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.
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.
Authors: Caroline Constant; Warren W Hom; Dirk Nehrbass; Eric-Norman Carmel; Christoph E Albers; Moritz C Deml; Dominic Gehweiler; Yunsoo Lee; Andrew Hecht; Sibylle Grad; James C Iatridis; Stephan Zeiter Journal: JOR Spine Date: 2022-04-22
Authors: Andrea Friedmann; Andre Baertel; Christine Schmitt; Christopher Ludtka; Javorina Milosevic; Hans-Joerg Meisel; Felix Goehre; Stefan Schwan Journal: Int J Mol Sci Date: 2021-04-19 Impact factor: 5.923
Authors: J Du; R G Long; T Nakai; D Sakai; L M Benneker; G Zhou; B Li; D Eglin; J C Iatridis; M Alini; S Grad; Z Li Journal: Eur Cell Mater Date: 2020-01-03 Impact factor: 3.942
Authors: Rose G Long; Stephen J Ferguson; Lorin M Benneker; Daisuke Sakai; Zhen Li; Abhay Pandit; Dirk W Grijpma; David Eglin; Stephan Zeiter; Tanja Schmid; Ursula Eberli; Dirk Nehrbass; Theodor Di Pauli von Treuheim; Mauro Alini; James C Iatridis; Sibylle Grad Journal: JOR Spine Date: 2019-12-21