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TREATMENT OF LARGE BONE DEFECTS WITH AUTOLOGOUS, CULTURED BONE MARROW STROMAL CELLS



Abstract

Large bone defect repair has always presented a difficult treatment problem. Marrow-derived osteogenic progenitor cells combined with hydroxyapatite (HA) were used for segmental bone reconstruction. The validity of this model has been shown for the repair of bone defects of critical size in large animal models. We used this cell-based therapeutic approach to treat three patients with large bone defects.

The patients were 41, 22 and 16 years old and had large tibial, ulnar and humeral diaphyseal gaps that ranged in size from 3.0 to 28.3 cm3. Marrow samples were harvested from the iliac crest and osteogenic progenitors isolated and expanded “ex vivo”. The expanded cells were then combined with a highly macroporous bioceramic scaffold whose size and shape reflected each individual bony defect. The cell/bioceramic composites were implanted at the lesion sites. External fixation was used to stabilise the grafts.

At present all patients have been followed up for 4–5 years. Already after the first month after surgery an initial integration at the bone/implant interface was evident. Bone formation in the implants, assessed by X-ray, progressed steadily in the follow-up period. Two patients achieved full functional recovery at 6 months after surgery, one patient at 12 months after surgery. The present report shows that large segmental bone reconstruction can be achieved in humans using osteoprogenitor cells. This technique can be improved by a more biodegradable and more biomechanically resistant scaffold use.