Tie2-enriched nucleus pulposus cell transplantation enables severity-independent disc repair in a canine model with induced and controlled disc degeneration severity.

Intervertebral disc (IVD) degeneration is characterized by extracellular matrix loss, impaired nucleus pulposus cell (NPC) function, and depletion of Tie2-positive NP progenitor cells, leading to progressive structural failure and potential pain. Although cell-based therapies are promising, their regenerative efficacy across different degeneration severities remains unclear. This study aims to assess whether Tie2-enriched NPC transplantation can induce structural regeneration independent of baseline degeneration severity. Human Tie2-enriched NPC products were formulated as an off-the-shelf (OTS) product in hyaluronic acid. Two canine models of induced IVD degeneration were used. In Part 1, degeneration was induced by NP aspiration, followed by saline or OTS cell injection. In Part 2, dogs were randomized to mild or severe degeneration, with severe degeneration including additional surgical punch extraction. Outcomes included radiographic disc height index (DHI), MRI over a 3-month follow-up period, as well as macroscopic and histological assessments and immunohistochemical evaluation of human cell persistence. OTS-NPC transplantation significantly improved DHI and histological scores compared to sham treatment in both study parts. Regenerative effects were observed in both mild and severe degeneration models, resulting in comparable structural outcomes. In short, Tie2-enriched OTS-NPC demonstrated regenerative efficacy across degeneration severities in a clinically relevant animal model, supporting further translational development.