title: Transplanted xenogenic bone marrow stem cells survive and generate new bone formation in the posterolateral lumbar spine of non-immunosuppressed rabbits.
abstract: Bone marrow stem cells (BMSCs) are pluripotent cells that have been used to facilitate bone repair because of their capability of differentiating into osteoblasts. However, it is well known that the number of BMSCs with osteogenic potential decreases in patients with old age, osteoporosis, and metabolic diseases. In such conditions, xenogenic BMSCs may provide an alternative to autologous BMSCs. In the current study, we investigated the potential of transplanted xenogenic BMSCs to survive and generate new bone formation in the posterolateral lumbar spine of non-immunosuppressed rabbits. The BMSCs were obtained from bilateral femurs of four male rats, cultured and expanded in medium with osteoinduction supplement. The BMSCs (1,000,000 cells) of male rats loaded onto 5 cc compression resistant matrix (CRM; Medtronic Sofamor Danek, USA) were implanted bilaterally onto the L4-5 intertransverse processes of 16 female rabbits (xenogenic BMSCs + CRM group). The 16 female rabbits that received 5 cc CRM alone were used as controls (CRM alone group). To exclude the possibility of migration of BMSCs from the transverse processes of the recipient rabbits, we did not decorticate the transverse processes. No rabbits received any immunosuppressive medications during the experiment. Four rabbits each in both of the experimental and control groups were killed at 1, 2, 4, and 6 months postimplantation, and the lumbar spine underwent radiological and histological analyses for evaluation of new bone formation. The polymerase chain reaction (PCR) for Sry gene (Y-chromosome-specific marker) was used to evaluate the survival of transplanted xenogenic BMSCs. The expression of Sry gene was clearly identified in the lumbar spines of all the 16 rabbits in the xenogenic BMSCs + CRM group at 1-6 months postimplantation. Serial plain radiographs showed gradual resorption of CRM; however, it was difficult to clearly identify the presence of new bone formation due to the radiopacity of the remaining CRM. Histologically, mature lamellar and woven bone with osteoblasts and osteocytes were identified in all eight rabbits in the xenogenic BMSCs + CRM group at 4 and 6 months postimplantation, but in none of the eight rabbits at 1 and 2 months postimplantation. None of CRM alone group showed new bone formation at 1-6 months postimplantation. Mild-to-moderate infiltration of inflammatory cells was identified around the CRM carriers in both the groups. No post-operative wound infection was found in either group. Our results indicate that xenogenic BMSCs loaded onto CRM survive and generate new bone formation when placed into the posterolateral lumbar spine of rabbits without immunosuppression. To determine if a solid fusion can be achieved with such techniques, further studies are needed to investigate the appropriate dose of xenogenic BMSCs, amounts of CRM, and the requisite incubation time.
authors.affiliation: Department of Orthopaedic Surgery, Uijeongbu St Mary's Hospital, The Catholic University of Korea School of Medicine, Uijongbu, South Korea.
authors.forename: Hyung-Jun
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jong-Beom
authors.initials: JB
authors.lastname: Park
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Lee
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Park
authors.forename: Eun-Ae
authors.initials: EA
authors.lastname: Park
authors.forename: K Daniel
authors.initials: KD
authors.lastname: Riew
authors.forename: Seung-Koo
authors.initials: SK
authors.lastname: Rhee
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000379:methods*; D001857:Bone Matrix / Q000637:transplantation; D001861:Bone Regeneration / Q000502:physiology*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D005260:Female; D006085:Graft Survival / Q000502:physiology; D007165:Immunosuppression Therapy; D008159:Lumbar Vertebrae / Q000166:cytology / Q000502:physiology / Q000601:surgery*; D008297:Male; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D010011:Osteocytes / Q000166:cytology / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology; D010024:Osteoporosis / Q000601:surgery; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D051876:Sex-Determining Region Y Protein / Q000235:genetics; D033581:Stem Cell Transplantation / Q000379:methods*; D014183:Transplantation, Heterologous / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D051876:Sex-Determining Region Y Protein; C497747:Sry protein, rat