Improved cartilage regeneration utilizing mesenchymal stem cells in TGF-beta1 gene-activated scaffolds.
Recently, bone marrow-derived mesenchymal stem cells (MSCs) have been paid more attention for cartilage regeneration. This study evaluated the potential of using MSCs seeded in plasmid transforming growth factor beta1 (pTGF-beta1)-activated three-dimensional chitosan/gelatin scaffolds for improving cartilage repair in vivo. Significant cell proliferation and transforming growth factor beta1 protein expression were observed in vitro in pTGFbeta1-activated scaffolds. Transforming growth factor beta1-activated scaffolds showed high collagen type II and aggrecan expression and low collagen type I expression during in vitro cultivation. MSC-based pTGF-beta1-activated scaffolds also exhibited cartilage histology with high secretion of collagen type II in vitro under the stimulation of pTGF-beta1. In rabbits with full-thickness cartilage defects, the implantation of MSC-based pTGF-beta1-activated scaffolds not only significantly promoted chondrogenic differentiation of MSCs and hyalin-like cartilage matrix synthesis, but also remarkably improved the overall repair of rabbit cartilage defects and exhibited favorable tissue integrity at 10 weeks postsurgery. These results suggest that MSC-based localized pTGF-beta1-activated scaffolds have potential applications for in vivo cartilage repair.
Diao
Huajia
H
Department of Orthopaedics Surgery, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Jinling Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, China.
Wang
Jinliang
J
Shen
Chao
C
Xia
Suhua
S
Guo
Ting
T
Dong
Lei
L
Zhang
Chenyu
C
Chen
Jiangning
J
Zhao
Jianning
J
Zhang
Junfeng
J
D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000502:physiology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology; D024043:Collagen Type II / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005780:Gelatin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051457:Hyaline Cartilage / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014945:Wound Healing / Q000187:drug effects
D024043:Collagen Type II; D053773:Transforming Growth Factor beta1; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D005780:Gelatin; D048271:Chitosan