期刊
OSTEOARTHRITIS AND CARTILAGE
卷 27, 期 7, 页码 1094-1105出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2019.04.002
关键词
Mesenchymal stem cell; Migration; CD146; Intervertebral disc; Degeneration
资金
- AO Foundation
- AOSpine International
- National Natural Science Foundation of China [81772333]
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. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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