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International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials.

Hoemann C, Kandel R, Roberts S, Saris DB, Creemers L, Mainil-Varlet P, Méthot S, Hollander AP, Buschmann MD - Cartilage (2011)

Bottom Line: Methods were compiled from a literature review, and illustrative data were added.In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points.Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, Institute of Biomedical Engineering, École Polytechnique, Montréal, Quebec, Canada.

ABSTRACT
Cartilage repair strategies aim to resurface a lesion with osteochondral tissue resembling native cartilage, but a variety of repair tissues are usually observed. Histology is an important structural outcome that could serve as an interim measure of efficacy in randomized controlled clinical studies. The purpose of this article is to propose guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies. Methods were compiled from a literature review, and illustrative data were added. In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points. In human clinical therapy, treatments are applied to developed lesions, and biopsies are obtained, usually from a subset of patients, at a specific time point. In striving to standardize evaluation of structural endpoints in cartilage repair studies, 5 variables should be controlled: 1) location of biopsy/sample section, 2) timing of biopsy/sample recovery, 3) histoprocessing, 4) staining, and 5) blinded evaluation with a proper control group. Histological scores, quantitative histomorphometry of repair tissue thickness, percentage of tissue staining for collagens and glycosaminoglycan, polarized light microscopy for collagen fibril organization, and subchondral bone integration/structure are all relevant outcome measures that can be collected and used to assess the efficacy of novel therapeutics. Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies. Currently, there are no suitable substitutes for histology in evaluating repair tissue quality and cartilaginous character.

No MeSH data available.


Related in: MedlinePlus

Different features of the osteochondral junction in normal and repair cartilage are revealed by hematoxylin and eosin (H & E) (A, C, E, G) and Safranin O/fast green/iron hematoxylin (SafO) (B, D, F, H). In normal human cartilage (A and B, adult hip surgical waste, femoral neck fracture), H&E clearly stains the tidemark (A, white arrows), while SafO readily discriminates cartilage from fast green–stained bone (below the black arrows, B). For heterogeneous human repair cartilage (C and D, biopsy taken 1 year postmicrofracture71,121), H&E is better for determining the cartilage-bone boundary (black arrows, C) and abnormal mineralization (dashed circle), while SafO discriminates fibrocartilage from fast green–stained fibrous repair and bone (D). In hyaline cartilage repair elicited in a sheep model (E-H, 6 months posttreatment43), the tidemark is beginning to form (white arrows, 10x magnification for E and F, 40x magnification for G and H). White arrows = tidemark; black arrows = cartilage-bone interface; AC = articular cartilage; cc = calcified cartilage; FC = fibrocartilage; HC = hyaline cartilage; b = bone.
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fig1-1947603510397535: Different features of the osteochondral junction in normal and repair cartilage are revealed by hematoxylin and eosin (H & E) (A, C, E, G) and Safranin O/fast green/iron hematoxylin (SafO) (B, D, F, H). In normal human cartilage (A and B, adult hip surgical waste, femoral neck fracture), H&E clearly stains the tidemark (A, white arrows), while SafO readily discriminates cartilage from fast green–stained bone (below the black arrows, B). For heterogeneous human repair cartilage (C and D, biopsy taken 1 year postmicrofracture71,121), H&E is better for determining the cartilage-bone boundary (black arrows, C) and abnormal mineralization (dashed circle), while SafO discriminates fibrocartilage from fast green–stained fibrous repair and bone (D). In hyaline cartilage repair elicited in a sheep model (E-H, 6 months posttreatment43), the tidemark is beginning to form (white arrows, 10x magnification for E and F, 40x magnification for G and H). White arrows = tidemark; black arrows = cartilage-bone interface; AC = articular cartilage; cc = calcified cartilage; FC = fibrocartilage; HC = hyaline cartilage; b = bone.

Mentions: Articular cartilage is structurally organized into 3 distinct zones (Table 1).15 The superficial zone is a relatively thin layer with horizontally oriented collagen bundles and flattened chondrocytes. The midzone is thicker and contains rounded chondrocytes and collagen bundles with heterogeneous orientation. The deep zone usually represents over half of the articular cartilage thickness in skeletally mature large animals and humans.21,22 The deep zone contains larger chondrocytes and collagen fibers oriented perpendicular to the surface, which are also anchored into the calcified cartilage below. The tidemark is a mineralized cement line demarcating the noncalcified and calcified cartilage interface23,24 (Figs. 1A and 1B). In the calcified cartilage layer, chondrocytes are quiescent, fewer in number, produce collagen type X, and express alkaline phosphatase.24-26 Healthy subchondral bone is also important for maintenance of the articular cartilage layer.27-31 In preclinical and clinical studies for cartilage repair, histology can be used as one of the structural outcome measures since it can provide information on the type of matrix and cellular components present and their relative organization. By utilizing other more complex techniques, such as immunohistochemistry or in situ hybridization, individual or particular cellular processes can be identified and localized.


