Spinal fusion using adipose stem cells seeded on a radiolucent cage filler: a feasibility study of a single surgical procedure in goats
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To assess the feasibility of a one-step surgical concept, employing adipose stem cells (ASCs) and a novel degradable radiolucent cage filler (poly-L-lactide-co-caprolactone; PLCL), within polyetheretherketone cages in a stand-alone caprine spinal fusion model.
A double-level fusion study was performed in 36 goats. Four cage filler groups were defined: (i) acellular PLCL, (ii) PLCL + SVF (freshly harvested stromal vascular fraction highly enriched in ASCs); (iii) PLCL + ASCs (cultured to homogeneity); and (iv) autologous iliac crest bone graft (ABG). Fusion was assessed after 3 and 6 months by radiography, micro-CT, biomechanics, and biochemical analysis of tissue formed inside the cage after 6 months.
No adverse effects were observed in all groups. After 3 months, similar and low fusion rates were found. Segmental stability did not differ between groups in all tested directions. Micro-CT imaging revealed significantly higher amounts of mineralized tissue in the ABG group compared to all others. After 6 months, interbody fusion rates were: PLCL 53 %, SVF 30 %, ASC 43 % and ABG 63 %. A trend towards higher mineralized tissue content was found for the ABG group. Biochemical and biomechanical analyses revealed equal maturity of collagen cross-links and similar segmental stability between all groups.
This study demonstrates the technical feasibility and safety of the one-step surgical procedure for spinal fusion for the first time. The radiolucent PLCL scaffold allowed in vivo monitoring of bone formation using plain radiography. Addition of stem cells to the PLCL scaffolds did not result in adverse effects, but did not enhance the rate and number of interbody fusions under the current conditions. A trend towards superior results with ABG was found. Further research is warranted to optimize the spinal fusion model for proper evaluation of both PLCL and stem cell therapy.
KeywordsSpinal fusion Animal model Degradable polymers Stem cells Tissue engineering
The authors gratefully acknowledge Ger Vink, Klaas-Walter Meyer and Paul Sinnige from the University Animal Laboratory, for their invaluable help with the animal experiments and aftercare. The authors further like to acknowledge Dr. P. Gingras and Mr. P. Mulrooney for their help in designing and manufacturing the PLCL sheets used in this study. Finally, we would like to acknowledge Jessica Snabel from the Division of Biosciences, TNO Quality of Life, Leiden. The work of RJK has been supported by the Dutch Program for Tissue Engineering (Grant No. BGT 6734).
Conflict of interest
Bert van Rietbergen is a consultant for Scanco Medical AG.