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

Dimitrios Kouroupis; Athena Kyrkou; Eleni Triantafyllidi; Michalis Katsimpoulas; George Chapelakis; Anna Goussia; Anastasios Georgoulis; Carol Murphy; Theodore Fotsis

doi:10.1016/j.scr.2016.04.016

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

Dimitrios Kouroupis
, Athena Kyrkou
, Eleni Triantafyllidi
, Michalis Katsimpoulas
, George Chapelakis
, Anna Goussia
, Anastasios Georgoulis
, Carol Murphy
, Theodore Fotsis

Biosciences

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

438 Downloads (Pure)

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 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.

Original language	English
Journal	Stem Cell Research
Early online date	22 Apr 2016
DOIs	https://doi.org/10.1016/j.scr.2016.04.016
Publication status	E-pub ahead of print - 22 Apr 2016

Keywords

human induced pluripotent stem cells
bioartificial ACL graft
tissue engineering
biomaterials
Anterior cruciate ligament reconstruction
Human adipose tissue multipotential stromal cells

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

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 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.",

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author = "Dimitrios Kouroupis and Athena Kyrkou and Eleni Triantafyllidi and Michalis Katsimpoulas and George Chapelakis and Anna Goussia and Anastasios Georgoulis and Carol Murphy and Theodore Fotsis",

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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 - Chapelakis, George

AU - Goussia, Anna

AU - Georgoulis, Anastasios

AU - Murphy, Carol

AU - Fotsis, Theodore

PY - 2016/4/22

Y1 - 2016/4/22

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 - human induced pluripotent stem cells

KW - bioartificial ACL graft

KW - tissue engineering

KW - biomaterials

KW - Anterior cruciate ligament reconstruction

KW - Human adipose tissue multipotential stromal cells

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DO - 10.1016/j.scr.2016.04.016

M3 - Article

SN - 1873-5061

JO - Stem Cell Research

JF - Stem Cell Research

ER -

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

Abstract

Keywords

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