SMW Supplementum 193 - Swiss Medical Weekly

47 S SWiSS Med Wkly 2012;142(Suppl 193) · www.smw.ch Posters
P44
Tissue engineered nasal cartilage for the regeneration
of articular cartilage in goats
Marcus Mumme1 , Karoliina Pelttari2 , Sinan Gueven2 , Brigitte Von
Rechenberg3 , Marcel Jakob1 , Ivan Martin2 , Andrea Barbero2 1 2 Clinic for Traumatology, University Hospital Basel; Department of
Biomedicine, University Hospital Basel; 3Musculoskeletal Research
Unit, Equine Hospital, Vetsuisse Faculty ZH, Zurich
Introduction: As compared to articular chondrocytes (AC), nasal
septum chondrocytes (NC) proliferate faster and have a higher and
more reproducible capacity to generate hyaline-like cartilaginous
tissues. Moreover, the use of NC would allow reducing the morbidity
associated with the harvesting of cartilage biopsy from the patient. The
objective of the present study was to demonstrate safety and feasibility
in the use of tissue engineered cartilage graft based on autologous
nasal chondrocytes for the repair of articular defect in goats.
Methods: Isolated autologous NC and AC from 6 goats were
expanded and GFP-labelledbefore seeding 4x104 cells/cm2 on atype
I/III collagenmembrane (Chondro-Gide ® , Geistlich). After 2 weeks
of chondrogenic differentiation 2 NC- and 2 AC-based grafts were
implanted into chondral defects (6 mm diameter) of the same posterior
stifle joint. Repair tissue was harvested after 3 or 6 months and the
decalcified samples evaluated according to O’Driscoll. Furthermore,
samples from the surrounding fat pad, ligament, synovium, tendon
and patellar cartilage were harvested and isolated cells tested for
GFP-positivity after expansion using FACS.
Results: No complications or signs of inflammation occurred in any
of the animals. GFP-positive cells were detectable in the repair tissue,
indicating the contribution of the implanted cells to the newly formed
cartilage. The O’Driscoll score of 8.6 and 7.6 after 3 months increased
to 14.1 and 12.4 after 6 months for nasal and articular grafts,
respectively. Surrounding tissues showed no or very low (fat pad
0–0.36%) migration of the grafted cells.
Conclusion: Our results demonstrate the use of NC as safe and
feasible for tissue engineering approaches in articular cartilage repair.
The repair tissue-quality generated by NC-grafts was demonstrated to
be at least comparable to that of AC-grafts, thus opening the way for
clinical test of a novel therapeutic strategy.
Acknowledgements: This work was financed by SNF grant
310030_126965/1.
P45
Evaluation of positron emission tomography
in preclinical models of osteosarcoma
Carmen Campanile1 , Matthias Arlt1 , Michael Honer2 ,
Stefanie Krämer2 , Simon Ametamey2 , Roger Schibli2 ,
Walter Born1 , Bruno Fuchs1 1 2 Uniklinik Balgrist; ETH Hönggerberg
Introduction: Osteosarcoma (OS) is the most common malignant
bone tumor in children and adolescents characterized by the
production of immature bone, osteoid. In normal bone, the resorbtion
by osteoclasts is linked to bone formation. In OS, osteolytic and
osteoblastic phenotypes, as a result of imbalanced bone resorption
and formation, are distinguished radio- and histologically. The different
phenotypes, associated with differences in tumor proliferation and
hypoxia, determine at least in part the response to chemotherapy and,
consequently, the patient’s outcome. Novel minimally-invasive
diagnostic tools are needed for future more patient-tailored treatment
depending on more precisely defined tumor phenotypes. Here,
Positrion Emission Tomography (PET) with 18F-FDG, indicating
glucose metabolism, 18F-Fluoride, indicating bone remodelling and
18F-FMISO indicating hypoxia, is used in 3 different mouse models
with well-defined phenotypes, reflecting OS heterogeneity, to evaluate
the respective predictive power of the 3 PET tracers in OS diagnostics.
Methods: 2 human (143B, osteolytic; and SaOS-2, osteoblastic) and
1 mouse OS cell line (LM8-osteoblastic) were intratibially injected in
SCID immunosuppressed and C3H immunocompetent mice,
respectively. Intratibial primary tumor development was monitored by
X-ray. PET was performed at the Animal Imaging Center at ETH-
Hönggerberg 3 weeks after tumor cell injection in the 143B and LM8
models and between 2 and 5 months after injection of human SaOS-2
cells in SCID mice. Tracer uptake in the tumor leg was quantified with
p-mod software and compared to the control leg.
Results: In the 143B cell line, a significantly higher uptake of FDG and
FMISO is observed in the tumor compared to the control leg, but there
is no difference in Fluoride uptake which is consistent with the
histological results. The SaOS-2 cell derived tumors, on the other
hand, display high uptake of FDG, FMISO and Fluoride, reflecting a
proliferative and hypoxic osteoblastic phenotype. LM8 mouse OS cell
derived tumors show a high tumor selective accumulation of FDG, but
only moderate uptake of FMISO and Fluoride consistent with low
osteoblastic activity and hypoxia.
Conclusions: FDG, FMISO and Fluoride proofed to be predictive in
the 3 intratibial OS mouse models with well characterized phenotypes
and therefore suitable for primary tumor monitoring in pre-clinical
studies investigating novel phenotype- and histotype-specific
treatment modalities.
P46
Gemcitabine significantly inhibits primary tumor growth
and metastasis of lacZ-tagged and untagged LM8
osteosarcoma cells in syngeneic C3H mice
Matthias Arlt, Ingo Banke, Denise Walters, Patrick Steinmann,
Kersten Berndt, Walter Born, Bruno Fuchs
Uniklinik Balgrist
Introduction: Gemcitabine, an analog of cytosine arabinoside, is a
standard chemotherapeutic that interferes with DNA synthesis. It
shows good antineoplastic activity against a variety of human cancers.
So far, gemcitabine has not been clinically tested in osteosarcoma
(OS), the most frequent primary malignant bone tumor. In the present
study, we pre-clinically investigated the potential of gemcitabine to
inhibit primary tumor growth and metastasis in the established murine
LM8 OS model.
Methods: C3H mice were subcutaneously inoculated with 1x107
lacZ-tagged or untagged LM8 cells and then treated intraperitoneally
with 150 mg/kg gemcitabine or vehicle control on day 7, 14 and 21.
On day 26, all mice were sacrificed and lungs and livers removed.
For the LacZ-tagged LM8 cells, indigo-blue OS metastases on the
organ surfaces were counted after X-Gal staining. For comparison,
metastases were counted in H&E stained paraffin sections of lung and
liver tissue of mice injected with lacZ-tagged LM8 as well as of those
inoculated with the untagged LM8 cells.
Results: Gemcitabine strongly inhibited primary tumor growth in both
LM8- and LM8-lacZ-inoculated mice resulting in significantly (P