scholarly journals Mensenchymal stem cells can delay radiation-induced crypt death: impact on intestinal CD44+ fragments

2015 ◽  
Vol 364 (2) ◽  
pp. 331-344 ◽  
Author(s):  
Peng-Yu Chang ◽  
Xing Jin ◽  
Yi-Yao Jiang ◽  
Li-Xian Wang ◽  
Yong-Jun Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Radiation Induced ◽  
Mensenchymal Stem Cells

scholarly journals Radiation-induced toxicity in rectal epithelial stem cell contributes to acute radiation injury in rectum

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Felipe Rodriguez Tirado ◽  
Payel Bhanja ◽  
Eduardo Castro-Nallar ◽  
Ximena Diaz Olea ◽  
Catalina Salamanca ◽  
...  
Keyword(s):  
Stem Cells ◽  
Ex Vivo ◽  
Cre Recombinase ◽  
Lineage Tracing ◽  
Common Side Effect ◽  
Rectal Injury ◽  
Male Mice ◽  
Pelvic Irradiation ◽  
Pelvic Malignancies ◽  
Radiation Induced

Abstract Background Radiation-induced rectal epithelial damage is a very common side effect of pelvic radiotherapy and often compromise the life quality and treatment outcome in patients with pelvic malignancies. Unlike small bowel and colon, effect of radiation in rectal stem cells has not been explored extensively. Here we demonstrate that Lgr5-positive rectal stem cells are radiosensitive and organoid-based transplantation of rectal stem cells mitigates radiation damage in rectum. Methods C57Bl6 male mice (JAX) at 24 h were exposed to pelvic irradiation (PIR) to determine the radiation effect in pelvic epithelium. Effect of PIR on Lgr5-positive rectal stem cells (RSCs) was determined in Lgr5-EGFP-Cre-ERT2 mice exposed to PIR. Effect of PIR or clinically relevant fractionated PIR on regenerative response of Lgr5-positive RSCs was examined by lineage tracing assay using Lgr5-eGFP-IRES-CreERT2; Rosa26-CAG-tdTomato mice with tamoxifen administration to activate Cre recombinase and thereby marking the ISC and their respective progeny. Ex vivo three-dimensional organoid cultures were developed from Lgr5-EGFP-Cre-ERT2 mice. Organoid growth was determined by quantifying the budding crypt/total crypt ratio. Organoids from Lgr5-EGFP-ires-CreERT2-TdT mice were transplanted in C57Bl6 male mice exposed to PIR. Engraftment and repopulation of Lgr5-positive RSCs were determined after tamoxifen administration to activate Cre recombinase in recipient mice. Statistical analysis was performed using Log-rank (Mantel-Cox) test and paired two-tail t test. Result Exposure to pelvic irradiation significantly damaged rectal epithelium with the loss of Lgr5+ve rectal stem cells. Radiosensitivity of rectal epithelium was also observed with exposure to clinically relevant fractionated pelvic irradiation. Regenerative capacity of Lgr5+ve rectal stem cells was compromised in response to fractionated pelvic irradiation. Ex vivo organoid study demonstrated that Lgr5+ve rectal stem cells are sensitive to both single and fractionated radiation. Organoid-based transplantation of Lgr5+ve rectal stem cells promotes repair and regeneration of rectal epithelium. Conclusion Lgr5-positive rectal stem cells are radiosensitive and contribute to radiation-induced rectal epithelial toxicity. Transplantation of Lgr5-positive rectal stem cells mitigates radiation-induced rectal injury and promotes repair and regeneration process in rectum.

scholarly journals Will mesenchymal stem cells be future directions for treating radiation-induced skin injury?

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhuoqun Fang ◽  
Penghong Chen ◽  
Shijie Tang ◽  
Aizhen Chen ◽  
Chaoyu Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Malignant Tumors ◽  
Skin Injury ◽  
Future Directions ◽  
Cytokines And Chemokines ◽  
Radiation Induced ◽  
The Common ◽  
Apoptotic Activity ◽  
Different Sources

