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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.

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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 medial femoral condyle in OA, 4% RSA and ASC-treated groups. (A) Safranin-O/Fast Green staining of representative specimens. Black arrows, fibrillation and delamination processes. Red arrows, Erosion processes. Scale bars = 1,000 μm. (B) Laverty's score. Data are reported in terms of 95% confidence intervals. Statistical values of at least P < 0.01 were observed in all the comparisons.
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Figure 5: Histological evaluation of medial femoral condyle in OA, 4% RSA and ASC-treated groups. (A) Safranin-O/Fast Green staining of representative specimens. Black arrows, fibrillation and delamination processes. Red arrows, Erosion processes. Scale bars = 1,000 μm. (B) Laverty's score. Data are reported in terms of 95% confidence intervals. Statistical values of at least P < 0.01 were observed in all the comparisons.

Mentions: A glossy, white cartilage with no degenerative noticeable macroscopic evidence was observed in the ASCS-treated groups at both experimental times. Cartilage softening and fibrillation were instead observed in the OA and 4% RSA groups particularly in the medial regions (data not shown). Histo-morphometric analyses provided further information on the status of the structure of cartilage tissue. Among the pathological changes recorded during OA, an increase of FI was observed in OA group compared to 4% RSA at both 16 and 24 weeks (P < 0.01). A significant reduction of FI was noticed in both ASCs treated groups at 16 weeks compared to 4% RSA at both experimental times (P < 0,01), indicating a protective role of ASCs in reducing fibrillation processes (Figure 4A). The intra-articular delivery of 2 × 106 ASCs revealed an increase of CT values respect the OA group and 4% RSA at 16 and 24 weeks (P < 0.01) (Figure 4B). Based on visual assessment of the histological staining, there were significant, overall effects of ASCs in the healing of cartilaginous tissue which displayed some hyaline features with a smooth surface, a regular cellular arrangement and a high proteoglycan content leading to a functional cartilage tissue (Figure 5A, B). In particular, 2 × 106 ASC treatment revealed a significant decrease of Laverty's score at 16 weeks compared to the OA group (P < 0.01), which instead gave evidence of a series of changes, including chondrocyte and proteoglycan loss, fibrillation and delamination processes. A progression of the pathology, was also noticed in the 4% RSA group at 16 and 24 weeks compared to OA (P < 0.01). In general, ASC administration determined a decrease of Laverty's scores compared to 4% RSA (P < 0.01) at both experimental times.


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 medial femoral condyle in OA, 4% RSA and ASC-treated groups. (A) Safranin-O/Fast Green staining of representative specimens. Black arrows, fibrillation and delamination processes. Red arrows, Erosion processes. Scale bars = 1,000 μm. (B) Laverty's score. Data are reported in terms of 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 5: Histological evaluation of medial femoral condyle in OA, 4% RSA and ASC-treated groups. (A) Safranin-O/Fast Green staining of representative specimens. Black arrows, fibrillation and delamination processes. Red arrows, Erosion processes. Scale bars = 1,000 μm. (B) Laverty's score. Data are reported in terms of 95% confidence intervals. Statistical values of at least P < 0.01 were observed in all the comparisons.
Mentions: A glossy, white cartilage with no degenerative noticeable macroscopic evidence was observed in the ASCS-treated groups at both experimental times. Cartilage softening and fibrillation were instead observed in the OA and 4% RSA groups particularly in the medial regions (data not shown). Histo-morphometric analyses provided further information on the status of the structure of cartilage tissue. Among the pathological changes recorded during OA, an increase of FI was observed in OA group compared to 4% RSA at both 16 and 24 weeks (P < 0.01). A significant reduction of FI was noticed in both ASCs treated groups at 16 weeks compared to 4% RSA at both experimental times (P < 0,01), indicating a protective role of ASCs in reducing fibrillation processes (Figure 4A). The intra-articular delivery of 2 × 106 ASCs revealed an increase of CT values respect the OA group and 4% RSA at 16 and 24 weeks (P < 0.01) (Figure 4B). Based on visual assessment of the histological staining, there were significant, overall effects of ASCs in the healing of cartilaginous tissue which displayed some hyaline features with a smooth surface, a regular cellular arrangement and a high proteoglycan content leading to a functional cartilage tissue (Figure 5A, B). In particular, 2 × 106 ASC treatment revealed a significant decrease of Laverty's score at 16 weeks compared to the OA group (P < 0.01), which instead gave evidence of a series of changes, including chondrocyte and proteoglycan loss, fibrillation and delamination processes. A progression of the pathology, was also noticed in the 4% RSA group at 16 and 24 weeks compared to OA (P < 0.01). In general, ASC administration determined a decrease of Laverty's scores compared to 4% RSA (P < 0.01) at both experimental times.

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