Rubbino ◽  
Sudharshan Elangovan ◽  
Piergiuseppe Colombo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Normal Mucosa ◽  
Genetically Engineered ◽  
Colorectal Carcinogenesis ◽  
Intestinal Stem Cells ◽  
Cancer Information ◽  
Intestinal Epithelial ◽  
Epithelial Stem Cells ◽  
Mucosal Regeneration

Abstract BackgroundSphingosine-1-phosphate receptor 2 (S1PR2) mediates pleiotropic functions encompassing cell proliferation, survival, and migration, which become collectively de-regulated in cancer. Information onto whether S1PR2 participates in colorectal carcinogenesis/cancer is scanty, and we set out to fill the gap.MethodsWe screened expression changes of S1PR2 in human CRC and matched normal mucosa specimens [N = 76]. We compared CRC arising in inflammation-driven and genetically engineered models in wild-type (S1PR2+/+) and S1PR2 deficient (S1PR2−/−) mice. We reconstituted S1PR2 expression in RKO cells and assessed their growth in xenografts. Functionally, we mimicked ablation of S1PR2 in normal mucosa by treating S1PR2+/+ organoids with JTE013, and characterized intestinal epithelial stem cells isolated from S1PR2−/−Lgr5-EGFP- mice.ResultsS1PR2 expression was lost in 33% of CRC; in 55%, it was significantly decreased, only 12% retaining expression comparable to normal mucosa. Both colitis-induced and genetic Apc+/min mouse models of CRC showed a higher incidence in size and number of carcinomas and/or high-grade adenomas, with increased cell proliferation in S1PR2−/− mice compared to S1PR2+/+ controls. Loss of S1PR2 impaired mucosal regeneration, ultimately promoting the expansion of intestinal stem cells. Whereas its overexpression attenuated cell cycle progression, it reduced the phosphorylation of AKT and augmented the levels of PTEN.ConclusionsIn normal colonic crypts, S1PR2 gains expression along with intestinal epithelial cells differentiation, but not in intestinal stem cells, and contrasts intestinal tumorigenesis by promoting epithelial differentiation, preventing the expansion of stem cells and braking their malignant transformation. Targeting of S1PR2 may be of therapeutic benefit for CRC expressing high Lgr5.

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