Transplantation of bone marrow mesenchymal stem cells on collagen scaffolds for the functional regeneration of injured rat uterus

Biomaterials. 2014 Jun;35(18):4888-900. doi: 10.1016/j.biomaterials.2014.02.046. Epub 2014 Mar 27.

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.

Keywords: Bone marrow-derived mesenchymal stem cells; Collagen scaffold; Microvasculature; Uterine regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Collagen / chemistry*
  • Endometrium / metabolism
  • Female
  • Insulin-Like Growth Factor I / metabolism
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Regeneration
  • Tissue Engineering*
  • Tissue Scaffolds*
  • Transforming Growth Factor beta1 / metabolism
  • Uterus / cytology*
  • Uterus / injuries*
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / physiology

Substances

  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A
  • insulin-like growth factor-1, rat
  • vascular endothelial growth factor A, rat
  • Insulin-Like Growth Factor I
  • Collagen