Robust neurogenesis in chronic stroke monkeys following mesenchymal stem cell transplantation plus intermittent theta-burst stimulation
Summary
A significant population of chronic stroke patients urgently requires more effective therapies because of functional plateaus and limited intervention options. Intermittent theta-burst stimulation (iTBS) has been increasingly adopted in chronic-phase ischemic stroke management. However, the efficacy decreases over time. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic strategy for chronic stroke management through multiple mechanisms. Whether combined MSC transplantati
Content
# Robust neurogenesis in chronic stroke monkeys following mesenchymal stem cell transplantation plus intermittent theta-burst stimulation
*Published: 2026 Apr 24*
A significant population of chronic stroke patients urgently requires more
effective therapies because of functional plateaus and limited intervention
options. Intermittent theta-burst stimulation (iTBS) has been increasingly
adopted in chronic-phase ischemic stroke management. However, the efficacy
decreases over time. Mesenchymal stem cells (MSCs) have emerged as a promising
therapeutic strategy for chronic stroke management through multiple mechanisms.
Whether combined MSC transplantation and iTBS confers superior synergistic
efficacy warrants further investigation. In this study, human umbilical
cord-derived MSCs were stereotactically injected into the penumbra of the brain
parenchyma adjacent to infarct sites in cynomolgus monkeys with chronic-stage
middle cerebral artery occlusion (MCAO)-induced ischemic stroke. iTBS commenced
at 1 week post-transplantation (5 sessions/week until week 17). Behavioral
tests, electrophysiological recordings, functional magnetic resonance imaging
(fMRI), magnetic resonance spectroscopy (MRS), and plasma proteomic analysis
were conducted longitudinally, with terminal histological and spatial proteomic
analysis at week 17. The results indicated that combined MSC/iTBS therapy
enhanced motor function, reduced cortical excitation thresholds, shortened
motor-evoked potential (MEP) latency, increased neural activity
intensity/synchronization, strengthened functional connectivity, and optimized
motor cortex metabolism. In addition to the commonly attributed therapeutic
mechanisms of MSCs and iTBS, the combined therapy additionally triggered
neurogenesis and stem cell chemotaxis, which was potentially mediated by
iTBS-enhanced CXCL12 secretion from MSCs. Therefore, MSC/iTBS combination
therapy can effectively treat chronic stroke through multiple mechanisms,
particularly involving the activation of endogenous neural stem cells (NSCs),
representing a promising interdisciplinary treatment strategy.
DOI: 10.1038/s41392-026-02694-5