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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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Immunohistochemical analysis for MMP-1 and TNF-α in cartilage. Photomicrographs of representative specimens evaluated for MMP-1 (A) and TNF-α (B) in medial femoral condyle of OA, 4% RSA and ASC-treated groups. Data are reported as mean ± SD. Scale bars = 100 μm. Statistical values of at least P < 0.01 were observed in all the comparisons.
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Figure 9: Immunohistochemical analysis for MMP-1 and TNF-α in cartilage. Photomicrographs of representative specimens evaluated for MMP-1 (A) and TNF-α (B) in medial femoral condyle of OA, 4% RSA and ASC-treated groups. Data are reported as mean ± SD. Scale bars = 100 μm. Statistical values of at least P < 0.01 were observed in all the comparisons.

Mentions: Since the degradation of cartilage matrix represents a key event in the development of OA, we decided to test the effect of ASC treatment on catabolic and inflammatory molecules involved in the OA onset. We first investigated the typical hyaline marker, collagen type II, detecting a decrease of this molecule in the 4% RSA at 24 weeks in respect to the OA group (P < 0.01). ASC treatment gave evidence of a chondro-protective effect, promoting the expression of a great amount of type II collagen in the cartilage tissue in respect to the OA and 4% RSA groups (P < 0.01). In particular, high percentages of positive areas in the 2 × 106 and 6 × 106 ASC-treated groups at 16 and 24 weeks were detected. A reduced expression of collagen type II was noticed in 4% RSA, 2 × 106 and 6 × 106 ASCs at 24 weeks compared to 16 weeks (P < 0.01) (Figure 8A). Collagen type I, a fibro-cartilaginous marker, reported an intense positivity at cellular level in the OA group, particularly at the superficial level in cartilage matrix. The 4% RSA group displayed an increased expression of type I collagen particularly at 24 weeks compared to the OA group (P < 0.01). A reduction of collagen type I was detected in the ASC-treated groups at short- and long-term follow-ups with respect to the 4% RSA group (P < 0.01) (Figure 8B). A moderate expression of MMP-1 was noticed in the OA group, particularly in the superficial layer of cartilage. An increased expression of this protein was observed in the 4% RSA group. By contrast, ASC-treated groups showed a low expression for MMP-1 compared to the OA group and 4% RSA group at 16 and 24 weeks (P < 0.01) (Figure 9A). The OA group displayed a moderate expression of TNF-α which increased progressively in 4% RSA at 16 and 24 weeks (P < 0.01). A reduction of TNF- α expression was detected in both the ASC-treated groups at 16 weeks and 24 weeks with respect to the OA and 4% RSA groups (P < 0.01) (Figure 9B).


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)

Immunohistochemical analysis for MMP-1 and TNF-α in cartilage. Photomicrographs of representative specimens evaluated for MMP-1 (A) and TNF-α (B) in medial femoral condyle of OA, 4% RSA and ASC-treated groups. Data are reported as mean ± SD. Scale bars = 100 μm. 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 9: Immunohistochemical analysis for MMP-1 and TNF-α in cartilage. Photomicrographs of representative specimens evaluated for MMP-1 (A) and TNF-α (B) in medial femoral condyle of OA, 4% RSA and ASC-treated groups. Data are reported as mean ± SD. Scale bars = 100 μm. Statistical values of at least P < 0.01 were observed in all the comparisons.
Mentions: Since the degradation of cartilage matrix represents a key event in the development of OA, we decided to test the effect of ASC treatment on catabolic and inflammatory molecules involved in the OA onset. We first investigated the typical hyaline marker, collagen type II, detecting a decrease of this molecule in the 4% RSA at 24 weeks in respect to the OA group (P < 0.01). ASC treatment gave evidence of a chondro-protective effect, promoting the expression of a great amount of type II collagen in the cartilage tissue in respect to the OA and 4% RSA groups (P < 0.01). In particular, high percentages of positive areas in the 2 × 106 and 6 × 106 ASC-treated groups at 16 and 24 weeks were detected. A reduced expression of collagen type II was noticed in 4% RSA, 2 × 106 and 6 × 106 ASCs at 24 weeks compared to 16 weeks (P < 0.01) (Figure 8A). Collagen type I, a fibro-cartilaginous marker, reported an intense positivity at cellular level in the OA group, particularly at the superficial level in cartilage matrix. The 4% RSA group displayed an increased expression of type I collagen particularly at 24 weeks compared to the OA group (P < 0.01). A reduction of collagen type I was detected in the ASC-treated groups at short- and long-term follow-ups with respect to the 4% RSA group (P < 0.01) (Figure 8B). A moderate expression of MMP-1 was noticed in the OA group, particularly in the superficial layer of cartilage. An increased expression of this protein was observed in the 4% RSA group. By contrast, ASC-treated groups showed a low expression for MMP-1 compared to the OA group and 4% RSA group at 16 and 24 weeks (P < 0.01) (Figure 9A). The OA group displayed a moderate expression of TNF-α which increased progressively in 4% RSA at 16 and 24 weeks (P < 0.01). A reduction of TNF- α expression was detected in both the ASC-treated groups at 16 weeks and 24 weeks with respect to the OA and 4% RSA groups (P < 0.01) (Figure 9B).

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