Aim

The aim of this study was to analyze our results using a modular endoprosthetic replacement system (MUTARS) for bone tumours of the proximal humerus.

Mesenchymal stem cells (MSC) are suitable candidates for the cell-based cartilage reconstruction and have been isolated from different sources such as bone marrow (BMSC), adipose tissue (ATSC) and synovium (SMSC). The aim of this study was to analyse the tendency of BMSC, ATSC and SMSC to undergo hypertrophy during chondrogenic induction in vitro and to evaluate their in vivo development after ectopic transplantation into SCID mice in order to determine which cell source is most suitable for cartilage regeneration.

Human BMSC, ATSC and SMSC were cultured under chondrogenic conditions for five weeks. Differentiation was evaluated based on histology, gene expression, and analysis of alkaline phosphatase activity (ALP). Pellets were transplanted subcutaneously into SCID mice after chondrogenic induction for 5 weeks and analysed 4 weeks later by histology. Similar COL2A1:COL10A1 mRNA ratios were found in BMSC, ATSC and SMSC. BMSC displayed the highest ALP activities, SMSC had lower and heterogenic ALP activities in vitro which correlated with calcification of spheroids in vivo. Most SMSC transplants specifically lost their collagen type II in vivo or were fully degraded. BMSC and ATSC pellets always underwent vascular invasion and calcification in vivo. Single BMSC samples had the capacity to develop into woven bone or fully developed ossicles with hematopoietic tissue surrounded by a bone capsule.

Neither BMSC nor ATSC or SMSC were able to form stable ectopic cartilage. While BMSC and ATSC underwent developmental processes related to endochondral ossification instead of stable ectopic cartilage formation, SMSC tended to undergo fibrous dedifferentiation or degradation. Besides appropriate induction of chondrogenesis, locking of cells in the desired differentiation state is, thus, a further challenge for adult stem cell-based cartilage repair.

Introduction: Osteoporosis, a major public health burden, is associated with increased fracture risk. Fracture healing in osteoporosis is altered with reduced callus formation and impaired biomechanical properties of newly formed bone leading to high risk of fixation failure. Experimental data have shown decreased healing potential in aged animals and in animal models of post-menopausal bone loss. It is unclear whether fracture healing is similarly impaired in senile osteoporosis. The objective of this study is to investigate fracture healing in a small animal model of senile osteoporosis, senescence-accelerated mouse prone 6 (SAMP6).

Materials & Methods: A mid-femur osteotomy was created in SAMP6-mice (n=24) and senescence-resistant inbred strains (SAMR1) (n=24) were used as controls. The osteotomy was rigidly fixed using a newly developed screw-plate-implant (MouseFix). Fracture healing was evaluated at 7, 14, 28 and 42 days after surgery using micro-CT and histomorphometry. Biochemical marker for bone formation (osteocalcin) and bone resorption (TRAP5b) were evaluated from serum samples. MSC were extracted from the femurs of mice and cultured in vitro and differentiated into either osteoblasts or adipocytes using standard induction media.

Results: Studies carried out in vitro confirmed that MSC isolated from the bone marrow of SAMP6 mice had a reduced tendency to differentiate toward the osteoblast cell lineage as previously reported in human osteoporotic patients. Although osteoblastogenesis was clearly impaired, the formation of new bone in SAMP6 mice was comparable to that observed in SAMR1 mice. Similar results were found for histomorphometry data analyzing the degree of bone mineralisation. Interestingly, osteocalcin levels were significantly increased in serum samples from osteoporotic mice at day 7 and 14 following fracture.

Discussion: The data presented here indicates that fracture healing proceeds normally in a mouse model for senile osteoporosis. This finding supports the clinical observation that although fracture fixation is difficult in osteoporosis, healing potential seems to be unchanged. MSC from osteoporotic patients as wells as from SAMP6-mice show reduced proliferation rate together with adipogenic rather than osteogenic differentiation pattern. However, decreased cell dynamics seems not to influence diaphyseal fracture healing. Other sources of MSC other than bone marrow-derived MSC may therefore be pivotal in determining the outcome of intramembranous bone repair in both normal and osteoporotic bone.