scholarly journals Nonmicrobial Activation of TLRs Controls Intestinal Growth, Wound Repair, and Radioprotection

2021 ◽  
Vol 11 ◽  
Author(s):  
William F. Stenson ◽  
Matthew A. Ciorba
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hyaluronic Acid ◽  
Wound Repair ◽  
Epithelial Proliferation ◽  
Epithelial Stem Cells ◽  
Radiation Induced ◽  
Induced Apoptosis ◽  
A Site ◽  
Hyaluronic Acid Binding

TLRs, key components of the innate immune system, recognize microbial molecules. However, TLRs also recognize some nonmicrobial molecules. In particular, TLR2 and TLR4 recognize hyaluronic acid, a glycosaminoglycan in the extracellular matrix. In neonatal mice endogenous hyaluronic acid binding to TLR4 drives normal intestinal growth. Hyaluronic acid binding to TLR4 in pericryptal macrophages results in cyclooxygenase2- dependent PGE2 production, which transactivates EGFR in LGR5+ crypt epithelial stem cells leading to increased proliferation. The expanded population of LGR5+ stem cells leads to crypt fission and lengthening of the intestine and colon. Blocking this pathway at any point (TLR4 activation, PGE2 production, EGFR transactivation) results in diminished intestinal and colonic growth. A similar pathway leads to epithelial proliferation in wound repair. The repair phase of dextran sodium sulfate colitis is marked by increased epithelial proliferation. In this model, TLR2 and TLR4 in pericryptal macrophages are activated by microbial products or by host hyaluronic acid, resulting in production of CXCL12, a chemokine. CXCL12 induces the migration of cyclooxygenase2-expressing mesenchymal stem cells from the lamina propria of the upper colonic crypts to a site adjacent to LGR5+ epithelial stem cells. PGE2 released by these mesenchymal stem cells transactivates EGFR in LGR5+ epithelial stem cells leading to increased proliferation. Several TLR2 and TLR4 agonists, including hyaluronic acid, are radioprotective in the intestine through the inhibition of radiation-induced apoptosis in LGR5+ epithelial stem cells. Administration of exogenous TLR2 or TLR4 agonists activates TLR2/TLR4 on pericryptal macrophages inducing CXCL12 production with migration of cyclooxygenase2-expressing mesenchymal stem cells from the lamina propria of the villi to a site adjacent to LGR5+ epithelial stem cells. PGE2 produced by these mesenchymal stem cells, blocks radiation-induced apoptosis in LGR5+ epithelial stem cells by an EGFR mediated pathway.

scholarly journals Hyaluronic acid is radioprotective in the intestine through a TLR4 and COX-2-mediated mechanism

2012 ◽  
Vol 302 (3) ◽  
pp. G309-G316 ◽  
Author(s):  
Terrence E. Riehl ◽  
Lynne Foster ◽  
William F. Stenson
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Radiation Therapy ◽  
Hyaluronic Acid ◽  
Intestinal Epithelium ◽  
Fold Increase ◽  
Radiation Induced ◽  
Cox 2 ◽  
Total Body ◽  
Induced Apoptosis

The intestinal epithelium is sensitive to radiation injury. Damage to the intestinal epithelium is dose limiting in radiation therapy of abdominal cancers. There is a need for agents that can be given before radiation therapy to protect the intestinal epithelium. C57BL6 mice were subjected to 12 Gy of total body radiation. Some mice received intraperitoneal hyaluronic acid (HA) before radiation. Mice were killed 6 h after radiation to assess radiation-induced apoptosis in the intestine; other mice were killed at 84 h to assess crypt survival. Total body radiation (12 Gy) resulted in increased expression of HA synthases and HA in the intestine and increased plasma HA (5-fold). Intraperitoneal injection of HA (30 mg/kg) before radiation resulted in a 1.8-fold increase in intestinal crypt survival and a decrease in radiation-induced apoptosis. The radioprotective effects of HA were not seen in Toll-like receptor 4 (TLR4)- or cyclooxygenase-2 (COX-2)-deficient mice. Intraperitoneal injection of HA induced a 1.5-fold increase in intestinal COX-2 expression, a 1.5-fold increase in intestinal PGE2, and the migration of COX-2-expressing mesenchymal stem cells from the lamina propria in the villi to the lamina propria near the crypt. We conclude that 1) radiation induces increased HA expression through inducing HA synthases, 2) intraperitoneal HA given before radiation reduces radiation-induced apoptosis and increases crypt survival, and 3) these radioprotective effects are mediated through TLR4, COX-2, and the migration of COX-2-expressing mesenchymal stem cells.

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.

Effect of electrical stimulation on chondrogenic differentiation of mesenchymal stem cells cultured in hyaluronic acid – Gelatin injectable hydrogels

2020 ◽  
Vol 134 ◽  
pp. 107536 ◽  
Author(s):  
Juan Jairo Vaca-González ◽  
Sandra Clara-Trujillo ◽  
María Guillot-Ferriols ◽  
Joaquín Ródenas-Rochina ◽  
María J. Sanchis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Electrical Stimulation ◽  
Hyaluronic Acid ◽  
Chondrogenic Differentiation ◽  
Injectable Hydrogels ◽  
Cells Cultured

scholarly journals Adenosine Triphosphate Prevents Serum Deprivation-Induced Apoptosis in Human Mesenchymal Stem Cells via Activation of the MAPK Signaling Pathways

Stem Cells ◽  
2014 ◽  
Vol 33 (1) ◽  
pp. 211-218 ◽  
Author(s):  
Jessica L. Berlier ◽  
Sabrina Rigutto ◽  
Antoine Dalla Valle ◽  
Jessica Lechanteur ◽  
Muhammad S. Soyfoo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Adenosine Triphosphate ◽  
Human Mesenchymal Stem Cells ◽  
Mapk Signaling ◽  
Serum Deprivation ◽  
Induced Apoptosis ◽  
Mapk Signaling Pathways

Exosomal MicroRNA-204 Derived from Bone Marrow Mesenchymal Stem Cells (BMSCs) Inhibits Cell Proliferation and Induces Apoptosis Through NF-κB Signaling Pathway in Breast Cancer

2022 ◽  
Vol 12 (2) ◽  
pp. 273-278
Author(s):  
Daqing Jiang ◽  
Xianxin Xie ◽  
Cong Wang ◽  
Weijie Li ◽  
Jianjun He
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Marrow Mesenchymal Stem Cells ◽  
Induced Apoptosis ◽  
Signaling Activation

Our study intends to assess the relationship between exosomes derived from bone marrow mesenchymal stem cells (BMSC-exo) and breast cancer. BMSC-exo were isolated and characterized by transmission electron microscopy. After transfection of BMSCs with miR-204 inhibitor, breast cancer cells were incubated with BMSC-exo followed by analysis of cell proliferation by CCK-8 assay, cell apoptosis by flow cytometry, and expression of apoptosis-related protein and NF-κB signaling by western blot. The co-culture of BMSC-exo with breast cancer cells enhanced miR-204 transcription, inhibited cell proliferation and induced apoptosis. Further, BMSC-exo accelerated apoptosis as demonstrated by the increased level of Bax and casepase-3 and decreased Bcl-2 expression, as well as reduced NF-κB signaling activity. But knockdown of miR-204 abolished the effect of BMSC-exo on apoptosis and proliferation with NF-κB signaling activation. In conclusion, miR-204 from BMSC-exo restrains growth of breast cancer cell and might be a novel target for treating breast cancer.

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