Therapeutic Window for Intravenous Human Muse Cell Administration in Mouse Spinal Cord Injury

Area of Science:

• Regenerative Medicine
• Neuroscience
• Stem Cell Biology

Background:

• Multipotent adult stem cells, specifically Multilineage-differentiating stress-enduring (Muse) cells, represent a unique subpopulation of mesenchymal stromal cells (MSCs).
• The optimal timing for stem cell therapy in spinal cord injury (SCI) is crucial, as the acute post-injury environment can be hostile to cell survival and efficacy.

Purpose of the Study:

• To investigate the therapeutic window for intravenous Muse cell administration in a mouse model of severe spinal cord injury (SCI).
• To compare the efficacy of Muse cells with bone marrow-derived mesenchymal stromal cells (BM-MSCs) at different time points post-injury.

Main Methods:

• Severe T9 contusion SCI was induced in C57BL/6J mice.
• Human bone marrow-derived Muse cells or BM-MSCs were administered intravenously at 2, 8, 14, or 28 days post-injury (DPI) without immunosuppressants.
• Locomotor recovery was assessed using the Basso Mouse Scale, and cell homing, engraftment, and neural differentiation in the injured spinal cord were evaluated.

Main Results:

• Intravenous Muse cell administration at 2 DPI significantly improved locomotor recovery compared to BM-MSCs and vehicle controls.
• Muse cells administered at 2 DPI demonstrated enhanced homing to the injured spinal cord, persistent engraftment, and expression of neural lineage markers.
• Ablation of engrafted Muse cells at day 42 partially reversed the observed locomotor recovery, indicating their contribution to functional improvement.

Conclusions:

• Intravenous Muse cell therapy for SCI is timing-dependent, with significantly greater therapeutic efficacy when administered during the early post-injury phase.
• Early administration of Muse cells promotes locomotor recovery and functional improvement in SCI models.
• Muse cells hold promise for early-stage therapeutic interventions in spinal cord injury.