Article: Cohen, BP; Bernstein, JL; Morrison, KA; Spector, JA; Bonassar, LJ; “Tissue Engineering the Human Auricle by Auricular Chondrocyte-Mesenchymal Stem Cell Co-Implantation”, PLOS ONE, 13 (10)
Abstract: Children suffering from microtia have few options for auricular reconstruction. Tissue engineering approaches attempt to replicate the complex anatomy and structure of the ear with autologous cartilage but have been limited by access to clinically accessible cell sources. Here we present a full-scale, patient-based human ear generated by implantation of human auricular chondrocytes and human mesenchymal stem cells in a 1:1 ratio. Additional disc construct surrogates were generated with 1:0, 1:1, and 0:1 combinations of auricular chondrocytes and mesenchymal stem cells. After 3 months in vivo, monocellular auricular chondrocyte discs and 1:1 disc and ear constructs displayed bundled collagen fibers in a perichondrial layer, rich proteoglycan deposition, and elastin fiber network formation similar to native human auricular cartilage, with the protein composition and mechanical stiffness of native tissue. Full ear constructs with a 1:1 cell combination maintained gross ear structure and developed a cartilaginous appearance following implantation. These studies demonstrate the successful engineering of a patient-specific human auricle using exclusively human cell sources without extensive in vitro tissue culture prior to implantation, a critical step towards the clinical application of tissue engineering for auricular reconstruction.
Funding Acknowledgement: National Institutes of Health [5T35EB006732]; Empire State Development’s Division of Science, Technology and Innovation; Empire State Stem Cell Fund through New York State Department of Health [C30293GG]; 3D BioCorp; Stem Cell Pathology unit for Scanscope services (NYSTEM) [C029155]
Funding Text: Funding provided by the National Institutes of Health Grant 5T35EB006732 (BPC, JAS, LJB), Empire State Development’s Division of Science, Technology and Innovation (JAS, LJB), Empire State Stem Cell Fund through New York State Department of Health Contract #C30293GG (BPC), and 3D BioCorp (LJB) and the Stem Cell Pathology unit for Scanscope services (NYSTEM grant C029155). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.We thank Drs. Katherine Hudson and Mary Clare McCorry for advisement on use of stem cells, Drs. Charles Thorne and John Sherman for assistance acquiring human auricular cartilage samples, the Cornell Statistical Consulting Unit (CSCU) for consultation on statistical analyses, and the Stem Cell Pathology unit for Scanscope services (NYSTEM grant C029155).