title: Transplantation of bone marrow mesenchymal stem cells on collagen scaffolds for the functional regeneration of injured rat uterus.
abstract: Serious injuries of endometrium in women of reproductive age are often followed by uterine scar formation and a lack of functional endometrium predisposing to infertility or miscarriage. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown great promise in clinical applications. In the present study, BM-MSCs loaded onto degradable collagen membranes were constructed. Collagen membranes provided 3-dimmensional architecture for the attachment, growth and migration of rat BM-MSCs and did not impair the expression of the stemness genes. We then investigated the effect of collagen/BM-MSCs constructs in the healing of severe uterine injury in rats (partial full thickness uterine excision). At four weeks after the transplantation of collagen/BM-MSCs constructs, BM-MSCs were mainly located to the basal membrane of regenerative endometrium. The wounded tissue adjacent to collagen/BM-MSCs constructs expressed higher level of bFGF, IGF-1, TGFβ1 and VEGF than the corresponding tissue in rats receiving collagen construct alone or in spontaneous regeneration group. Moreover, the collagen/BM-MSCs system increased proliferative abilities of uterine endometrial and muscular cells, facilitated microvasculature regeneration, and restored the ability of endometrium to receive the embryo and support its development to a viable stage. Our findings indicate that BM-MSCs may support uterine tissue regeneration.
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Rd., Nanjing 210008, China; Nanjing Center for Stem Cells and Biomaterials, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Rd., Nanjing 210008, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Rd., Nanjing 210008, China.
authors.forename: Xin'an
authors.initials: X
authors.lastname: Li
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Rd., Nanjing 210008, China.
authors.forename: Haixiang
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Rd., Nanjing 210008, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Rd., Nanjing 210008, China.
authors.forename: Nacheng
authors.initials: N
authors.lastname: Lin
authors.affiliation: Center for Regenerative Medicine, University of Edinburgh, Edinburgh, EH16 4UU, UK.
authors.forename: Bruno
authors.initials: B
authors.lastname: Péault
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Rd., Nanjing 210008, China.
authors.forename: Tianran
authors.initials: T
authors.lastname: Song
authors.affiliation: Department of Pathology, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, 321 Zhongshan Rd. Nanjing 210008, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Nanjing Center for Stem Cells and Biomaterials, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Rd., Nanjing 210008, China; Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing 100190, China. Electronic address: jwdai@genetics.ac.cn.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Rd., Nanjing 210008, China; Nanjing Center for Stem Cells and Biomaterials, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Rd., Nanjing 210008, China; Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Rd., Nanjing 210008, China. Electronic address: yalihu@nju.edu.cn.
authors.forename: Yali
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D003094:Collagen / Q000737:chemistry*; D004717:Endometrium / Q000378:metabolism; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014599:Uterus / Q000166:cytology* / Q000293:injuries*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C548904:insulin-like growth factor-1, rat; C467498:vascular endothelial growth factor A, rat; D007334:Insulin-Like Growth Factor I; D003094:Collagen
keywords: Bone marrow-derived mesenchymal stem cells; Collagen scaffold; Microvasculature; Uterine regeneration