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The Journal of Bone and Joint Surgery, Vol 76, Issue 4 579-592, Copyright © 1994 by Journal of Bone and Joint Surgery, Inc
Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage
S Wakitani, T Goto, SJ Pineda, RG Young, JM Mansour, AI Caplan and VM Goldberg
Department of Orthopaedics, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Ohio 44106.
Osteochondral progenitor cells were used to repair large, full-thickness
defects of the articular cartilage that had been created in the knees of
rabbits. Adherent cells from bone marrow, or cells from the periosteum that
had been liberated from connective tissue by collagenase digestion, were
grown in culture, dispersed in a type-I collagen gel, and transplanted into
a large (three-by-six-millimeter), full-thickness (three-millimeter) defect
in the weight-bearing surface of the medial femoral condyle. The
contralateral knee served as a control: either the defect in that knee was
left empty or a cell-free collagen gel was implanted. The periosteal and
the bone-marrow-derived cells showed similar patterns of differentiation
into articular cartilage and subchondral bone. Specimens of reparative
tissue were analyzed with use of a semiquantitative histological grading
system and by mechanical testing with employment of a porous indenter to
measure the compliance of the tissue at intervals until twenty-four weeks
after the operation. There was no apparent difference between the results
obtained with the cells from the bone marrow and those from the periosteum.
As early as two weeks after transplantation, the autologous osteochondral
progenitor cells had uniformly differentiated into chondrocytes throughout
the defects. This repair cartilage was subsequently replaced with bone in a
proximal-to-distal direction, until, at twenty-four weeks after
transplantation, the subchondral bone was completely repaired, without loss
of overlying articular cartilage. The mechanical testing data were a useful
index of the quality of the long-term repair. Twenty-four weeks after
transplantation, the reparative tissue of both the bone-marrow and the
periosteal cells was stiffer and less compliant than the tissue derived
from the empty defects but less stiff and more compliant than normal
cartilage. Clinical Relevance: The current modalities for the repair of
defects of the articular cartilage have many disadvantages. The
transplantation of progenitor cells that will form cartilage and bone
offers a possible alternative to these methods. As demonstrated in this
report, autologous, bone-marrow-derived, osteochondral progenitor cells can
be isolated and grown in vitro without the loss of their capacity to
differentiate into cartilage or bone. Sufficient autologous cells can be
generated to initiate the repair of articular cartilage and the reformation
of subchondral bone. The repair tissues appear to undergo the same
developmental transitions that originally led to the formation of articular
tissue in the embryo.(ABSTRACT TRUNCATED AT 400 WORDS)
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