AbstractRadiation-induced skin injury (RISI) is one of the common serious side effects of radiotherapy (RT) for patients with malignant tumors. Mesenchymal stem cells (MSCs) are applied to RISI repair in some clinical cases series except some traditional options. Though direct replacement of damaged cells may be achieved through differentiation capacity of MSCs, more recent data indicate that various cytokines and chemokines secreted by MSCs are involved in synergetic therapy of RISI by anti-inflammatory, immunomodulation, antioxidant, revascularization, and anti-apoptotic activity. In this paper, we not only discussed different sources of MSCs on the treatment of RISI both in preclinical studies and clinical trials, but also summarized the applications and mechanisms of MSCs in other related regenerative fields.

scholarly journals Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 42
Author(s):  
Xiaoyu Pu ◽  
Siyang Ma ◽  
Yan Gao ◽  
Tiankai Xu ◽  
Pengyu Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Radiation Damage ◽  
Therapeutic Potential ◽  
Damage Model ◽  
Bioactive Substances ◽  
Radiation Induced ◽  
Insight Into

Radiation-induced damage is a common occurrence in cancer patients who undergo radiotherapy. In this setting, radiation-induced damage can be refractory because the regeneration responses of injured tissues or organs are not well stimulated. Mesenchymal stem cells have become ideal candidates for managing radiation-induced damage. Moreover, accumulating evidence suggests that exosomes derived from mesenchymal stem cells have a similar effect on repairing tissue damage mainly because these exosomes carry various bioactive substances, such as miRNAs, proteins and lipids, which can affect immunomodulation, angiogenesis, and cell survival and proliferation. Although the mechanisms by which mesenchymal stem cell-derived exosomes repair radiation damage have not been fully elucidated, we intend to translate their biological features into a radiation damage model and aim to provide new insight into the management of radiation damage.

scholarly journals BlueBerry Isolate, Pterostilbene, Functions as a Potential Anticancer Stem Cell Agent in Suppressing Irradiation-Mediated Enrichment of Hepatoma Stem Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Chi-Ming Lee ◽  
Yen-Hao Su ◽  
Thanh-Tuan Huynh ◽  
Wei-Hwa Lee ◽  
Jeng-Fong Chiou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Tumor Cell Death ◽  
Invasion And Migration ◽  
Tumor Sphere ◽  
Flow Cytometric Method ◽  
Number Of Factors ◽  
Radiation Induced ◽  
And Migration ◽  
Sphere Formation

For many malignancies, radiation therapy remains the second option only to surgery in terms of its curative potential. However, radiation-induced tumor cell death is limited by a number of factors, including the adverse response of the tumor microenvironment to the treatment and either intrinsic or acquired mechanisms of evasive resistance, and the existence of cancer stem cells (CSCs). In this study, we demonstrated that using different doses of irradiation led to the enrichment of CD133+Mahlavu cells using flow cytometric method. Subsequently, CD133+Mahlavu cells enriched by irradiation were characterized for their stemness gene expression, self-renewal, migration/invasion abilities, and radiation resistance. Having established irradiation-enriched CD133+Mahlavu cells with CSC properties, we evaluated a phytochemical, pterostilbene (PT), found abundantly in blueberries, against irradiation-enriched CSCs. It was shown that PT treatment dose-dependently reduced the enrichment of CD133+Mahlavu cells upon irradiation; PT treatment also prevented tumor sphere formation, reduced stemness gene expression, and suppressed invasion and migration abilities as well as increasing apoptosis of CD133+Mahlavu CSCs. Based on our experimental data, pterostilbene could be used to prevent the enrichment of CD133+hepatoma CSCs and should be considered for future clinical testing as a combined agent for HCC patients.

scholarly journals The evolving definition of salivary gland stem cells

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Cecilia Rocchi ◽  
Lara Barazzuol ◽  
Rob P. Coppes
Keyword(s):  
Stem Cells ◽  
Salivary Gland ◽  
Adult Stem Cell ◽  
Cell Types ◽  
Research Field ◽  
New Therapeutic Approaches ◽  
Recent Developments ◽  
Radiation Induced ◽  
Definition Of

