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Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model.

Desando G, Cavallo C, Sartoni F, Martini L, Parrilli A, Veronesi F, Fini M, Giardino R, Facchini A, Grigolo B - Arthritis Res. Ther. (2013)

Bottom Line: Intra-articular ASC administration decreases OA progression and exerts a healing contribution in the treated animals in comparison to OA and 4% RSA groups.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.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: 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.

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Histological evaluation of synovial membrane in OA, 4% RSA and ASC-treated groups. (A) H/E staining of representative specimens. Scale bars = 100 μm. (B) Laverty's score. Data are reported in terms of the 95% confidence intervals. Statistical values of at least P < 0.01 were observed in all the comparisons.
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Figure 6: Histological evaluation of synovial membrane in OA, 4% RSA and ASC-treated groups. (A) H/E staining of representative specimens. Scale bars = 100 μm. (B) Laverty's score. Data are reported in terms of the 95% confidence intervals. Statistical values of at least P < 0.01 were observed in all the comparisons.

Mentions: Synovial tissue after ACLT in OA group displayed at eight weeks thickening of the lining layer and evidence of infiltration by inflammatory cells. A progression of the pathology was detected in the 4% RSA group at 16 and 24 weeks with an increase of Laverty's score compared to the OA group (P < 0.01). ASC administration (2 × 106 and 6 × 106) significantly decreased Laverty's score at 16 and 24 weeks compared to the 4% RSA and OA groups (P < 0.01). The protective effects exerted by the ASCs were noticed overall in reducing the thickness of the lining layer and the infiltration of inflammatory cells in the sub-synovium. In particular, best results were noticed in the 6 × 106 ASC-treated group at 16 weeks compared to 24 weeks (P < 0.01) (Figure 6A, B). An histological analysis on menisci was performed in order to determine if ASC treatment had an effect on the meniscal compartment. A significant increase of cell cluster was noticed in the 4% RSA at 16 and 24 weeks compared to the OA group (P < 0.01). The 2 × 106 and 6 × 106 ASC-treated groups displayed a well organized tissue with a low number of cell clusters at 16 and 24 weeks compared to the OA and 4% RSA groups at both experimental times (P < 0.01) (Figure 7A, B).


Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model.

Desando G, Cavallo C, Sartoni F, Martini L, Parrilli A, Veronesi F, Fini M, Giardino R, Facchini A, Grigolo B - Arthritis Res. Ther. (2013)

Histological evaluation of synovial membrane in OA, 4% RSA and ASC-treated groups. (A) H/E staining of representative specimens. Scale bars = 100 μm. (B) Laverty's score. Data are reported in terms of the 95% confidence intervals. Statistical values of at least P < 0.01 were observed in all the comparisons.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672720&req=5

Figure 6: Histological evaluation of synovial membrane in OA, 4% RSA and ASC-treated groups. (A) H/E staining of representative specimens. Scale bars = 100 μm. (B) Laverty's score. Data are reported in terms of the 95% confidence intervals. Statistical values of at least P < 0.01 were observed in all the comparisons.
Mentions: Synovial tissue after ACLT in OA group displayed at eight weeks thickening of the lining layer and evidence of infiltration by inflammatory cells. A progression of the pathology was detected in the 4% RSA group at 16 and 24 weeks with an increase of Laverty's score compared to the OA group (P < 0.01). ASC administration (2 × 106 and 6 × 106) significantly decreased Laverty's score at 16 and 24 weeks compared to the 4% RSA and OA groups (P < 0.01). The protective effects exerted by the ASCs were noticed overall in reducing the thickness of the lining layer and the infiltration of inflammatory cells in the sub-synovium. In particular, best results were noticed in the 6 × 106 ASC-treated group at 16 weeks compared to 24 weeks (P < 0.01) (Figure 6A, B). An histological analysis on menisci was performed in order to determine if ASC treatment had an effect on the meniscal compartment. A significant increase of cell cluster was noticed in the 4% RSA at 16 and 24 weeks compared to the OA group (P < 0.01). The 2 × 106 and 6 × 106 ASC-treated groups displayed a well organized tissue with a low number of cell clusters at 16 and 24 weeks compared to the OA and 4% RSA groups at both experimental times (P < 0.01) (Figure 7A, B).

Bottom Line: Intra-articular ASC administration decreases OA progression and exerts a healing contribution in the treated animals in comparison to OA and 4% RSA groups.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.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: 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.

Show MeSH
Related in: MedlinePlus