International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials.

Hoemann C, Kandel R, Roberts S, Saris DB, Creemers L, Mainil-Varlet P, Méthot S, Hollander AP, Buschmann MD - Cartilage (2011)

Different features of the osteochondral junction in normal and repair cartilage are revealed by hematoxylin and eosin (H & E) (A, C, E, G) and Safranin O/fast green/iron hematoxylin (SafO) (B, D, F, H). In normal human cartilage (A and B, adult hip surgical waste, femoral neck fracture), H&E clearly stains the tidemark (A, white arrows), while SafO readily discriminates cartilage from fast green–stained bone (below the black arrows, B). For heterogeneous human repair cartilage (C and D, biopsy taken 1 year postmicrofracture71,121), H&E is better for determining the cartilage-bone boundary (black arrows, C) and abnormal mineralization (dashed circle), while SafO discriminates fibrocartilage from fast green–stained fibrous repair and bone (D). In hyaline cartilage repair elicited in a sheep model (E-H, 6 months posttreatment43), the tidemark is beginning to form (white arrows, 10x magnification for E and F, 40x magnification for G and H). White arrows = tidemark; black arrows = cartilage-bone interface; AC = articular cartilage; cc = calcified cartilage; FC = fibrocartilage; HC = hyaline cartilage; b = bone.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4300784&req=5

fig1-1947603510397535: Different features of the osteochondral junction in normal and repair cartilage are revealed by hematoxylin and eosin (H & E) (A, C, E, G) and Safranin O/fast green/iron hematoxylin (SafO) (B, D, F, H). In normal human cartilage (A and B, adult hip surgical waste, femoral neck fracture), H&E clearly stains the tidemark (A, white arrows), while SafO readily discriminates cartilage from fast green–stained bone (below the black arrows, B). For heterogeneous human repair cartilage (C and D, biopsy taken 1 year postmicrofracture71,121), H&E is better for determining the cartilage-bone boundary (black arrows, C) and abnormal mineralization (dashed circle), while SafO discriminates fibrocartilage from fast green–stained fibrous repair and bone (D). In hyaline cartilage repair elicited in a sheep model (E-H, 6 months posttreatment43), the tidemark is beginning to form (white arrows, 10x magnification for E and F, 40x magnification for G and H). White arrows = tidemark; black arrows = cartilage-bone interface; AC = articular cartilage; cc = calcified cartilage; FC = fibrocartilage; HC = hyaline cartilage; b = bone.
Mentions: Articular cartilage is structurally organized into 3 distinct zones (Table 1).15 The superficial zone is a relatively thin layer with horizontally oriented collagen bundles and flattened chondrocytes. The midzone is thicker and contains rounded chondrocytes and collagen bundles with heterogeneous orientation. The deep zone usually represents over half of the articular cartilage thickness in skeletally mature large animals and humans.21,22 The deep zone contains larger chondrocytes and collagen fibers oriented perpendicular to the surface, which are also anchored into the calcified cartilage below. The tidemark is a mineralized cement line demarcating the noncalcified and calcified cartilage interface23,24 (Figs. 1A and 1B). In the calcified cartilage layer, chondrocytes are quiescent, fewer in number, produce collagen type X, and express alkaline phosphatase.24-26 Healthy subchondral bone is also important for maintenance of the articular cartilage layer.27-31 In preclinical and clinical studies for cartilage repair, histology can be used as one of the structural outcome measures since it can provide information on the type of matrix and cellular components present and their relative organization. By utilizing other more complex techniques, such as immunohistochemistry or in situ hybridization, individual or particular cellular processes can be identified and localized.

Bottom Line: Methods were compiled from a literature review, and illustrative data were added.In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points.Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, Institute of Biomedical Engineering, École Polytechnique, Montréal, Quebec, Canada.

ABSTRACT
Cartilage repair strategies aim to resurface a lesion with osteochondral tissue resembling native cartilage, but a variety of repair tissues are usually observed. Histology is an important structural outcome that could serve as an interim measure of efficacy in randomized controlled clinical studies. The purpose of this article is to propose guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies. Methods were compiled from a literature review, and illustrative data were added. In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points. In human clinical therapy, treatments are applied to developed lesions, and biopsies are obtained, usually from a subset of patients, at a specific time point. In striving to standardize evaluation of structural endpoints in cartilage repair studies, 5 variables should be controlled: 1) location of biopsy/sample section, 2) timing of biopsy/sample recovery, 3) histoprocessing, 4) staining, and 5) blinded evaluation with a proper control group. Histological scores, quantitative histomorphometry of repair tissue thickness, percentage of tissue staining for collagens and glycosaminoglycan, polarized light microscopy for collagen fibril organization, and subchondral bone integration/structure are all relevant outcome measures that can be collected and used to assess the efficacy of novel therapeutics. Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies. Currently, there are no suitable substitutes for histology in evaluating repair tissue quality and cartilaginous character.

No MeSH data available.


Related in: MedlinePlus