Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis.
BACKGROUND
Mesenchymal stem cells (MSCs) can differentiate into various connective tissue cells. Several techniques have been used for the clinical application of MSCs in articular cartilage repair; however, there are many issues associated with the selection of the scaffold material, including its ability to support cell viability and differentiation and its retention and degradation in situ. The application of MSCs via a scaffold also requires a technically demanding surgical procedure. The aim of this study was to test the outcome of intra-articular transplantation of mesenchymal stem cells suspended in hyaluronic acid (HA) in the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis (OA).


METHODS
Commercially available human MSCs were cultured, labeled with carboxyfluorescein diacetate succinimidyl ester (CFDA-SE), suspended in either PBS or HA, and injected into the knee joints of 7-month-old animals. The control animals were injected with either PBS or HA alone. The animals were sacrificed at 1, 3, and 5 weeks post transplantation, the knee joints harvested, and fluorescent microscopic analysis was performed. Histological and immunohistochemical analysis were performed at 5 weeks post transplantation.


RESULTS
At 5 weeks post transplantation, partial cartilage repair was noted in the HA-MSC group but not in the other groups. Examination of CFDA-SE-labeled cells demonstrated migration, differentiation, and proliferation of MSC in the HA-MSC group. There was strong immunostaining for type II collagen around both residual chondrocytes and transplanted MSCs in the OA cartilage.


CONCLUSIONS
This scaffold-free and technically undemanding technique appears to result in the regeneration of articular cartilage in the spontaneous OA animal model. Although further examination of the long-term effects of transplantation is necessary, the findings suggest that intra-articular injection of HA-MSC mixture is potentially beneficial for OA.
Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui, Matsuoka-Shimoaizuki 23, Eiheiji, Fukui 910-1193, Japan.
Mitsuhiko
M
Sato
Kenzo
K
Uchida
Hideaki
H
Nakajima
Tsuyoshi
T
Miyazaki
Alexander Rodriguez
AR
Guerrero
Shuji
S
Watanabe
Sally
S
Roberts
Hisatoshi
H
Baba
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024043:Collagen Type II / Q000378:metabolism; D005452:Fluoresceins / Q000737:chemistry; D006168:Guinea Pigs; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000494:pharmacology; D015151:Immunoblotting; D007150:Immunohistochemistry; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010003:Osteoarthritis / Q000473:pathology / Q000601:surgery*; D013388:Succinimides / Q000737:chemistry; D014183:Transplantation, Heterologous
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D024043:Collagen Type II; D005452:Fluoresceins; D013388:Succinimides; D006820:Hyaluronic Acid