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Osteoarthritis Cartilage. 2019 Jul;27(7):1094-1105. doi: 10.1016/j.joca.2019.04.002. Epub 2019 Apr 16.

CD146/MCAM distinguishes stem cell subpopulations with distinct migration and regenerative potential in degenerative intervertebral discs.

Author information

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.

KEYWORDS:

CD146; Degeneration; Intervertebral disc; Mesenchymal stem cell; Migration

PMID:
31002939
DOI:
10.1016/j.joca.2019.04.002

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