Autologous chondrocyte implantation for cartilage repair: monitoring its success by magnetic resonance imaging and histology

Abstract

Autologous chondrocyte implantation is being used increasingly for the treatment of cartilage defects. In spite of this, there has been a paucity of objective, standardised assessment of the outcome and quality of repair tissue formed. We have investigated patients treated with autologous chondrocyte implantation (ACI), some in conjunction with mosaicplasty, and developed objective, semiquantitative scoring schemes to monitor the repair tissue using MRI and histology. Results indicate repair tissue to be on average 2.5 mm thick. It was of varying morphology ranging from predominantly hyaline in 22% of biopsy specimens, mixed in 48%, through to predominantly fibrocartilage, in 30%, apparently improving with increasing time postgraft. Repair tissue was well integrated with the host tissue in all aspects viewed. MRI scans provide a useful assessment of properties of the whole graft area and adjacent tissue and is a noninvasive technique for long-term follow-up. It correlated with histology (P = 0.02) in patients treated with ACI alone.

Figure 1

Integration between repaired cartilage and underlying bone, seen particularly clearly when a section stained with H&E (a) is viewed with polarised light (b) (sample 4). (c) An oblique section from the surface zone (S) through hyaline cartilage of the mosaic plug (H) to fibrocartilage matrix (F), immunostained for type II collagen. (d) H&E-stained higher power of the junctional zone (B, underlying bone) and (e) the same section viewed with polarised light. Full integration can be seen across this zone in sections immunostained for (f) type I and (g) type II collagen (sample 2). H&E = haematoxylin and eosin.

Figure 2

Use of MRI after ACI in joints. (a) The status of the whole knee (sample 7, sagittal T₁-weighted spin echo, TR = 722, TE = 20, field of view = 20 cm). (b) Cartilage surface congruity and cartilage overgrowth (arrowhead, sample 3) and (c) cartilage filling a subchondral defect (arrowhead, sample 7) can be identified on 3D T₁-weighted images with fat suppression. Similarly, the images can demonstrate changes in the bone, whether uneven bone profile (b) (dotted arrow), cysts in the underlying subchondral bone (d,e) (arrowheads), or artefacts (b) (asterisk). MRI is particularly suitable for longitudinal study of grafts such as can be seen in (d) and (e), which were taken at, respectively, 6 and 30 months after ACI treatment (sample 22, 3D dual excitation in the steady state with fat suppression). 3D = three-dimensional; ACI = autologous chondrocyte implantation; MRI = magnetic resonance imaging; TE = echo time; TR = repetition time.

Figure 3

Immunohistochemical study of type II collagen after autologous chondrocyte implantation. Type II collagen is seen throughout most hyaline-like repair tissue (c), as identified on an adjacent section stained with H&E (a) and viewed with polarised light (b), showing zonal matrix organisation similar to that seen in normal adult articular cartilage in the surface (S), mid (M), and deep (D) zones (sample 22). In (c), note the lack of staining for type II collagen both at the surface (N) and in the bone (B). Samples with a mixed morphology (d-f) (sample 16) and some with a fibrocartilage morphology were mostly stained positively for type II collagen also, whereas a few fibrocartilagenous biopsy specimens (g) (sample 14) were negative for type II collagen (h). H&E = haematoxylin and eosin.

Figure 4

Immunostaining for type I collagen after autologous chondrocyte implantation. Type I collagen was restricted primarily to the upper region (arrow) and bone (B) in hyaline-like cartilage (a) (sample 22) but was more widespread where the morphology was mixed (b) (sample 16) or particularly when it was fibrocartilaginous (c) (sample 14).

Figure 5

Immunostaining for type X collagen after autologous chondrocyte implantation. Staining was typically seen around the cells in the deep zone (arrows) and calcified cartilage (sample 16).

Figure 6

Immunostaining for type III collagen after autologous chondrocyte implantation. The distribution of type III collagen was predominantly pericellular in hyaline-like cartilage (a) (sample 22) and (b) (H) (sample 2), whereas in specimens with a more fibrocartilaginous morphology (b) (F) (sample 2) and (c) (sample 15), it was predominantly homogeneous throughout the extracellular matrix.

Figure 7

Immunostaining for glycosaminoglycan epitopes after autologous chondrocyte implantation. Staining was stronger for chondroitin-4-sulfate (2-B-6) (a), chondroitin-6-sulfate (3-B-3) (b), and keratan sulfate (5-D-4) (d) than for the abnormally sulfated chondroitin-6-sulfate epitopes, 3-B-3(-) (c) (sample 6). C-4-S, chondroitin-4-sulfate; C-6-S, chondroitin-6-sulfate; K-S, keratan sulfate.

Figure 8

Typical staining and immunostaining patterns for control cartilage. Haematoxylin and eosin (a), type II collagen (b), type I collagen in the surface zone (c) and the deep zone (d) and type X collagen (e). B, bone; CC, calcified cartilage.