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

Wangler, S; Menzel, U; Li, Z; Ma, J; Hoppe, S.; Benneker, L. M.; Alini, M; Grad, S; Peroglio, M (2019). CD146/MCAM distinguishes stem cell subpopulations with distinct migration and regenerative potential in degenerative intervertebral discs. Osteoarthritis and cartilage, 27(7), pp. 1094-1105. Elsevier 10.1016/j.joca.2019.04.002

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery

UniBE Contributor:

Hoppe, Sven and Benneker, Lorin Michael

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1063-4584

Publisher:

Elsevier

Language:

English

Submitter:

Kathrin Aeschlimann

Date Deposited:

28 Jan 2020 09:43

Last Modified:

28 Jan 2020 09:50

Publisher DOI:

10.1016/j.joca.2019.04.002

PubMed ID:

31002939

Uncontrolled Keywords:

CD146 Degeneration Intervertebral disc Mesenchymal stem cell Migration

BORIS DOI:

10.7892/boris.138589

URI:

https://boris.unibe.ch/id/eprint/138589

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