Effects of Mesenchymal Stem Cells Treatment on Radiation-Induced Proctitis in Rats
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Purpose: There are no effective treatment methods with which to control complications of radiation proctitis with fistula or re current bleeding following radiation treatment for prostate, cervical, or rectal cancer. Mesenchymal stem cells (MSCs) can induce immune modification, resulting in tissue repair and regeneration. Therefore, we used a rat model of radiation-induced proctitis and observed the effects of using human placenta-derived (PD) and adipose tissue-derived (AD) MSCs. Materials and Methods: Female Sprague Dawley rats were irradiated at the pelvic area with 25 Gy. We injected 1×106 cells of hu man PD-MSCs, human AD-MSCs, human foreskin fibroblasts, and control media into the rectal submucosa following irradia tion. We sacrificed rats for pathologic evaluation. Results: Fibrosis on the rectum was reduced in both MSC groups, compared to the control group. Mucosal Ki-67 indices of both MSC injected groups were higher than those in the control group. Although caspase-3 positive cells in the mucosa gradually in creased and decreased in the control group, those in both MSC injected groups increased rapidly and decreased thereafter. Conclusion: We demonstrated the effects of regional MSC injection treatment for radiation-induced proctitis in rats. MSC injec tion reduced fibrosis and increased proliferation in rat mucosa. Human AD-MSCs and PD-MSCs had similar effectiveness.
Abstract
Purpose: There are no effective treatment methods with which to control complications of radiation proctitis with fistula or re current bleeding following radiation treatment for prostate, cervical, or rectal cancer. Mesenchymal stem cells (MSCs) can induce immune modification, resulting in tissue repair and regeneration. Therefore, we used a rat model of radiation-induced proctitis and observed the effects of using human placenta-derived (PD) and adipose tissue-derived (AD) MSCs. Materials and Methods: Female Sprague Dawley rats were irradiated at the pelvic area with 25 Gy. We injected 1×106 cells of hu man PD-MSCs, human AD-MSCs, human foreskin fibroblasts, and control media into the rectal submucosa following irradia tion. We sacrificed rats for pathologic evaluation. Results: Fibrosis on the rectum was reduced in both MSC groups, compared to the control group. Mucosal Ki-67 indices of both MSC injected groups were higher than those in the control group. Although caspase-3 positive cells in the mucosa gradually in creased and decreased in the control group, those in both MSC injected groups increased rapidly and decreased thereafter. Conclusion: We demonstrated the effects of regional MSC injection treatment for radiation-induced proctitis in rats. MSC injec tion reduced fibrosis and increased proliferation in rat mucosa. Human AD-MSCs and PD-MSCs had similar effectiveness.
참고문헌 (24)
- Mallick S, "Radiation induced cystitis and proctitis-prediction, assessment and management", Asian Pac J Cancer Prev, 16, pp.5589~5594 (2015)
- Karamanolis G, "Argon plasma coagulation has a long-lasting therapeutic effect in patients with chronic radiation proctitis", Endoscopy, 41, pp.529~531 (2009)
- Linard C, "Repeated autologous bone marrow-derived mesenchymal stem cell injections improve radiation-induced proctitis in pigs", Stem Cells Transl Med, 11, pp.916~927 (2013)
- Ono M, "Effects of human amnion-derived mesenchymal stromal cell transplantation in rats with radiation proctitis", Cytotherapy, 17, pp.1545~1559 (2015)
- Benderitter M, "Stem cell therapies for the treatment of radiation-induced normal tissue side effects", Antioxid Redox Signal, 21, pp.338~355 (2014)
- Kan S, "A rat model for radiation-induced proctitis", J Korean Med Sci, 15, pp.682~689 (2000)
- Choi YJ, "Umbilical cord", placenta-derived mesenchymal stem cells inhibit fibrogenic activation in human intestinal myofibroblasts via inhibition of myocardin-related transcription factor A, 2019, pp.10, 291~
- Kumar H, "Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain : 1-year follow-up of a phase I study", Stem Cell Res Ther, 8, pp.262~ (2017)
- Symon Z, "A murine model for the study of molecular pathogenesis of radiation proctitis", Int J Radiat Oncol Biol Phys, 76, pp.242~250 (2010)
- Dryden GW, "Overview of stem cell therapy for Crohn’s disease", Expert Opin Biol Ther, 9, pp.841~847 (2009)
- Duijvestein M, "Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn’s disease : results of a phase I study", Gut, 59, pp.1662~1669 (2010)
- Lee MJ, "Anti-fibrotic effect of chorionic plate-derived mesenchymal stem cells isolated from human placenta in a rat model of CCl(4)-injured liver : potential application to the treatment of hepatic diseases", J Cell Biochem, 111, pp.1453~1463 (2010)
- Charwat S, "Role of adult bone marrow stem cells in the repair of ischemic myocardium : current state of the art", Exp Hematol, 36, pp.672~680 (2008)
- Kudo K, "Transplantation of mesenchymal stem cells to prevent radiationinduced intestinal injury in mice", J Radiat Res, 51, pp.73~79 (2010)
- Sémont A, "Mesenchymal stem cell therapy stimulates endogenous host progenitor cells to improve colonic epithelial regeneration", PLoS One, 8, pp.e70170~ (2013)
- Saha S, "Bone marrow stromal cell transplantation mitigates radiation-induced gastrointestinal syndrome in mice", PLoS One, 6, pp.e24072~ (2011)
- Gao Z, "Mesenchymal stromal cell-conditioned medium prevents radiation-induced small intestine injury in mice", Cytotherapy, 14, pp.267~273 (2012)
- Wang R, "An experimental study of preventing and treating acute radioactive enteritis with human umbilical cord mesenchymal stem cells", Asian Pac J Trop Med, 6, pp.968~971 (2013)
- Chang P, "Multi-therapeutic effects of human adipose-derived mesenchymal stem cells on radiation-induced intestinal injury", Cell Death Dis, 4, pp.e685~ (2013)
- Northway MG, "Radiation proctitis in the rat. Sequential changes and effects of anti-inflammatory agents", Cancer, 62, pp.1962~1969 (1988)
- Mouiseddine M, "Human mesenchymal stem cells home specifically to radiation-injured tissues in a non-obese diabetes", severe combined immunodeficiency mouse model, 2007, pp.80(Spec No 1), S49~S55
- Jung J, "Epigenetic alterations of IL-6", STAT3 signaling by placental stem cells promote hepatic regeneration in a rat model with CCl4-induced liver injury, 2015, pp.8, 79~89
- Bucci B, "Fractionated ionizing radiation exposure induces apoptosis through caspase-3 activation and reactive oxygen species generation", Anticancer Res, 26, pp.4549~4557 (2006)
- Michelin S, "Increased activity and involvement of caspase-3 in radiation-induced apoptosis in neural cells precursors from developing rat brain", Neurotoxicology, 25, pp.387~398 (2004)