title: Mensenchymal stem cells can delay radiation-induced crypt death: impact on intestinal CD44(+) fragments.
abstract: Intestinal stem cells are primitive cells found within the intestinal epithelium that play a central role in maintaining epithelial homeostasis through self-renewal and commitment into functional epithelial cells. Several markers are available to identify intestinal stem cells, such as Lgr5, CD24 and EphB2, which can be used to sort intestinal stem cells from mammalian gut. Here, we identify and isolate intestinal stem cells from C57BL/6 mice by using a cell surface antigen, CD44. In vitro, some CD44(+) crypt cells are capable of forming "villus-crypt"-like structures (organoids). A subset strongly positive for CD44 expresses high levels of intestinal stem-cell-related genes, including Lgr5, Bmi1, Hopx, Lrig1, Ascl2, Smoc2 and Rnf43. Cells from this subset are more capable of developing into organoids in vitro, compared with the subset weakly positive for CD44. However, the organoids are sensitive to ionizing irradiation. We investigate the specific roles of mesenchymal stem cells in protecting organoids against radiation-induced crypt death. When co-cultured with mesenchymal stem cells, the crypt domains of irradiated organoids possess more proliferative cells and fewer apoptotic cells than those not co-cultured with mesenchymal stem cells. Cd44v6 continues to be expressed in the crypt domains of irradiated organoids co-cultured with mesenchymal stem cells. Our results indicate specific roles of mesenchymal stem cells in delaying radiation-induced crypt death in vitro.
authors.affiliation: Department of Radiation Oncology, The First Bethune Hospital of Jilin University, Changchun, 130021, People's Republic of China.|Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130000, People's Republic of China.
authors.forename: Peng-Yu
authors.initials: PY
authors.lastname: Chang
authors.affiliation: Ever Union Biotechology, Tianjin, 300162, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Cardiac Surgery, TEDA International Cardiovascular Hospital, Tianjin, 300000, People's Republic of China.
authors.forename: Yi-Yao
authors.initials: YY
authors.lastname: Jiang
authors.affiliation: Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300300, People's Republic of China.
authors.forename: Li-Xian
authors.initials: LX
authors.lastname: Wang
authors.affiliation: Alliancells Bioscience, Tianjin, 300300, People's Republic of China. andyliuliu2001@yahoo.com.cn.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130000, People's Republic of China. jin.d.wang@gmail.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D051927:CD24 Antigen / Q000378:metabolism; D016923:Cell Death / Q000528:radiation effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000528:radiation effects*; D007421:Intestine, Small / Q000528:radiation effects*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009940:Organoids / Q000166:cytology / Q000528:radiation effects; D011837:Radiation-Protective Agents; D036183:Receptor, EphB2 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051927:CD24 Antigen; C497890:Cd24a protein, mouse; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; C493597:Lgr5 protein, mouse; D011837:Radiation-Protective Agents; D043562:Receptors, G-Protein-Coupled; C586311:Ephb2 protein, mouse; D036183:Receptor, EphB2
keywords: CD44; Crypt domains; Mesenchymal stem cell; Organoids; Radiation-induced death