Generation of stem cell-based bioartificial anterior cruciate ligament (ACL) grafts for effective ACL rupture repair

Stem Cell Res. 2016 Sep;17(2):448-457. doi: 10.1016/j.scr.2016.04.016. Epub 2016 Apr 22.

Abstract

In the present study, we combined stem cell technology with a non-absorbable biomaterial for the reconstruction of the ruptured ACL. Towards this purpose, multipotential stromal cells derived either from subcutaneous human adipose tissue (hAT-MSCs) or from induced pluripotent stem cells (iPSCs) generated from human foreskin fibroblasts (hiPSC-MSCs) were cultured on the biomaterial for 21days in vitro to generate a 3D bioartifical ACL graft. Stem cell differentiation towards bone and ligament at the ends and central part of the biomaterial was selectively induced using either BMP-2/FGF-2 or TGF-β/FGF-2 combinations, respectively. The bioartificial ACL graft was subsequently implanted in a swine ACL rupture model in place of the surgically removed normal ACL. Four months post-implantation, the tissue engineered ACL graft generated an ACL-like tissue exhibiting morphological and biochemical characteristics resembling those of normal ACL.

Keywords: Anterior cruciate ligament reconstruction; Bioartificial ACL graft; Biomaterials; Human adipose tissue multipotential stromal cells; Human induced pluripotent stem cells; Tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Anterior Cruciate Ligament / diagnostic imaging
  • Anterior Cruciate Ligament / pathology
  • Anterior Cruciate Ligament Injuries / diagnostic imaging
  • Anterior Cruciate Ligament Injuries / pathology
  • Anterior Cruciate Ligament Injuries / therapy*
  • Anterior Cruciate Ligament Injuries / veterinary
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism
  • Cell Differentiation
  • Cellular Reprogramming
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Foreskin / cytology
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / transplantation
  • Male
  • Mesoderm / metabolism
  • Mesoderm / pathology
  • Models, Animal
  • Positron Emission Tomography Computed Tomography
  • Stromal Cells / cytology
  • Stromal Cells / metabolism
  • Stromal Cells / transplantation*
  • Swine

Substances

  • Bone Morphogenetic Protein 2
  • Fibroblast Growth Factor 2