S Wangler1, U Menzel2, Z Li3, J Ma4, S Hoppe5, L M Benneker6, M Alini7, S Grad8, M Peroglio9. 1. AO Research Institute Davos, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland. Electronic address: Sebastian.Wangler@aofoundation.org. 2. AO Research Institute Davos, Switzerland. Electronic address: Ursula.Menzel@aofoundation.org. 3. AO Research Institute Davos, Switzerland. Electronic address: Zhen.Li@aofoundation.org. 4. AO Research Institute Davos, Switzerland. Electronic address: Junxuan.Ma@aofoundation.org. 5. Inselspital, University of Bern, Switzerland. Electronic address: Sven.Hoppe@insel.ch. 6. Inselspital, University of Bern, Switzerland. Electronic address: LorinMichael.Benneker@insel.ch. 7. AO Research Institute Davos, Switzerland. Electronic address: Mauro.Alini@aofoundation.org. 8. AO Research Institute Davos, Switzerland. Electronic address: Sibylle.Grad@aofoundation.org. 9. AO Research Institute Davos, Switzerland. Electronic address: Marianna.Peroglio@aofoundation.org.
Abstract
OBJECTIVE: This study aimed to characterize the mesenchymal stem cell (MSC) subpopulation migrating towards a degenerated intervertebral disc (IVD) and to assess its regenerative potential. DESIGN: Based on initial screening for migration towards C-C motif chemokine ligand 5 (CCL5), the migration potential of CD146+ and CD146- mesenchymal stem cells (MSCs) was evaluated in vitro and in a degenerated organ culture model (degeneration by high-frequency loading in a bioreactor). Discogenic differentiation potential of CD146+ and CD146- MSCs was investigated by in vitro pellet culture assay with supplementation of growth and differentiation factor-6 (GDF6). Furthermore, trypsin degenerated IVDs were treated by either homing or injection of CD146+ or CD146- MSCs and glycosaminoglycan synthesis was evaluated by Sulphur 35 incorporation after 35 days of culture. RESULTS: Surface expression of CD146 led to a higher number of migrated MSCs both in vitro and in organ culture. CD146+ and CD146- pellets responded with a similar up-regulation of anabolic markers. A higher production of sulfated glycosaminoglycans (sGAG)/DNA was observed for CD146+ pellets, while in organ cultures, sGAG synthesis rate was higher for IVDs treated with CD146- MSCs by either homing or injection. CONCLUSIONS: The CD146+ MSC subpopulation held greater migration potential towards degenerative IVDs, while the CD146- cells induced a stronger regenerative response in the resident IVD cells. These findings were independent of the application route (injection vs migration). From a translational point of view, our data suggests that CD146+ MSCs may be suitable for re-population, while CD146- MSCs may represent the primary choice for stimulation of endogenous IVD cells.
OBJECTIVE: This study aimed to characterize the mesenchymal stem cell (MSC) subpopulation migrating towards a degenerated intervertebral disc (IVD) and to assess its regenerative potential. DESIGN: Based on initial screening for migration towards C-C motif chemokine ligand 5 (CCL5), the migration potential of CD146+ and CD146- mesenchymal stem cells (MSCs) was evaluated in vitro and in a degenerated organ culture model (degeneration by high-frequency loading in a bioreactor). Discogenic differentiation potential of CD146+ and CD146- MSCs was investigated by in vitro pellet culture assay with supplementation of growth and differentiation factor-6 (GDF6). Furthermore, trypsin degenerated IVDs were treated by either homing or injection of CD146+ or CD146- MSCs and glycosaminoglycan synthesis was evaluated by Sulphur 35 incorporation after 35 days of culture. RESULTS: Surface expression of CD146 led to a higher number of migrated MSCs both in vitro and in organ culture. CD146+ and CD146- pellets responded with a similar up-regulation of anabolic markers. A higher production of sulfated glycosaminoglycans (sGAG)/DNA was observed for CD146+ pellets, while in organ cultures, sGAG synthesis rate was higher for IVDs treated with CD146- MSCs by either homing or injection. CONCLUSIONS: The CD146+ MSC subpopulation held greater migration potential towards degenerative IVDs, while the CD146- cells induced a stronger regenerative response in the resident IVD cells. These findings were independent of the application route (injection vs migration). From a translational point of view, our data suggests that CD146+ MSCs may be suitable for re-population, while CD146- MSCs may represent the primary choice for stimulation of endogenous IVD cells.
Authors: Paola Bermudez-Lekerika; Katherine B Crump; Sofia Tseranidou; Andrea Nüesch; Exarchos Kanelis; Ahmad Alminnawi; Laura Baumgartner; Estefano Muñoz-Moya; Roger Compte; Francesco Gualdi; Leonidas G Alexopoulos; Liesbet Geris; Karin Wuertz-Kozak; Christine L Le Maitre; Jérôme Noailly; Benjamin Gantenbein Journal: Front Cell Dev Biol Date: 2022-06-29
Authors: Zoltán Veréb; Anett Mázló; Attila Szabó; Szilárd Póliska; Attila Kiss; Krisztina Litauszky; Gábor Koncz; Zoltán Boda; Éva Rajnavölgyi; Attila Bácsi Journal: Stem Cells Int Date: 2020-10-21 Impact factor: 5.443