Pregledni rad
Clinical potential and challenges of using genetically modified cells for articular cartilage repair
Henning Madry
orcid.org/0000-0002-8612-4842
; Experimental Orthopaedics and Osteoarthritis Research, Saarland University Medical Center and Saarland University, Homburg/Saar Germany
Magali Cucchiarini
; Experimental Orthopaedics and Osteoarthritis Research, Saarland University Medical Center and Saarland University, Homburg/Saar Germany
Sažetak
Articular cartilage defects do not regenerate. Transplantation
of autologous articular chondrocytes, which is clinically
being performed since several decades, laid the foundation
for the transplantation of genetically modified cells,
which may serve the dual role of providing a cell population
capable of chondrogenesis and an additional stimulus
for targeted articular cartilage repair. Experimental data
generated so far have shown that genetically modified articular
chondrocytes and mesenchymal stem cells (MSC)
allow for sustained transgene expression when transplanted
into articular cartilage defects in vivo. Overexpression of
therapeutic factors enhances the structural features of the
cartilaginous repair tissue. Combined overexpression of
genes with complementary mechanisms of action is also
feasible, holding promises for further enhancement of articular
cartilage repair. Significant benefits have been also
observed in preclinical animal models that are, in principle,
more appropriate to the clinical situation. Finally, there
is convincing proof of concept based on a phase I clinical
gene therapy study in which transduced fibroblasts were
injected into the metacarpophalangeal joints of patients
without adverse events. To realize the full clinical potential
of this approach, issues that need to be addressed include
its safety, the choice of the ideal gene vector system
allowing for a long-term transgene expression, the identification
of the optimal therapeutic gene(s), the transplantation
without or with supportive biomaterials, and
the establishment of the optimal dose of modified cells.
As safe techniques for generating genetically engineered
articular chondrocytes and MSCs are available, they may
eventually represent new avenues for improved cell-based
therapies for articular cartilage repair. This, in turn, may provide
an important step toward the unanswered question
of articular cartilage regeneration.
Ključne riječi
Hrčak ID:
71436
URI
Datum izdavanja:
15.6.2011.
Posjeta: 1.211 *