ÖGMKG - und Gesichtschirurgie

Gassner, Robert
The Effect of Aging of Human Mesenchymal Stem Cells Treating
Craniofacial Anomalies (Se01-02)
Robert Gassner1, Frank Kloss1, Oliver Hächl1, Tarkan Tuli1, Michael Rasse1, Christine Fehrer2,
Regina Brunauer2, Gerhard Laschober2, Hermann Unterluggauer2, Stephan Reitinger2, Günter
Lepperdinger2 (Robert.Gassner@uibk.ac.at)
1: Dept. of Cranio-Maxillofacial Surgery, University Hospital of Innsbruck, Innsbruck, Austria; 2:
Austrian Academy of Sciences, Institute for Biomedical Aging Research, Innsbruck, Austria
Corrective surgery of craniofacial anomalies often requires bone harvesting and transplantation.
The aim of this study was to assess biopsies from iliac crests of differently aged human donors
for the presence of mesenchymal stem cells (MSC). MSC are self-renewing entities while
generating multipotential progeny. Therefore, this class of cells is of paramount importance
for bone repair and bone healing. We studied MSC aging and provide evidence that besides
the individual age of the cell, stem and progenitor cell functions are influenced by the cellular
environment.
Biopsies from iliac crests were digested to collect MSC. Primary colony forming units, growth
rates during long-term culture, senescent marker expression, in vitro differentiation capacity
into osteogenic and adipogenic lineage as well as expression profiles employing whole genome
arrays were determined using standard procedures.
Oxygen levels appeared to effectively influence the respective differentiation potential of
cultured MSC. While high oxygen tension was supporting osteogenesis and adipogenesis,
hypoxia greatly inhibited celluar differentiation into the osteogenic lineage. Moreover, the onset
of growth arrest was found to be delayed under reduced oxygen levels.
Taken these results together, the efficacy of corrective surgery of craniofacial anomalies using
bone transplantation, tissue engineering applications and regenerative technologies is depen-
dent on the age of MSC. In particular, we have experienced that MSC are sensitive to oxidative
stress, a fact which, we believe, is relevant for clinical therapy.
Gassner, Robert
Mechanical signalling affecting corrective surgery of craniofacial
anomalies (Se01-03)
Robert Gassner1, James Deschner2, Nick Piesco3, Sudha Agarwal4 (Robert.Gassner@uibk.
6 7
ac.at)
1: Department of Cranio-Maxillofacial Surgery, Medical University of Innsbruck; 2:Dental
School, University of Bonn; 3:Department of Oral Histology, University of Pittsburgh; 4:Division
of Oral Biology, Ohio State University
During wound healing following corrective surgery of craniofacial anomalies mechanical signals
play an important role. Such signals are observed at the interface of bone and teeth, where
osteoblast-like periodontal ligament (PDL) cells constantly take part in bone formation and
resorption in response to applied mechanical forces. Signals generated by tensile strain of low
magnitude (TENS-L) are antiinflammatory, whereas tensile strain of high magnitude (TENS-H)
is proinflammatory and catabolic. In this study, we examined the mechanisms of intracellular
actions of the antiinflammatory and proinflammatory signals generated by TENS of various
magnitudes. We show that both low and high magnitudes of mechanical strain exploit nuclear
factor (NF)-kappaB as a common pathway for transcriptional inhibition/activation of proin-
flammatory genes and catabolic processes. TENS-L is a potent inhibitor of interleukin (IL)-1
beta-induced I-kappaBbeta degradation and prevents dissociation of NF-kB from cytoplasmic
complexes and thus its nuclear translocation. This leads to sustained suppression of IL-1beta-
induced NF-kappaB transcriptional regulation of proinflammatory genes. In contrast, TENS-H is
a proinflammatory signal that induces I-kappaBbeta degradation, nuclear translocation of NF-
kappaB, and transcriptional activation of proinflammatory genes. In conclusion these findings
describe actions of applied tensile forces in osteoblast-like cells and have critical implications
in particular for surgical procedures of craniofacial anomalies.