Is Immunomodulation a Principal Mechanism Underlying How Cell-Based Therapies Enhance Stroke Recovery?

Abstract

Inflammation within the brain and in peripheral tissues contributes to brain injury following ischemic stroke. Therapeutic modulation of the inflammatory response has been actively pursued as a novel stroke treatment approach for decades, without success. In recent years, extensive studies support the high potential for cell-based therapies to become a new treatment modality for stroke and other neurological disorders. In this review, we explore different types of cellular therapies and discuss how they modulate central and peripheral inflammatory processes after stroke. Apart from identifying potential targets for cell therapy, we also discuss paracrine and immunomodulatory mechanisms of cell therapy.

Keywords: Cell-based therapy; Immune response; Inflammation; Microglia; Spleen; Stroke.

Fig. 1

Inflammatory cascade following stroke showing central and peripheral mechanisms. In brain, resident microglia are activated predominantly towards the proinflammatory M1 phenotype. Spleen contracts, releasing inflammatory cells and cytokines. Collectively, they contribute in worsening stroke size

Fig. 2

Cell therapy and its multitarget immunomodulatory function. In brain, cell therapy causes a phenotype shift of resident microglia towards an anti-inflammatory M2 phenotype. Entrapment in lungs reprograms alveolar macrophages, while in spleen they aid in release of anti-inflammatory factors, such as interleukin (IL)-4 and IL-10. Release of various trophic factors ensures increased neurogenesis and angiogenesis while decreasing apoptosis of neurons. Collectively, cell therapy reduces post-stroke inflammation and limits stroke expansion