Intestinal stem cells and stem cell-based therapy for intestinal diseases

Abstract Intestinal stem cells, which are capable of both self-renewal and differentiation to mature cell types, are responsible for maintaining intestinal epithelial homeostasis. Recent evidence indicates that these processes are mediated, in part, through nutritional status in response to diet. Diverse dietary patterns including caloric restriction, fasting, high-fat diets, ketogenic diets and high-carbohydrate diets as well as other nutrients control intestinal stem cell self-renewal and differentiation through nutrient-sensing pathways such as mTOR and AMPK. Herein, we summarize the current understanding of how intestinal stem cells contribute to intestinal epithelial homeostasis and diseases. We also discuss the effects of diet and nutrient-sensing pathways on intestinal stem cell self-renewal and differentiation, as well as their potential application in the prevention and treatment of intestinal diseases.

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Preclinical efficacy of stem cell therapy for skin flap: a systematic review and meta-analysis

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02103-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yuan Li ◽

Qi-lin Jiang ◽

Leanne Van der Merwe ◽

Dong-hao Lou ◽

Cai Lin

Keyword(s):

Systematic Review ◽

Stem Cells ◽

Stem Cell ◽

Survival Rate ◽

Meta Analysis ◽

Skin Flap ◽

Cochrane Library ◽

Skin Flaps ◽

Cell Based Therapy ◽

Stem Cell Treatment

Abstract Background A skin flap is one of the most critical surgical techniques for the restoration of cutaneous defects. However, the distal necrosis of the skin flap severely restricts the clinical application of flap surgery. As there is no consensus on the treatment methods to prevent distal necrosis of skin flaps, more effective and feasible interventions to prevent skin flaps from necrosis are urgently needed. Stem therapy as a potential method to improve the survival rate of skin flaps is receiving increasing attention. Methods This review followed the recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statements. Twenty studies with 500 animals were included by searching Web of Science, EMBASE, PubMed, and Cochrane Library databases, up until October 8, 2020. Moreover, the references of the included articles were searched manually to obtain other studies. All analyses were conducted using Review Manager V.5.3 software. Results Meta-analysis of all 20 studies demonstrated stem cell treatment has significant effects on reducing necrosis of skin flap compared with the control group (SMD: 3.20, 95% CI 2.47 to 3.93). Besides, subgroup analysis showed differences in the efficacy of stem cells in improving the survival rate of skin flaps in areas of skin flap, cell type, transplant types, and method of administration of stem cells. The meta-analysis also showed that stem cell treatment had a significant effect on increasing blood vessel density (SMD: 2.96, 95% CI 2.21 to 3.72) and increasing the expression of vascular endothelial growth factor (VEGF, SMD: 4.34, 95% CI 2.48 to 6.1). Conclusions The preclinical evidence of our systematic review indicate that stem cell-based therapy is effective for promoting early angiogenesis by up regulating VEGF and ultimately improving the survival rate of skin flap. In summary, small area skin flap, the administration method of intra-arterial injection, ASCs and MSCs, and xenogenic stem cells from humans showed more effective for the survival of animal skin flaps. In general, stem cell-based therapy may be a promising method to prevent skin flap necrosis.

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

Surgical Technology Online ◽

10.52198/21.sti.38.hr1387 ◽

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.

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Immunostaining of Lgr5, an Intestinal Stem Cell Marker, in Normal and Premalignant Human Gastrointestinal Tissue

The Scientific World JOURNAL ◽

10.1100/tsw.2008.148 ◽

2008 ◽

Vol 8 ◽

pp. 1168-1176 ◽

Cited By ~ 76

Author(s):

Laren Becker ◽

Qin Huang ◽

Hiroshi Mashimo

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Stem Cell Niche ◽

Intestinal Stem Cells ◽

Stem Cell Marker ◽

Tumor Initiating Cells ◽

Colonic Adenomas ◽

Potential Marker ◽

Cell Niche ◽

Crypt Base

Lgr5 has recently been identified as a murine marker of intestinal stem cells. Its expression has not been well characterized in human gastrointestinal tissues, but has been reported in certain cancers. With the increasing appreciation for the role of cancer stem cells or tumor-initiating cells in certain tumors, we sought to explore the expression of Lgr5 in normal and premalignant human gastrointestinal tissues. Using standard immunostaining, we compared expression of Lgr5 in normal colon and small intestine vs. small intestinal and colonic adenomas and Barrett's esophagus. In the normal tissue, Lgr5 was expressed in the expected stem cell niche, at the base of crypts, as seen in mice. However, in premalignant lesions, Lgr5+cells were not restricted to the crypt base. Additionally, their overall numbers were increased. In colonic adenomas, Lgr5+cells were commonly found clustered at the luminal surface and rarely at the crypt base. Finally, we compared immunostaining of Lgr5 with that of CD133, a previously characterized marker for tumor-initiating cells in colon cancer, and found that they identified distinct subpopulations of cells that were in close proximity, but did not costain. Our findings suggest that (1) Lgr5 is a potential marker of intestinal stem cells in humans and (2) loss of restriction to the stem cell niche is an early event in the premalignant transformation of stem cells and may play a role in carcinogenesis.

