Abstract
Multiple therapies have been developed to slow down the progression of knee osteoarthritis
(OA), with the aim of avoiding or delaying TKA. One such potential method is cell-mediated
gene therapy, which utilizes allogeneic human chondrocytes modified to express transforming
growth factor-β1. Using magnetic resonance imaging (MRI), we evaluated patients who
underwent treatment with this injection in a Phase II study and assessed structural
changes in: (1) bone marrow edema lesions, (2) cartilage defect depth and surface
area, (3) articular bone surface and osteophytes, and (4) meniscus structure and signal,
as well as changes in (5) joint fluid, (6) periarticular inflammation, and (7) synovial
inflammation. Twenty-seven patients (6 men and 21 women) who had late-stage OA were
randomized 1:1 to receive a 3:1 mixture of nontransduced chondrocytes and genetically
engineered chondrocytes, at doses of 6 × 106 cells (group 1) or 1.8 × 107 cells (group 2). MRI was performed at baseline (preinjection), and at 6 and 12 months
postinjection. The whole-organ MRI score system was used to assess the aforementioned
changes. Treatment was considered to be successful if patients experienced an improvement
in or no change in their scores, indicating that the disease had not progressed. All
patients in both cohorts individually demonstrated an improvement or no change in
one or more of the assessment parameters. At 6 months, the low-dose cohort demonstrated
worsening in mean scores in one parameter (bone surface and osteophytes), while the
high-dose cohort demonstrated no worsening in mean scores. At 12 months, the low-dose
cohort had worsening in the mean score in a subset of one parameter (cartilage signal
intensity), and the high-dose cohort demonstrated worsening in mean scores in two
parameters (bone surface osteophytes and periarticular inflammation). This is the
first study to evaluate MRI changes in patients treated with this injection. These
findings provide an impetus for further research on this topic, as well as a starting
point for Phase III testing.
Keywords
MRI - cartilage regeneration - osteoarthritis - TissueGene-C
