Abstract

Localized cartilage lesions in early osteoarthritis and acute joint injuries are usually treated surgically to restore function and relieve pain. However, a persistent clinical challenge remains in how to repair the cartilage lesions. We expressed doublecortin (DCX) in human adipose-derived stromal/stem cells (hASCs) and engineered hASCs into cartilage tissues using an in vitro 96-well pellet culture system. The cartilage tissue constructs with and without DCX expression were implanted in the knee cartilage defects of rabbits (n = 42) and monkeys (n = 12). Cohorts of animals were euthanized at 6, 12, and 24 months after surgery to evaluate the cartilage repair outcomes. We found that DCX expression in hASCs increased expression of growth differentiation factor 5 (GDF5) and matrilin 2 in the engineered cartilage tissues. The cartilage tissues with DCX expression significantly enhanced cartilage repair as assessed macroscopically and histologically at 6, 12, and 24 months after implantation in the rabbits and 24 months after implantation in the monkeys, compared to the cartilage tissues without DCX expression. These findings suggest that hASCs expressing DCX may be engineered into cartilage tissues that can be used to treat localized cartilage lesions.

Details

Title
Human adipose-derived stromal/stem cells expressing doublecortin improve cartilage repair in rabbits and monkeys
Author
Ge Dongxia 1 ; O’Brien Michael J 2   VIAFID ORCID Logo  ; Savoie, Felix H 2 ; Gimble, Jeffrey M 3 ; Wu Xiying 4 ; Gilbert, Margaret H 5 ; Clark-Patterson, Gabrielle L 6 ; Schuster, Jason D 6 ; Miller, Kristin S 6 ; Wang, Alun 7 ; Myers, Leann 8 ; You Zongbing 9   VIAFID ORCID Logo 

1  Tulane University School of Medicine, Department of Structural and Cellular Biology, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588); Tulane University School of Medicine, Department of Orthopaedic Surgery, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588) 
2  Tulane University School of Medicine, Department of Orthopaedic Surgery, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588) 
3  Tulane University School of Medicine, Department of Structural and Cellular Biology, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588); LaCell LLC and Obatala Sciences Inc., New Orleans, USA (GRID:grid.504745.7); Tulane University School of Medicine, Tulane Center for Stem Cell Research and Regenerative Medicine, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588); Tulane University School of Medicine, John W. Deming Department of Medicine, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588); Tulane University School of Medicine, Department of Surgery, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588) 
4  LaCell LLC and Obatala Sciences Inc., New Orleans, USA (GRID:grid.504745.7) 
5  Tulane University, Tulane National Primate Research Center, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588) 
6  Tulane University, Department of Biomedical Engineering, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588) 
7  Tulane University School of Medicine, Department of Pathology and Laboratory Medicine, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588) 
8  Tulane University School of Public Health and Tropic Medicine, Department of Biostatistics and Data Science, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588) 
9  Tulane University School of Medicine, Department of Structural and Cellular Biology, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588); Tulane University School of Medicine, Department of Orthopaedic Surgery, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588); Tulane University School of Medicine, Tulane Center for Stem Cell Research and Regenerative Medicine, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588); Tulane University School of Medicine, Tulane Cancer Center and Louisiana Cancer Research Consortium, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588); Tulane University School of Medicine, Tulane Center for Aging, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588); Southeast Louisiana Veterans Health Care System, New Orleans, USA (GRID:grid.417056.1) (ISNI:0000 0004 0419 6004) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20573995
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41536-021-00192-6
ProQuest document ID
2604660075
Copyright
© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.