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Stem cells in brain diseases: From cell replacement to disease modeling

Translational Neuroscience ◽

10.2478/s13380-011-0017-2 ◽

2011 ◽

Vol 2 (2) ◽

Author(s):

Nina Kosi ◽

Dinko Mitrečić

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Disease Modeling ◽

Neurological Diseases ◽

Rapid Development ◽

Modern Society ◽

Brain Diseases ◽

Stem Cell Technology ◽

Cell Based Therapy

AbstractNeurological diseases are recognized as one of the most significant burdens of the modern society. Therefore, a new therapeutic approach applicable to nervous system represents priority of today’s medicine. A rapid development of stem cell technology in the last two decades introduced a possibility to regenerate disease-affected nervous tissue. In this vein, stem cells are envisioned as a replacement for lost neurons, a source of trophic support, a therapeutic vehicle, and as a tool for in vitro modeling. This article reviews the current concepts in stem cell-based therapy of neurological diseases and comments ongoing efforts aiming at clinical translation.

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Label-Free Rapid Separation and Enrichment of Bone Marrow-Derived Mesenchymal Stem Cells from a Heterogeneous Cell Mixture Using a Dielectrophoresis Device

Sensors ◽

10.3390/s18093007 ◽

2018 ◽

Vol 18 (9) ◽

pp. 3007 ◽

Cited By ~ 5

Author(s):

Junya Yoshioka ◽

Yu Ohsugi ◽

Toru Yoshitomi ◽

Tomoyuki Yasukawa ◽

Naoki Sasaki ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Gradient Method ◽

Label Free ◽

Rapid Separation ◽

Isolation System ◽

Tissue Samples ◽

Cell Based Therapy

Bone marrow-derived mesenchymal stem cells (BMSCs) are an important cell resource for stem cell-based therapy, which are generally isolated and enriched by the density-gradient method based on cell size and density after collection of tissue samples. Since this method has limitations with regards to purity and repeatability, development of alternative label-free methods for BMSC separation is desired. In the present study, rapid label-free separation and enrichment of BMSCs from a heterogeneous cell mixture with bone marrow-derived promyelocytes was successfully achieved using a dielectrophoresis (DEP) device comprising saw-shaped electrodes. Upon application of an electric field, HL-60 cells as models of promyelocytes aggregated and floated between the saw-shaped electrodes, while UE7T-13 cells as models of BMSCs were effectively captured on the tips of the saw-shaped electrodes. After washing out the HL-60 cells from the device selectively, the purity of the UE7T-13 cells was increased from 33% to 83.5% within 5 min. Although further experiments and optimization are required, these results show the potential of the DEP device as a label-free rapid cell isolation system yielding high purity for rare and precious cells such as BMSCs.

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Study on the Therapeutic Mechanism of LXGYD on Intestinal Stem Cells and Tight Junction Proteins in GI-ARS Rats

10.21203/rs.3.rs-1112710/v1 ◽

2021 ◽

Author(s):

Ziqiao Yan ◽

Bofeng Yin ◽

Yuguo Wang ◽

Jian Feng ◽

Qianyu Yang ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Health Status ◽

Tight Junction ◽

Western Blotting ◽

Rat Model ◽

Protective Efficacy ◽

Intestinal Stem Cells ◽

Pathological Analysis ◽

Chinese Herbal

Abstract Background: Gastrointestinal acute radiation injury syndrome (GI-ARS) is potentially lethal and may occur after exposure to high radiation doses. Various chemical and biological agents have been developed to treat GI-ARS. However, their clinical utility is limited as they induce serious adverse reactions at their effective doses. Chinese herbal medicines have attracted attention because of their protective efficacy and low toxicity in radiation exposure treatment. However, their cellular and molecular mechanisms remain unknown. Here, we investigated the effects of the Chinese herbal Liangxue-Guyuan-Yishen decoction (LXGYD) on the intestinal stem cells and signal pathways of a GI-ARS rat model. Currently, there are limited treatment methods available globally; LXGYD might be a potential therapeutic option for patients with GI-ARS. Methods: The rat GI-ARS model was prepared by whole-body irradiation with 10-Gy of 60Co-γ rays. Various LXGYD concentrations were intragastrically administered to the irradiated rats. Health status and survival of the rats were evaluated and the protective efficacy of LXGYD on the intestines was assayed by pathological analysis. The active principles in LXGYD were detected by liquid chromatography-mass spectrometry (LC-MS) and their potential targets and pathways were screened by network pharmacological analysis. Intestinal stem cell proliferation, intestinal epithelial tight junction (TJ) protein expression, and regulatory pathways were explored by immunohistochemistry (IHC), western blotting (WB), and real-time quantitative polymerase chain reaction (RT-qPCR), respectively.Results: LXGYD administration significantly improved health status and survival in GI-ARS rats. The pathological analysis showed that LXGYD ameliorated radiation-induced intestinal injury. The LXGYD infusion significantly promoted LGR5+ stem cell regeneration in the ileal crypts, upregulated TJ proteins, and accelerated crypt reconstruction in the irradiated rats in a dose-dependent manner. LC-MS revealed ≥ 13 LXGYD constituents that might contribute to its protective effects. Involvement of the WNT and MEK/ERK pathways in intestinal repair and recovery were screened by network pharmacology analysis and validated by western blotting.Conclusions: The present study disclosed a heretofore unrecognized role of the Chinese herbal LXGYD in rescuing the intestinal stem cells of a GI-ARS rat model. It also showed that the WNT and MEK/ERK pathways may be involved in LXGYD-mediated intestinal regeneration in GI-ARS.

