Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model

被引:125
作者
Mokbel, Abir N. [2 ]
El Tookhy, Omar S. [3 ]
Shamaa, Ashraf A. [3 ]
Rashed, Laila A. [1 ]
Sabry, Dina [1 ]
El Sayed, Abeer M. [4 ]
机构
[1] Cairo Univ, Fac Med, Dept Med Biochem & Mol Biol, Cairo, Egypt
[2] Cairo Univ, Fac Med, Dept Rheumatol & Rehabil, Cairo, Egypt
[3] Cairo Univ, Fac Vet Med, Dept Surg Anesthesiol & Radiol, Cairo, Egypt
[4] Cairo Univ, Natl Canc Inst, Dept Pathol, Cairo, Egypt
关键词
MSCs; Chondral defect; Intra-articular; Homing; GFP; Repair; Donkeys; EXPERIMENTALLY-INDUCED ARTHRITIS; ARTICULAR-CARTILAGE; DIFFERENTIATION; HYALURONAN; SYNOVITIS; EFFICACY; THERAPY;
D O I
10.1186/1471-2474-12-259
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
100224 [整形外科学];
摘要
Background: This work aimed to study the homing evidence and the reparative effect of mesenchymal stem cells (MSCs) in the healing process of induced osteoarthritis in experimental animal model (donkeys). Methods: Twenty-seven donkeys were equally divided into 3 groups based on the observation period after induction of arthritis (3, 6 and 9 weeks) to achieve different degrees of osteoarthritis. Each group was subdivided into three subgroups of three animals each based on the follow-up period (1, 2 and 6 months) after treatment. The induction was done through intra-articular (IA) injection of 2 ml of Amphotericin-B in both carpal joints. MSCs were harvested in a separate procedure, labeled with green fluorescent protein (GFP) using monster GFP vector and suspended in hyaluronic acid for IA injection. Treatment approaches consisted of cell-treatment using MSCs suspended in 3 ml of hyaluronic acid (HA) for the right carpal joint; and using the same amount of (HA) but without MSCs for the left contralateral carpal joint to serve as a control. Animals were assessed clinically and radiologically before and after treatment. Synovial fluid was also evaluated. Histopathologically; articular cartilage structural changes, reduction of articular cartilage matrix staining, osteophyte formation, and subchondral bone plate thickening were graded. Data was summarized using median and percentile for scores of histopathologic grading. Comparison between groups was done using non-parametric Mann Whitney test. Results: The reparative effect of MSCs was significant both clinically and radiologically in all treated groups (P < 0.05) compared to the control groups. Fluorescence microscopy of sections of the cell-treated joints of all animals indicated that the GFP-transduced injected cells have participated effectively in the reparative process of the damaged articular surface and have integrated within the existing articular cartilage. The cells were associated with the surface of the cartilage and, were also detected in the interior. Conclusions: Homing was confirmed by the incorporation of injected GFP-labeled MSCs within the repaired newly formed cartilage. Significant recovery proves that the use of IA injection of autologous MSCs is a viable and a practical option for treating different degrees of osteoarthritis.
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页数:18
相关论文
共 47 条
[1]
Mechanisms of Disease: role of chondrocytes in the pathogenesis of osteoarthritis - structure, chaos and senescence [J].
Aigner, Thomas ;
Soeder, Stefan ;
Gebhard, Pia M. ;
McAlinden, Audrey ;
Haag, Jochen .
NATURE CLINICAL PRACTICE RHEUMATOLOGY, 2007, 3 (07) :391-399
[2]
*AM PSYCH ASS, 1996, GUID ETH COND CAR US
[3]
Animal models of osteoarthritis: lessons learned while seeking the 'Holy Grail' [J].
Ameye, Laurent G. ;
Young, Marian F. .
CURRENT OPINION IN RHEUMATOLOGY, 2006, 18 (05) :537-547
[4]
ANON J, 1991, GUIDE VET SERVICE JU, P4
[5]
Forced mobilization accelerates pathogenesis: characterization of a preclinical surgical model of osteoarthritis (vol 10, pg 407, 2008) [J].
Appleton, C. Thomas G. ;
McErlain, David D. ;
Pitelka, Vasek ;
Schwartz, Neil ;
Bernier, Suzanne M. ;
Henry, James L. ;
Holdsworth, David W. ;
Beier, Frank .
ARTHRITIS RESEARCH & THERAPY, 2008, 10 (05)
[6]
AYOTTE R, 1969, CAN MED A, V100, P242
[7]
Hyaluronic acid hydrogel in the treatment of osteoarthritis [J].
Barbucci, R ;
Lamponi, S ;
Borzacchiello, A ;
Ambrosio, L ;
Fini, M ;
Torricelli, P ;
Giardino, R .
BIOMATERIALS, 2002, 23 (23) :4503-4513
[8]
Barry Frank P., 2003, Birth Defects Research, V69, P250, DOI 10.1002/bdrc.10021
[9]
BOWMAN KF, 1983, AM J VET RES, V44, P51
[10]
Mesenchymal stem cells as trophic mediators [J].
Caplan, Arnold I. ;
Dennis, James E. .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2006, 98 (05) :1076-1084