Allogeneic mesenchymal precursor cells (MPCs) combined with an osteoconductive scaffold to promote lumbar interbody spine fusion in an ovine model.
BACKGROUND
Advances in immunomagnetic cell sorting have enabled isolation and purification of pleuripotent stem cells from marrow aspirates and have expanded stem cell therapies to include allogeneic sources.


OBJECTIVE
This study aimed to determine the safety and efficacy of allogeneic mesenchymal precursor cells (MPCs) combined with an osteoconductive scaffold in lumbar interbody spinal fusion using an ovine model.


METHODS
Thirty-two skeletally mature ewes underwent a single-level interbody fusion procedure using a Polyetheretherketone fusion cage supplemented with either iliac crest autograft (AG) or an osteconductive scaffold (Mastergraft Matrix, Medtronic, Memphis, TN, USA) with 2.5×10(6) MPCs, 6.25×10(6) MPCs, or 12.5×10(6) MPCs.


METHODS
Plain radiographs and computed tomography scans were scored for bridging bone at multiple points during healing and at necropsy. The biomechanical competency of fusion was scored by manual palpation and quantified using functional radiographs at necropsy. Postnecropsy histopathology and histomorphometric analysis assessed the local response to MPC treatment and quantified the volume and connectivity of newly formed bridging bone. Safety was assessed by serum biochemistry, hematology, and organ histopathology.


RESULTS
Mesenchymal precursor cell treatment caused no adverse systemic or local tissue responses. All analyses indicated MPCs combined with an osteoconductive scaffold achieved similar or better fusion success as AG treatment after 16 weeks, and increasing the MPC dose did not enhance fusion. Manual palpation of the fusion site indicated more than 75% of MPC-treated and 65% of AG-treated animals achieved rigid fusion, which was corroborated with functional radiography. Computed tomography fusion scores indicated all animals in the MPC- and AG-treatment groups were fused at 16 weeks, yet X-ray scores indicated only 67% of the AG-treated animals were fused. Histomorphometry analyses showed equivalent outcomes for fusion connectivity and bony fusion area for MPC- and AG-treated groups. Approximately 6% residual graft material remained in the MPC-treated fusion sites at 16 weeks.


CONCLUSIONS
Adult allogeneic MPCs delivered using an osteoconductive scaffold were both safe and efficacious in this ovine spine interbody fusion model. These results support the use ofallogeneic MPCs as an alternative to AG for lumbar interbody spinal fusion procedures.
BioSolutions Consulting LLC, 3416 Henderson Circle, Santa Rosa, CA 95403, USA. Electronic address: donna.wheeler@biosoln.com.
Donna L
DL
Wheeler
Bone Healing Research Laboratory, Iowa Spine Research Laboratory, University of Iowa, 100 Oakdale Campus #259 ORB, Iowa City, IA 52242, USA.
Douglas C
DC
Fredericks
Central Texas Spine Institute, 6818 Austin Center Blvd., #200, Austin, TX 78731, USA.
Randall F
RF
Dryer
The Spine Institute, Center for Spinal Restoration, 2811 Wilshire Blvd., Suite 850, Santa Monica, CA 90403, USA.
Hyun W
HW
Bae
D000818:Animals; D001577:Benzophenones; D001672:Biocompatible Materials; D016025:Bone Transplantation / Q000379:methods*; D005260:Female; D007085:Ilium / Q000637:transplantation*; D007659:Ketones; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000601:surgery*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells; D011092:Polyethylene Glycols; D011108:Polymers; D012756:Sheep; D013123:Spinal Fusion / Q000379:methods*; D054457:Tissue Scaffolds; D014057:Tomography, X-Ray Computed; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D001577:Benzophenones; D001672:Biocompatible Materials; D007659:Ketones; D011108:Polymers; C063834:polyetheretherketone; D011092:Polyethylene Glycols
Biomechanics; Bone graft substitute; Computed tomography; Histomorphometry; Histopathology; Mesenchymal stem cells; Ovine lumbar interbody fusion; Plain radiographs