The spleen may be an important target of stem cell therapy for stroke

Abstract

Stroke is the most common cerebrovascular disease, the second leading cause of death behind heart disease and is a major cause of long-term disability worldwide. Currently, systemic immunomodulatory therapy based on intravenous cells is attracting attention. The immune response to acute stroke is a major factor in cerebral ischaemia (CI) pathobiology and outcomes. Over the past decade, the significant contribution of the spleen to ischaemic stroke has gained considerable attention in stroke research. The changes in the spleen after stroke are mainly reflected in morphology, immune cells and cytokines, and these changes are closely related to the stroke outcomes. Autonomic nervous system (ANS) activation, release of central nervous system (CNS) antigens and chemokine/chemokine receptor interactions have been documented to be essential for efficient brain-spleen cross-talk after stroke. In various experimental models, human umbilical cord blood cells (hUCBs), haematopoietic stem cells (HSCs), bone marrow stem cells (BMSCs), human amnion epithelial cells (hAECs), neural stem cells (NSCs) and multipotent adult progenitor cells (MAPCs) have been shown to reduce the neurological damage caused by stroke. The different effects of these cell types on the interleukin (IL)-10, interferon (IFN), and cholinergic anti-inflammatory pathways in the spleen after stroke may promote the development of new cell therapy targets and strategies. The spleen will become a potential target of various stem cell therapies for stroke represented by MAPC treatment.

15-PGDH Inhibition Activates the Splenic Niche to Promote Hematopoietic Regeneration

“…In the setting of extramedullary hematopoiesis (EMH), CXCL12+ and SCF+ stromal cell populations also promote HSPC activation and myelo-erythroid progenitor cell expansion 9 , while VCAM1+ macrophages retain HSPCs in the spleen 10 . These findings highlight the potential therapeutic utility of strategies to promote or limit EMH, to improve hematopoietic regeneration or limit inflammation mediated by spleen-derived myeloid cells, as occurs in cardio-and neuro-vascular disease 4,11,12 .…”

Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke

“…In addition to promoting anti-inflammatory and immunomodulatory effects, these factors induce anti-apoptotic effects and mobilize endogenous stem cells (NSC))/neural progenitor cells (NPCs) [ 76 ]. These factors are released into the surrounding environment via direct permeation or extracellular vesicles (EV), and directly ameliorate ischemic damage and down-regulate local as well as systemic inflammation via peripheral immune organs, such as the spleen and the thymus [ 77 , 78 ]. EVs are membrane structures of lipid bilayer nanoparticles that transport proteins, lipids, and nucleic acids through endocytosis.…”

Recent Advances in Cell-Based Therapies for Ischemic Stroke

“…BMSCs can also influence the microenvironment at an injury site through the secretion of anti-inflammatory factors or by decreasing interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels. They may also induce the secretion of antiapoptotic molecules and trophic factors that promote angiogenesis, immunomodulation, including inhibition of T-cell proliferation, promotion of regulatory T cell (Treg) function, and diminishment of IL-23/IL-17 expression, and increased axonal growth [37][38][39][40][41].…”