Mesenchymal Stem Cell Homing Into Intervertebral Discs Enhances the Tie2-positive Progenitor Cell Population, Prevents Cell Death, and Induces a Proliferative Response

Abstract

Study Design. Experimental study with human mesenchymal stem cells (MSCs) and intervertebral disc (IVD) tissue samples. Objective. This study aimed to characterize the effect of MSC homing on the Tie2-positive IVD progenitor cell population, IVD cell survival, and proliferation. Summary of Background Data. Homing of human MSCs has been described as potential alternative to MSC injection, aiming to enhance the regenerative capacity of the IVD. IVD cells expressing Tie2 (also known as CD202b or Angiopoietin-1 receptor TEK tyrosine kinase) represent a progenitor cell population with discogenic differentiation potential. However, the fraction of Tie2-positive progenitor cells decreases with aging and degree of IVD degeneration, resulting in a potential loss of the IVD's regenerative capacity. Methods. Human MSCs, isolated from vertebral bone marrow aspirates, were 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 Tie2-positive, dead, apoptotic, and proliferative IVD cells were evaluated by flow cytometry and compared to untreated IVDs. For human IVDs, 3 groups were investigated: nondegenerated (organ donors), IVDs of patients suffering from spinal trauma, and degenerative IVD tissue samples. Results. MSC homing enhanced the fraction of Tie2-positive IVD cells in bovine and human IVD samples. Furthermore, a proliferative response and lower fraction of dead cells were observed after MSC homing in both bovine and human IVD tissues. Conclusion. Our findings indicate that MSC homing enhances 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.

Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis

“…MIP-1α has been associated with inhibition of cell proliferation [ 45 ]. Release of MIP-1α might therefore represent an autoregulation of cell proliferation, as the intact healthy environment does not require an enriched cell population [ 46 , 47 ]. Concerning ECM turnover, we observed an upregulated release of alpha 2 macroglobulin (A2M) (Table 1 ).…”

The Application of Mesenchymal Stromal Cells and Their Homing Capabilities to Regenerate the Intervertebral Disc

“…Another approach to investigate the influence of homed MSCs on degenerated IVDs was taken by Wangler et al In brief, human MSCs were seeded on bovine whole IVDs and on either healthy, traumatic, or degenerated human IVD tissues [105]. After a period of MSC homing into the IVDs, they evaluated the cells' effect on the host's Tie2 progenitor cell populations, the IVD cell survival, and proliferation.…”

Bone Marrow Concentrate (BMC) Therapy in Musculoskeletal Disorders: Evidence-Based Policy Position Statement of American Society of Interventional Pain Physicians (ASIPP)

“…The role of MSCs in healing and regeneration by studying autologous BMC MSC migration into the injured intervertebral disc has been investigated (384)(385)(386)(387)(388)(389). MSC homing has been reported to play a role in the endogenous regeneration of different skeletal tissues, including bone and cartilage.…”

“…In the intervertebral disc, recruitment of bone marrow cells toward the regenerating intervertebral disc has been demonstrated in a mouse tail model in vivo. However, the findings from the intervertebral disc degeneration model suggests that the pool of available cells or their recruitment efficiency may need to be enhanced by exogenous means to achieve a significant regenerative effect (384). Thus, migration of exogenously delivered BM-MSCs through the endplate into the intervertebral disc has been described as an alternative approach for intradiscal cell treatment in several whole intradiscal organ culture models (388)(389)(390)(391).…”