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Stem cell-based therapy for Parkinson’s disease with a focus on human endometrium-derived mesenchymal stem cells

Journal of Cellular Physiology ◽

10.1002/jcp.27182 ◽

2018 ◽

Vol 234 (2) ◽

pp. 1326-1335 ◽

Cited By ~ 12

Author(s):

Saeid Bagheri-Mohammadi ◽

Mohammad Karimian ◽

Behrang Alani ◽

Javad Verdi ◽

Rana Moradian Tehrani ◽

...

Keyword(s):

Parkinson’S Disease ◽

Stem Cells ◽

Parkinson's Disease ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Human Endometrium ◽

Cell Based Therapy

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Glutathione–Allylsulfur Conjugates as Mesenchymal Stem Cells Stimulating Agents for Potential Applications in Tissue Repair

International Journal of Molecular Sciences ◽

10.3390/ijms21051638 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1638 ◽

Cited By ~ 1

Author(s):

Emilia Di Giovanni ◽

Silvia Buonvino ◽

Ivano Amelio ◽

Sonia Melino

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Tissue Repair ◽

Dermal Fibroblasts ◽

Water Soluble ◽

Dependent Manner ◽

Tissue Repair And Regeneration ◽

Stem Cell Delivery ◽

Cell Based Therapy

The endogenous gasotransmitter H2S plays an important role in the central nervous, respiratory and cardiovascular systems. Accordingly, slow-releasing H2S donors are powerful tools for basic studies and innovative pharmaco-therapeutic agents for cardiovascular and neurodegenerative diseases. Nonetheless, the effects of H2S-releasing agents on the growth of stem cells have not been fully investigated. H2S preconditioning can enhance mesenchymal stem cell survival after post-ischaemic myocardial implantation; therefore, stem cell therapy combined with H2S may be relevant in cell-based therapy for regenerative medicine. Here, we studied the effects of slow-releasing H2S agents on the cell growth and differentiation of cardiac Lin− Sca1+ human mesenchymal stem cells (cMSC) and on normal human dermal fibroblasts (NHDF). In particular, we investigated the effects of water-soluble GSH–garlic conjugates (GSGa) on cMSC compared to other H2S-releasing agents, such as Na2S and GYY4137. GSGa treatment of cMSC and NHDF increased their cell proliferation and migration in a concentration dependent manner with respect to the control. GSGa treatment promoted an upregulation of the expression of proteins involved in oxidative stress protection, cell–cell adhesion and commitment to differentiation. These results highlight the effects of H2S-natural donors as biochemical factors that promote MSC homing, increasing their safety profile and efficacy after transplantation, and the value of these donors in developing functional 3D-stem cell delivery systems for cardiac muscle tissue repair and regeneration.

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Recent Overview of the Use of iPSCs Huntington’s Disease Modeling and Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms21062239 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2239 ◽

Cited By ~ 6

Author(s):

Maria Csobonyeiova ◽

Stefan Polak ◽

Lubos Danisovic

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Disease Modeling ◽

Cell Types ◽

Cag Repeats ◽

Neural Cells ◽

Behavioral Impairment ◽

Cell Based Therapy

Huntington’s disease (HD) is an inherited, autosomal dominant, degenerative disease characterized by involuntary movements, cognitive decline, and behavioral impairment ending in death. HD is caused by an expansion in the number of CAG repeats in the huntingtin gene on chromosome 4. To date, no effective therapy for preventing the onset or progression of the disease has been found, and many symptoms do not respond to pharmacologic treatment. However, recent results of pre-clinical trials suggest a beneficial effect of stem-cell-based therapy. Induced pluripotent stem cells (iPSCs) represent an unlimited cell source and are the most suitable among the various types of autologous stem cells due to their patient specificity and ability to differentiate into a variety of cell types both in vitro and in vivo. Furthermore, the cultivation of iPSC-derived neural cells offers the possibility of studying the etiopathology of neurodegenerative diseases, such as HD. Moreover, differentiated neural cells can organize into three-dimensional (3D) organoids, mimicking the complex architecture of the brain. In this article, we present a comprehensive review of recent HD models, the methods for differentiating HD–iPSCs into the desired neural cell types, and the progress in gene editing techniques leading toward stem-cell-based therapy.

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