title: Directional delivery of RSPO1 by mesenchymal stem cells ameliorates radiation-induced intestinal injury.
abstract: Radiation-induced intestinal injury (RIII) commonly occurs in patients who received radiotherapy for pelvic or abdominal cancer, or who suffered from whole-body irradiation during a nuclear accident. RIII can lead to intestinal disorders and even death given its integrity damage that results from intestinal stem cell (ISC) loss. Recovery from RIII relies on the intensity of supportive treatment, which can attenuate lethal infection and give surviving stem cells an opportunity to regenerate. It has been reported that RSPO1 is a cytokine with potent and specific proliferative effects on intestinal crypt cells. MSCs have multiple RIII-healing effects, including anti-inflammatory and anti-irradiation injury properties, due to its negative immune regulation and its homing ability to the damaged intestinal epithelia. To combine the comprehensive anti-injury potential of MSCs, and the potent ability of RSPO1 as a mitogenic factor for ISCs, we constructed RSPO1-modified C3H10 T1/2 cells and expected that RSPO1, the ISC-proliferative cytokine, could be delivered to the site of injury in a targeted manner. In this study, we transferred C3H10/RSPO1 intravenously via the retro-orbital sinus into mice suffering from abdominal irradiation at lethal dosages. Our findings demonstrated that C3H10/RSPO1 cells are able to directionally migrate to the injury site; enhance ISC survival, proliferation, and differentiation; and effectively repair the radiation-damaged intestinal epithelial cells. This study suggests that the directional delivery of RSPO1 by MSCs is a promising strategy to ameliorate, and even cure, RIII.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou 215000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Suzhou Digestive Diseases and Nutrition Research Center, Affiliated Suzhou Hospital of Nanjing Medical University, North District of Suzhou Municipal Hospital, Suzhou 215008, China.
authors.forename: Songwen
authors.initials: S
authors.lastname: Ju
authors.affiliation: Department of Immunology, School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou 215000, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Immunology, School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou 215000, China.
authors.forename: Yongfang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Immunology, School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou 215000, China.
authors.forename: Xiaocui
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Immunology, School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou 215000, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Immunology, School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou 215000, China. Electronic address: geyanmd2004@sina.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Department of Immunology, School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou 215000, China. Electronic address: songguang_ju@hotmail.com.
authors.forename: Songguang
authors.initials: S
authors.lastname: Ju
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000502:physiology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000276:immunology / Q000628:therapy*; D012038:Regeneration; D013234:Stem Cells / Q000502:physiology; D019699:Thrombospondins / Q000235:genetics*; D014162:Transfection; D000098907:R-Spondins
chemical_list: D019699:Thrombospondins; C503243:RSPO1 protein, human; D000098907:R-Spondins
keywords: Intestinal crypt stem cells; Irradiation; LGR5; Mesenchymal stem cell; R-spondin1