TY - JOUR
T1 - Generation of stem cell-based bioartificial anterior cruciate ligament (ACL) grafts for effective ACL rupture repair
AU - Kouroupis, Dimitrios
AU - Kyrkou, Athena
AU - Triantafyllidi, Eleni
AU - Katsimpoulas, Michalis
AU - Chalepakis, George
AU - Goussia, Anna
AU - Georgoulis, Anastasios
AU - Murphy, Carol
AU - Fotsis, Theodore
N1 - Publisher Copyright:
© 2016 Helmholtz Zentrum München
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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 21 days 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.
AB - 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 21 days 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.
KW - Anterior cruciate ligament reconstruction
KW - Bioartificial ACL graft
KW - Biomaterials
KW - Human adipose tissue multipotential stromal cells
KW - Human induced pluripotent stem cells
KW - Tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=84969528791&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84969528791&partnerID=8YFLogxK
U2 - 10.1016/j.scr.2016.04.016
DO - 10.1016/j.scr.2016.04.016
M3 - Article
C2 - 27217303
AN - SCOPUS:84969528791
VL - 17
SP - 448
EP - 457
JO - Stem Cell Research
JF - Stem Cell Research
SN - 1873-5061
IS - 2
ER -