Tissue engineering approaches for treating pelvic organ prolapse using a novel source of stem/stromal cells and new materials

Curr Opin Urol. 2019 Jul;29(4):450-457. doi: 10.1097/MOU.0000000000000634.

Abstract

Purpose of review: Nondegradable transvaginal polypropylene meshes for treating pelvic organ prolapse (POP) are now generally unavailable or banned. In this review, we summarize recent developments using tissue engineering approaches combining alternate degradable scaffolds with a novel source of mesenchymal stem/stromal cells from human endometrium (eMSC).

Recent findings: Tissue engineering constructs comprising immunomodulatory, reparative eMSC and biomimetic materials with nanoarchitecture are a promising approach for vaginal repair and improving outcomes of POP surgery. Culture expansion of eMSC that maintains them (and other MSC) in the undifferentiated state has been achieved using a small molecule transforming growth factor-β receptor inhibitor, A83-01. The mechanism of action of A83-01 has been determined and its suitability for translation into the clinic explored. Novel blends of electrospun synthetic and natural polymers combined with eMSC shows this approach promotes host cell infiltration and slows biomaterial degradation that has potential to strengthen the vaginal wall during healing. Improving the preclinical ovine transvaginal surgical model by adapting the human clinical POP-Quantification system for selection of multiparous ewes with vaginal wall weakness enables assessment of this autologous eMSC/nanobiomaterial construct.

Summary: A tissue engineering approach using autologous eMSC with degradable nanobiomaterials offers a new approach for treating women with POP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Absorbable Implants
  • Animals
  • Disease Models, Animal
  • Endometrium / cytology
  • Female
  • Humans
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / immunology
  • Nanostructures / therapeutic use
  • Pelvic Organ Prolapse / surgery*
  • Pyrazoles / pharmacology
  • Receptors, Transforming Growth Factor beta / antagonists & inhibitors
  • Sheep
  • Stromal Cells / transplantation*
  • Surgical Mesh
  • Thiosemicarbazones / pharmacology
  • Tissue Engineering / methods*
  • Tissue Scaffolds
  • Transplantation, Autologous
  • Vagina / surgery

Substances

  • A-83-01
  • Pyrazoles
  • Receptors, Transforming Growth Factor beta
  • Thiosemicarbazones