Repair of large bone defects by autologous human bone marrow stromal cells

Several approaches have been proposed for large bone defect repair, but non has proven ideal so far. We have published that marrow-derived osteogenic progenitor cells combined with hydroxyapatite (HA) promote segmental healing of critical size bone defects in sheep. Here we describe the use of this tissue engineering, cell-based therapeutic approach to treat 3 patients with large bone defects. 41, 22 and 16 year old patients presented large tibial, ulnar and humeral diaphysealgaps ranging in size from 3,0 to 28,3 cm³. Osteogenic progenitors were isolated from bone marrow, expanded 'ex vivo', and combined with highly macroporous bioceramic scaffolds. Cell/bioceramic composites, whose size and shape reflected each bone defect, were implanted at the lesion sites. External fixation was used to stabilize the grafts. Evaluation included clinical, radiographic and computerized tomography examination. Patients were followed for 10 to 23 months. An initial integration at the bone/implant interface was already evident one month after surgery. Bone formation, assessed by x-ray analysis, progressed steadily during the following months. External fixation was removed after 5 and 6 months in two patients. A full functional recovery of the treated limb occurred within 6 to 7 months after surgery. In the third patient a mechanical loosening of the external fixator occurred; therefore, 6 months after surgery a different fixation device was placed for additional 3 months. Large segmental bone reconstruction can be achieved in humans, over a relatively short time, by autologous osteoprogenitor cells delivered by macroporous bioceramic scaffolds.