Correspondence

Repair of Large Bone Defects with the Use of Autologous Bone Marrow Stromal Cells

N Engl J Med 2001; 344:385-386February 1, 2001

Article

To the Editor:

The reconstruction of large bone segments is an important clinical problem, and none of the approaches proposed thus far have proved very effective. In animals, repair and functional recovery of segmental bone defects have been reported with the use of marrow-derived osteoprogenitor cells grown on scaffolds of macroporous hydroxyapatite.1-3

We report the use of this cell-based tissue-engineering approach to treat three patients with large bone defects. Patient 1 was a 41-year-old woman with loss of a 4.0-cm segment of the mid-diaphysis of the right tibia as the result of an unsuccessful attempt at bone lengthening. Patient 2 was a 16-year-old girl with traumatic loss of a 4.0-cm segment of the distal diaphysis of the right ulna. Patient 3 was a 22-year-old man with loss of a 7.0-cm segment of the right humerus as a result of a plurifragmental fracture. The study protocol was approved by the ethics committees of the centers where the patients were treated, and all the patients gave written informed consent.

For each patient, osteoprogenitor cells were isolated from bone marrow and expanded ex vivo.4 These cells were placed on macroporous hydroxyapatite scaffolds, the size and shape of which reflected the particular bone defect in each patient, and implanted at the lesion sites. External fixation was provided initially for mechanical stability and was subsequently removed (6.5 months after surgery in Patient 1, 6 months after surgery in Patient 2, and 13 months after surgery in Patient 3). All patients recovered limb function. As of this writing, 27, 16, and 15 months, respectively, after surgery, the patients have reported no problems with the implants.

In all three patients, radiographs and computed tomographic scans revealed abundant callus formation along the implants and good integration at the interfaces with the host bones by the second month after surgery. Representative radiographs are shown in Figure 1Figure 1Radiographs Obtained before and after the Repair of Large Bone Defects in Three Patients.. With the use of a traditional bone-graft approach, recovery would have required 12 to 18 months, under the most favorable conditions and in the absence of complications.5

We believe that the use of culture-expanded osteoprogenitor cells grown on porous bioceramic scaffolds will result in substantial improvement in our ability to repair large defects in long bones.

Rodolfo Quarto, M.D.
Maddalena Mastrogiacomo, Ph.D.
Ranieri Cancedda, M.D.
Istituto Nazionale per la Ricerca sul Cancro, Genoa 16132, Italy

Sergei M. Kutepov, M.D.
Vladimir Mukhachev, M.D.
Alexander Lavroukov, M.D.
Ural Scientific Research Institute of Traumatology and Orthopedics, Ekaterinburg 620014, Russia

Elizaveta Kon, M.D.
Maurilio Marcacci, M.D.
Istituti Ortopedici Rizzoli, Bologna 40136, Italy

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