Stem Cells in Post-Stroke Regenerative Therapy: Current Role of Wharton’s Jelly Mesenchymal Stem Cells in the Orchestrum

Background/Objectives: Modern approaches for post-stroke rehabilitation cover mechanistically different ways—from physiotherapy to digital technologies. Among these approaches, stem cell-based therapy represents probably the most complex but promising strategy. Methods: We discuss the current state-of-the-art of using mesenchymal stem cells (MSCs) in post-stroke regenerative therapy. Despite relatively wide use of bone marrow and adipose tissue MSCs, these cells represent a more mature (“adult”) state, which limits their proliferative and regenerative potentials. Compared to the “adult” MSCs, less “mature” MSCs obtained from umbilical cord, specifically Wharton’s jelly MSCs (WJ-MSCs), demonstrate unique functional capabilities and are free from certain technical and ethical issues. Results: The molecular and cellular mechanisms of action of WJ-MSCs are thoroughly discussed in comparison with abundantly used “adult” types of MSCs. We also comparatively evaluate their preclinical and clinical application for treating post-stroke patients. Recent findings indicate that not only MSCs but also their secretome/exosomes (cell-free product) represent a therapeutically beneficial cellular drug in post-stroke recovery. Specially designed and carefully evaluated protocols, which preserve the bioactivity of the cell-free product intact, are mentioned. Neuroprotective and neuroreparative properties of cell-free products—secretome and exosomes—derived from Wharton’s jelly MSCs are summarized. Conclusions: Cell-free products obtained from WJ-MSCs are an innovative adjunct therapy for post-stroke disorders, despite certain challenges and limitations of this type of therapy still present. By further investigation of the molecular composition and biological mechanisms of the WJ-MSC secretome and exosomes, their clinical applicability in neuroinflammatory and neurodegenerative pathologies will be promoted.