Cell homing in the degenerative intervertebral disc: characterization of migrating cells and their regenerative potential (DISCREGEN2)

Background

Homing of human mesenchymal stem cells (MSCs) has been described as potential alternative to MSC injection, aiming to enhance the regenerative capacity of the intervertebral disc (IVD). However, the effect of MSC homing on the IVD cells is not well known yet.

a) Isolation of MSCs from vertebral bone marrow aspirate by plastic adherence. MSCs were labeled and labeling was confirmed by flow cytometry. b) IVDs with endplates were isolated from bovine tails. Adjacent IVDs were randomly assigned to: time point zero ctrl (T0), day 5 untreated control (ctrl) and day 5 treated disc by MSC homing (treated). c) Human IVD tissue was isolated during surgery or from organ donors. Tissue from one donor was divided in halves. One half was treated by MSC homing (treated), the second half was used as untreated control (ctrl).

Goal

To investigate the effect of MSC homing on the IVD progenitor cell population, the IVD cell survival and their proliferative response.

Results

Human MSCs were isolated from vertebral bone marrow aspirates, labeled and seeded onto the endplate of bovine IVDs and human IVD tissue. Following MSC migration for 5 days, IVD cells were isolated by tissue digestion. The fractions of IVD progenitor cells, dead, apoptotic, and proliferative IVD cells were evaluated by flow cytometry and compared to untreated IVDs. For human IVDs, three groups were investigated: non-degenerated (organ donors), IVDs of patients suffering from spinal trauma, and degenerative IVD tissue samples. MSC homing enhanced the fraction of IVD progenitor cells in bovine and human IVD samples. Furthermore, a significant proliferative response and lower fraction of dead cells were observed after MSC homing in both bovine and human IVD tissues. Our findings indicated that MSC homing enhanced the survival and regenerative capability of IVD cells, which may be mediated by intercellular communication. MSC homing could represent a potential treatment strategy to prevent the onset of the degenerative cascade in IVDs at risk such as IVDs adjacent to a fused segment or IVDs after herniation.

Publication

Wangler S, Menzel U, Li Z, Ma J, Hoppe S, Benneker LM, Alini M, Grad S, Peroglio M. CD146/MCAM distinguishes stem cell subpopulations with distinct migration and regenerative potential in degenerative intervertebral discs. Osteoarthritis Cartilage 27(7):1094-1105, 2019.

Wangler S, Peroglio M, Menzel U, Benneker LM, Haglund L, Sakai D, Alini M, Grad S. Mesenchymal stem cell homing into intervertebral discs enhances the Tie2 positive progenitor cell population, prevents cell death and induces a proliferative response. Spine (Phila Pa 1976) 44(23):1613-1622, 2019.

Wangler S. Stem cell homing towards degenerative intervertebral discs: characterization of the migrating subpopulation and its regenerative potential. 2020 Universität Bern (M. Alini, L.M. Benneker, M. Peroglio) – MD & PhD (thesis)
Presentation

Wangler S, Peroglio M, Menzel U, Benneker LM, Haglund L, Sakai D, Alini M, Grad S. MSC homing facilitates IVD cell survival, proliferation and enhances the Tie2 positive IVD progenitor cell subpopulation, BioSpine 2019, Rom, IT (podium)

Wangler S, Peroglio M, Li Z, Menzel U, Benneker LM, Richards RG, Alini M, Grad S. Homing of Mesenchymal Stem Cells into Degenerated Intervertebral Discs - An Alternative to Stem Cell Injection? Global Spine Congress 2019, Toronto, CA (poster)

Wangler S, Peroglio M, Menzel U, Benneker LM, Haglund L, Sakai D, Alini M, Grad S. MSC homing into intervertebral discs enhances the Tie2 positive progenitor cell population, prevents cell death and induces a proliferative response. ISSLS Conference 2019, Kyoto, JP (special poster)
Partner

Benneker L (Prof), Inselspital Bern, Switzerland

Sakai D (Prof), Tokai University School of Medicine, Japan

Haglund L (Prof), Montreal General Hospital, Montreal, Canada