THE EVALUATION OF A BONE MARROW STROMAL STEM CELL-HYDROXYAPATITE COMPOSITE GRAFT FOR SPINAL FUSION. A RABBIT MODEL

Abstract

Introduction: Bone marrow derived stromal stem cells (BMSSC’s) have the ability to differentiate into a variety of mesenchymal tissues including bone. The objective of this study was to evaluate the use a hydroxyapatite – BMSSC (HA-BMSSC) composite graft for posterior spinal fusion in a rabbit model.

Method: The HA- BMSSC composite graft was prepared by seeding rabbit marrow derived BMSSC’s onto 5 grams of HA granules which were cultured for a further 7 days prior to implantation. Bilateral posterior L4–L5 interlamina spinal fusion was performed using the HA- BMSSC composite graft (4 Rabbits), hydroxyapatite(HA) granules (6 rabbits) or autologous bone graft obtained from the iliac crest (6 rabbits). Rabbits were sacrificed at 5 weeks. Fusion was assessed by manual palpation. Quantitative histological analysis of cartilage, fibrous tissue and bone in the mid portion of the graft was performed using image analysis software.

Results: Three of four of the HA- BMSSC grafts fused successfully compared to 5 of 6 of the autologous bone grafts and 0 of 6 of the HA control grafts. The fusion rate was significantly higher in the iliac crest and HA- BMSSC groups than the HA control group (p< 0.05). In both the HA control and HA stem cell composite grafts there was ingrowth of new bone and encasement of HA granules by new trabecular bone at the graft – host interface. Within the mid region of the grafts there was bone formation in 2 of four fusion masses in the HA- BMSSC group comprising 26% and 45% of tissue in the area examined. In contrast bone formation was seen in the centre of only one of the six 6 HA fusion masses and amounted to only 2% of tissue. There was no significant difference in average percentage area of new bone, cartilage or fibrous tissue within the central region of the HA and HA-BMSSC grafts. There was a higher mean percentage area of new bone formation within the autologous bone graft (27%) than the HA control group (0.3%). p< 0.02.

Discussion: The BMSSC –HA composite was as effective as autologous graft and superior to HA in promoting fusion, but HA when used alone was ineffective. A positive finding to support the osteogenic potential of the stem cell loaded HA granules was the presence of moderate amounts of enchondral new bone isolated within the central regions of the graft away from the graft host interface in 2 of 4 fusion masses. In contrast the HA control grafts only supported significant amounts of bone formation in the periphery, adjacent to the host bed.