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N. Nakamura, H. Yoshikawa, K. Shino
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chondral lesions of the knee. We reviewed all
the clinical trials of cell-based therapy for
symptomatic chondral lesions of the knee
including randomized controlled trials,
prospective comparative studies, systematic
reviews and case series studies.
Three review authors selected studies for
inclusion independently. Records retrieved by
the initial search were scanned by review
authors to exclude obviously irrelevant studies.
Full text articles were retrieved and reviewed
independently by the authors. Differences of
opinion were resolved by discussion among the
authors.
Data from the studies were evaluated
independently using the rating system of the
Journal of Bone and Joint Surgery
“Levels of
Evidence for Primary Research” for therapeutic
studies as published in the Arthroscopy Journal
InstructionsforAuthors.Thescoring,specifically
Levels I and II, was supported by the methods
for methodological quality assessment by the
Cochrane Database Systematic Review [6] and
Schulz
et al.
[7]. All differences of opinion
between the authorswere resolved by discussion.
Original therapeutic studies of Levels I and II
and recent important systematic reviews (Levels
I-III) were reviewed in this study.
Analyses
Statistical analyses were not undertaken due to
clinical and methodological heterogeneity in
the available studies and reviewed studies were
described individually.
Results
Twelve randomized controlled trials (RCTs)
and three prospective comparative studies,
comparing ACI with any other type of cartilage
repair surgery, were identified. One prospective
comparative study on the outcome of ACI
according to the sports activity level and one
prospective comparative study on the outcome
ofACIaccordingtotheacceleratedrehabilitation
were identified.
Based on these methodological quality
assessments, we evaluated five RCTs as Level I
and the other RCTs as Level II. In addition, five
prospective comparative studies were classified
as Level II. We summarize the Level I and II
prospective comparative studies in Table.
Discussion
Since year 1994, over 80 studies on cell-based
cartilage repair have been published, while
majority of the studies are Level IV study
which have no control group. Most of the Level
IV studies reviewed in here reported promising
results, however, there appear lot of room to
introduce bias and may not be appropriate to
draw any specific conclusion to evaluate the
feasibility of the treatment procedures to
cartilage repair. Several treatment options are
currently performed for chondral lesions
including stimulation of a repair process by the
penetration of the subchondral bone such as
microfracture and drilling, and replacement of
the damaged articular surface by osteochondral
graft [1, 2]. Since cell-based therapy is generally
time and cost-consuming procedures with
potential risk accompanying cell culture, it
should have significant advantage over such
conventional treatment options in clinical
application. Therefore, comparative studies are
required. However, we could identify only
15 prospective comparative studies including
12 RCTs. All RCTs dealt withACI, and three of
them compared ACI with osteochondral
grafting procedures. While these 3 studies had
substantial flaws which could introduce bias,
we over all found no difference between the
cell-based studies and osteochondral grafting.
Only one study [9] reported statistically
significant results that ACI is superior based on
ICRS arthroscopic evaluation. However, only
30% of the total number randomized received
arthroscopy. This study also showed that ACI
gave better clinical outcomes than mosaicplasty
but this was only observed at medial femoral
condylar defects and appears to have been
based on an unplanned subgroup analysis of
participants. When taking into account all
participants, significant differences might not
be clearly noted.