|Title||Mesenchymal Stem Cell-Seeded High-Density Collagen Gel for Annular Repair: 6-Week Results From In Vivo Sheep Models.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Hussain I, Sloan SR, Wipplinger C, Navarro-Ramirez R, Zubkov M, Kim E, Kirnaz S, Bonassar LJ, Härtl R|
|Date Published||2019 08 01|
|Keywords||Animals, Annulus Fibrosus, Collagen, Disease Models, Animal, Gels, Intervertebral Disc Degeneration, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Sheep, Tissue Engineering, Tissue Scaffolds|
BACKGROUND: Our group has previously demonstrated in vivo annulus fibrosus repair in animal models using an acellular, riboflavin crosslinked, high-density collagen (HDC) gel.
OBJECTIVE: To assess if seeding allogenic mesenchymal stem cells (MSCs) into this gel yields improved histological and radiographic benefits in an in vivo sheep model of annular injury.
METHODS: Fifteen lumbar intervertebral discs (IVDs) were randomized into 4 groups: intact, injury only, injury + acellular gel treatment, or injury + MSC-seeded gel treatment. Sheep were sacrificed at 6 wk. Disc height index (DHI), Pfirrmann grade, nucleus pulposus area, and T2 relaxation time (T2-RT) were calculated for each IVD and standardized to healthy controls from the same sheep. Quantitative histological assessment was also performed using the Han scoring system.
RESULTS: All treated IVDs retained gel plugs on gross assessment and there were no adverse perioperative complications. The MSC-seeded gel treatment group demonstrated statistically significant improvement over other experimental groups in DHI (P = .002), Pfirrmann grade (P < .001), and T2-RT (P = .015). There was a trend for greater Han scores in the MSC-seeded gel-treated discs compared with injury only and acellular gel-treated IVDs (P = .246).
CONCLUSION: MSC-seeded HDC gel can be delivered into injured IVDs and maintained safely in live sheep to 6 wk. Compared with no treatment and acellular HDC gel, our data show that MSC-seeded HDC gel improves outcomes in DHI, Pfirrmann grade, and T2-RT. Histological analysis shows improved annulus fibrosus and nucleus pulposus reconstitution and organization over other experimental groups as well.