AbstractDysfunction of the salivary gland and irreversible hyposalivation are the main side effects of radiotherapy treatment for head and neck cancer leading to a drastic decrease of the quality of life of the patients. Approaches aimed at regenerating damaged salivary glands have been proposed as means to provide long-term restoration of tissue function in the affected patients. In studies to elucidate salivary gland regenerative mechanisms, more and more evidence suggests that salivary gland stem/progenitor cell behavior, like many other adult tissues, does not follow that of the hard-wired professional stem cells of the hematopoietic system. In this review, we provide evidence showing that several cell types within the salivary gland epithelium can serve as stem/progenitor-like cells. While these cell populations seem to function mostly as lineage-restricted progenitors during homeostasis, we indicate that upon damage specific plasticity mechanisms might be activated to take part in regeneration of the tissue. In light of these insights, we provide an overview of how recent developments in the adult stem cell research field are changing our thinking of the definition of salivary gland stem cells and their potential plasticity upon damage. These new perspectives may have important implications on the development of new therapeutic approaches to rescue radiation-induced hyposalivation.

scholarly journals Mechanism of Action of Diallyl Sulphide in Ameliorating the Hematopoietic Radiation Injury

2021 ◽  
Author(s):  
Omika Katoch ◽  
Mrinalini Tiwari ◽  
Namita Kalra ◽  
Paban K. Agrawala
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Radiation Induced ◽  
Medicinal Properties ◽  
Marrow Cellularity

AbstractDiallyl sulphide (DAS), the pungent component of garlic, is known to have several medicinal properties and has recently been shown to have radiomitigative properties. The present study was performed to better understand its mode of action in rendering radiomitigation. Evaluation of the colonogenic ability of hematopoietic progenitor cells (HPCs) on methocult media, proliferation and differentiation of hematopoietic stem cells (HSCs), and transplantation of stem cells were performed. The supporting tissue of HSCs was also evaluated by examining the histology of bone marrow and in vitro colony-forming unit–fibroblast (CFU-F) count. Alterations in the levels of IL-5, IL-6 and COX-2 were studied as a function of radiation or DAS treatment. It was observed that an increase in proliferation and differentiation of hematopoietic stem and progenitor cells occurred by postirradiation DAS administration. It also resulted in increased circulating and bone marrow homing of transplanted stem cells. Enhancement in bone marrow cellularity, CFU-F count, and cytokine IL-5 level were also evident. All those actions of DAS that could possibly add to its radiomitigative potential and can be attributed to its HDAC inhibitory properties, as was observed by the reversal radiation induced increase in histone acetylation.

Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model

2021 ◽  
Author(s):  
Wei Hu ◽  
Jiawu Liang ◽  
Song Liao ◽  
Zhidong Zhao ◽  
Yuxing Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Flow Cytometry ◽  
Genomic Stability ◽  
Bone Defects ◽  
Self Renewal ◽  
Tnf Α ◽  
Radiation Induced ◽  
Γ Ray

Abstract Background Ionizing radiation poses a challenge to the healing of bone defects. Radiation therapy and accidental exposure to gamma-ray (γ-ray) radiation inhibit bone formation and increase the risk of fractures. Cortical bone-derived stem cells (CBSCs) are essential for osteogenic lineages, bone maintenance, and repair. This study aimed to investigate the effects of melatonin on postradiation CBSCs and bone defects. Methods CBSCs were extracted from C57/BL6 mice and were identified by flow cytometry. The effects of exogenous melatonin on the self-renewal and osteogenic capacity of postradiation CBSCs were detected in vitro. The underlying mechanisms in terms of genomic stability, apoptosis and oxidative stress-related signaling were further analyzed by western blotting, flow cytometry and immunofluorescence. Finally, the effects of melatonin on healing in postradiation bone defects were evaluated in vivo by micro-CT and immunohistochemical analysis. Results The radiation-induced reduced self-renewal and osteogenic capacity were partially reversed in postradiation CBSCs treated with melatonin. Melatonin maintained the genomic stability and apoptosis of postradiation CBSCs, and intracellular oxidative stress was decreased significantly while antioxidant-related enzymes were enhanced. Western blotting verified the anti-inflammatory effect of melatonin by downregulating the levels of IL-6 and TNF-α via extracellular regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase 1 (HO-1) signaling, distinct from its antioxidant effect via NRF2 signaling. In vivo experiments demonstrated that the newly formed bone in the melatonin plus Matrigel group had higher trabecular bone volume per tissue volume (BV/TV) and bone mineral density (BMD) values, and lower levels of IL-6 and TNF-α than those in the irradiation and the Matrigel groups. Conclusions This study suggested the potential of melatonin to protect CBSCs against γ-ray radiation and to assist the healing of postradiation bone defects.

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