Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model.
BACKGROUND
Cell therapy is a rapidly growing area of research for the treatment of osteoarthritis (OA). This work is aimed to investigate the efficacy of intra-articular adipose-derived stromal cell (ASC) injection in the healing process on cartilage, synovial membrane and menisci in an experimental rabbit model.


METHODS
The induction of OA was performed surgically through bilateral anterior cruciate ligament transection (ACLT) to achieve eight weeks from ACLT a mild grade of OA. A total of 2×10⁶ and 6×10⁶ autologous ASCs isolated from inguinal fat, expanded in vitro and suspended in 4% rabbit serum albumin (RSA) were delivered in the hind limbs; 4% RSA was used as the control. Local bio-distribution of the cells was verified by injecting chloro-methyl-benzamido-1,1'-dioctadecyl-3,3,3'3'-tetra-methyl-indo-carbocyanine per-chlorate (CM-Dil) labeled ASCs in the hind limbs. Cartilage and synovial histological sections were scored by Laverty's scoring system to assess the severity of the pathology. Protein expression of some extracellular matrix molecules (collagen I and II), catabolic (metalloproteinase-1 and -3) and inflammatory (tumor necrosis factor- α) markers were detected by immunohistochemistry. Assessments were carried out at 16 and 24 weeks.


RESULTS
Labeled-ASCs were detected unexpectedly in the synovial membrane and medial meniscus but not in cartilage tissue at 3 and 20 days from ASC-treatment. Intra-articular ASC administration decreases OA progression and exerts a healing contribution in the treated animals in comparison to OA and 4% RSA groups.


CONCLUSIONS
Our data reveal a healing capacity of ASCs in promoting cartilage and menisci repair and attenuating inflammatory events in synovial membrane inhibiting OA progression. On the basis of the local bio-distribution findings, the benefits obtained by ASC treatment could be due to a trophic mechanism of action by the release of growth factors and cytokines.
Giovanna
G
Desando
Carola
C
Cavallo
Federica
F
Sartoni
Lucia
L
Martini
Annapaola
A
Parrilli
Francesca
F
Veronesi
Milena
M
Fini
Roberto
R
Giardino
Andrea
A
Facchini
Brunella
B
Grigolo
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology / Q000628:therapy*; D018450:Disease Progression; D007270:Injections, Intra-Articular; D008297:Male; D020370:Osteoarthritis, Knee / Q000473:pathology* / Q000628:therapy*; D011817:Rabbits; D017154:Stromal Cells / Q000637:transplantation*