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THE USE OF MESENCHYMAL STEM CELLS AND GROWTH FACTOR BMP-7 IN PAEDIATRIC SPINAL SURGERY



Abstract

There can be no doubt that bone morphogenetic proteins play a hierarchic role in the osteogenetic cascade. Pre-clinical and clinical trials have confirmed their decisive role in achieving anterior lumbar fusion, as they direct mesenchymal stem cells toward osteoblastic lineages.The present study is concerned with initial experience in the application of autologous mesen-chymal stem cells and various growth factors (BMP-7,VEGF,TGFbeta) in the treatment of paediatric spinal pathologies.

Eleven patients affected by serious forms of congenital infantile scoliosis, idiopathic scoliosis and grade I spondylolisthesis received surgical treatment. In three patients with congenital infantile scoliosis, ages ranging from 3 to 12 years, the surgical procedure was an anterior and posterior fusion at the level of the hemiver-tebra, extending it to a level above and below it by means of in situ decortication of the vertebral plates and laminae on the convex side and delivery of stem cells taken from the iliac bone and applied in situ by means of bovine collagen sponge (Healos system). No fixation device was added. Plaster and brace were used during the postoperative course for 9 months. In two cases of intertransverse in situ fusion for grade I spondylolisthesis the age of the patients was 13 and 16 years, respectively, and the surgical procedure consisted in the standard technique to which was added delivery of a mixture composed of small bone chips obtained from decortication, 3.5 mg of eptotermin alpha (Op-1, BMP7), and autologous stem cells taken from iliac bone. A special form of informed consent was obtained for these two patients because of their incomplete bone maturity. TLSO was used in the postoperative course for 2 months. In the six patients with idiopathic scoliosis, ages ranged from 13 to 15 years and the treatment consisted in posterior instrumentation and fusion by means of rods, transpedicular screws and hooks; standard fusion techniques were supported by local bone chips obtained from decortication, placed on collagen sponges and combined with autologous stem cells taken from iliac bone with the addition of platelet gel derived from the autologous preoperative blood collection. No bone chips were taken from iliac wing. The results were evaluated by X-rays and CT at intervals of 1, 2, 4, 6 and 12 months.

In the cases of congenital scoliosis a solid fusion area was obtained only for posterior hemiephysiodesis, without a parallel bone signal of fusion at the anterior level. In the cases of intertransverse in situ fusions for spondy-lolisthesis there was a beginning fusion already visible on the first X-ray control 1 month postopoeratively, confirmed at successive check-ups and maintained in the follow-up. The cases of idiopathic scoliosis showed an initial ossification of the grafts and signals of fusion at the 6-month check-up.

The isolated use of stem cells, although promising from a theoretical point of view, did not prove encouraging in the cases of anterior fusion. It is most probable that the absence of instrumentation induced a defect in the stable fixation of the fused segments, the latter being a crucial factor.The cases of in situ fusion for spondylolisthesis confirm the hierarchic role of the bone morphogenetic protein 7 in inducing the mesenchymal stem cells, released in situ from decortication, toward osteoblastic lineage. To our knowledge these represent the first two cases of use of OP-1 in patients younger than 18 years. In the fusion areas which are more extensive in length (idiopathic scoliosis) the added use of autologous stem cells mixed with platelet gel seems to improve the physiological processes of fusion. It will be necessary to monitor the long-term results of these procedures with special regard to loss of correction and weakness of the fusion area causing torsional or flexion-extension stress. These possible costs have to be compared with the verified benefits of a better use of blood in its capacity to save on corresponding haemotransfusion, combined with the absence of comorbidity related to the donor site of iliac bone chips.