title: Different expression patterns of growth factors in rat fetuses with spina bifida aperta after in utero mesenchymal stromal cell transplantation.
abstract: OBJECTIVE
  In a previous study, we successfully devised a prenatal surgical approach and transplanted mesenchymal stromal cells (MSCs) to fetal rat spinal column to treat retinoic acid-induced neural tube defects in rat. Our results show that MSCs survived, migrated and differentiated into neural lineage cells. We intended to study various growth factor expressions in rat fetal spinal cords with spina bifida aperta after in utero MSC transplantation and the effect of in vivo growth factor introduction for prenatal spina bifida treatment.
  
  
  METHODS
  Pregnant rats were treated with retinoic acid on embryonic day 10 and then received fetal surgery for MSC transplantation and/or lentiviral epidermal growth factor (EGF) injection on embryonic day 16; various growth factor expression in spinal cords from embryonic day 20 fetuses were analyzed by means of quantitative reverse transcriptase-polymerase chain reaction. Terminal deoxynucleotidyl transferase dUTP nick end labeling analysis was performed to observe spinal tissue apoptosis.
  
  
  RESULTS
  Growth factor expression was dysregulated in spinal cords with spina bifida. After MSC transplantation, we observed significantly increased expression of EGF, fibroblast growth factor (FGF)-8, FGF-2 and FGF-20 in the MSC transplantation group compared with blank injection; Furthermore, EGF expression positively correlated with surviving MSC amounts. Expression of other growth factors was not significantly different. In vivo EGF introduction reduced spinal tissue apoptosis.
  
  
  CONCLUSIONS
  Our results suggest that intrinsic EGF and FGF-2, FGF-8 and FGF-20 might affect the in vivo fate of transplanted MSCs in a fetal rat spina bifida model. In vivo EGF introduction together with MSC transplantation might serve as a new strategy for prenatal spina bifida treatment.
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Miao
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Guifeng
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wei
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Songying
authors.initials: S
authors.lastname: Cao
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gu
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China. Electronic address: yuanzw@hotmail.com.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000502:physiology* / Q000601:surgery; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics; D016086:Lentivirus / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D016137:Spina Bifida Cystica / Q000628:therapy*; D013131:Spine / Q000502:physiology* / Q000601:surgery; D059467:Transcriptome; D019076:Transgenes / Q000235:genetics; D014212:Tretinoin / Q000008:administration & dosage; D014599:Uterus / Q000601:surgery
chemical_list: D014212:Tretinoin; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor
keywords: growth factors; in utero MSC transplantation; mesenchymal stromal cells; neural tube defects; prenatal treatment