TY - JOUR
T1 - Osteogenic potential of human adipose-tissue-derived mesenchymal stromal cells cultured on 3D-printed porous structured titanium
AU - Lewallen, Eric A.
AU - Jones, Dakota L.
AU - Dudakovic, Amel
AU - Thaler, Roman
AU - Paradise, Christopher R.
AU - Kremers, Hilal M.
AU - Abdel, Matthew P.
AU - Kakar, Sanjeev
AU - Dietz, Allan B.
AU - Cohen, Robert C.
AU - Lewallen, David G.
AU - van Wijnen, Andre J
N1 - Funding Information:
We thank members of the van Wijnen and Dietz Laboratories, especially Matthew Getzlaf and Darcie Radel, as well as Scott Riester, Emily Camilleri, and Janet Denbeigh, for stimulating discussions and/or assistance with reagents and procedures. The Biomaterials Characterization and Quantitative Histomorphometry Core Laboratory facility performed histological analysis, particularly Bob Brown and Jim Herrick. We are grateful to Scott Gamb and the Electron Microscopy Core facility for their assistance with acquiring scanning electron microscopy images. We thank the Reconstructive Research and Development group at Stryker Orthopedics, particularly Brent Mitchell, Dale Swarts, and Mark Gruczynski, for manufacturing biomaterials used in this study. Financial support for this work came from the National Institute of Arthritis and Musculoskeletal and Skin Diseases ( R01 AR049069 to Andre van Wijnen ; T32 AR56950 to Eric Lewallen; and F32 AR066508 to Amel Dudakovic). We also appreciate the generous philanthropic support of William H. and Karen J. Eby, and the charitable foundation in their names. The following author disclosures are provided regarding affiliations that may be perceived to bias the presentation of this work: ABD has commercial interest in Mill Creek Life Sciences, which manufactures the clinical-grade commercial platelet lysate product used for maintaining adipose-tissue-derived mesenchymal stem cells. RCC serves as the vice president and general manager of Reconstructive Research and Development, Stryker Orthopedics, 325 Corporate Drive, Mahwah, NJ 07430. DGL reports personal fees and other from Stryker, Pipeline Biomedical, Zimmer, and Ketai Medical Devices. In addition, DGL has patents on selected hip and knee implants with royalties paid by Zimmer and is employed part time as the Medical Director for the American Joint Replacement registry.
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Integration of porous metal prosthetics, which restore form and function of irreversibly damaged joints, into remaining healthy bone is critical for implant success. We investigated the biological properties of adipose-tissue-derived mesenchymal stromal/stem cells (AMSCs) and addressed their potential to alter the in vitro microenvironment of implants. We employed human AMSCs as a practical source for musculoskeletal applications because these cells can be obtained in large quantities, are multipotent, and have trophic paracrine functions. AMSCs were cultured on surgical-grade porous titanium disks as a model for orthopedic implants. We monitored cell/substrate attachment, cell proliferation, multipotency, and differentiation phenotypes of AMSCs upon osteogenic induction. High-resolution scanning electron microscopy and histology revealed that AMSCs adhere to the porous metallic surface. Compared to standard tissue culture plastic, AMSCs grown in the porous titanium microenvironment showed differences in temporal expression for genes involved in cell cycle progression (CCNB2, HIST2H4), extracellular matrix production (COL1A1, COL3A1), mesenchymal lineage identity (ACTA2, CD248, CD44), osteoblastic transcription factors (DLX3, DLX5, ID3), and epigenetic regulators (EZH1, EZH2). We conclude that metal orthopedic implants can be effectively seeded with clinical-grade stem/stromal cells to create a pre-conditioned implant.
AB - Integration of porous metal prosthetics, which restore form and function of irreversibly damaged joints, into remaining healthy bone is critical for implant success. We investigated the biological properties of adipose-tissue-derived mesenchymal stromal/stem cells (AMSCs) and addressed their potential to alter the in vitro microenvironment of implants. We employed human AMSCs as a practical source for musculoskeletal applications because these cells can be obtained in large quantities, are multipotent, and have trophic paracrine functions. AMSCs were cultured on surgical-grade porous titanium disks as a model for orthopedic implants. We monitored cell/substrate attachment, cell proliferation, multipotency, and differentiation phenotypes of AMSCs upon osteogenic induction. High-resolution scanning electron microscopy and histology revealed that AMSCs adhere to the porous metallic surface. Compared to standard tissue culture plastic, AMSCs grown in the porous titanium microenvironment showed differences in temporal expression for genes involved in cell cycle progression (CCNB2, HIST2H4), extracellular matrix production (COL1A1, COL3A1), mesenchymal lineage identity (ACTA2, CD248, CD44), osteoblastic transcription factors (DLX3, DLX5, ID3), and epigenetic regulators (EZH1, EZH2). We conclude that metal orthopedic implants can be effectively seeded with clinical-grade stem/stromal cells to create a pre-conditioned implant.
KW - Biomaterial
KW - Extracellular matrix
KW - Gene expression
KW - Mesenchymal stem cell
KW - Scanning electron microscopy
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U2 - 10.1016/j.gene.2016.01.015
DO - 10.1016/j.gene.2016.01.015
M3 - Article
C2 - 26774799
AN - SCOPUS:84958768001
SN - 0378-1119
VL - 581
SP - 95
EP - 106
JO - Gene
JF - Gene
IS - 2
ER -