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MAPCs Promote Recovery from Stroke via the Spleen!

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Review of “Multipotent Adult Progenitor Cells Enhance Recovery after Stroke by Modulating the Immune Response from the Spleen” from STEM CELLS by Stuart P. Atkinson

Many stem cell-based therapies for stroke aim to directly enhance endogenous repair mechanisms within the brain; however, recent studies have suggested that systemic changes to the immune system may have a greater impact [1]. Of the peripheral immune organs, the spleen responds to brain injury by releasing immune cells and pro-inflammatory mediators that can exacerbate damage [2, 3].

Bone marrow-derived multipotent adult progenitor cells (MAPCs) exert potent immunomodulatory effects and improve neurological outcomes in a variety of disease models. Importantly, recent trial results indicate that MAPCs may represent a safe and effective treatment option for ischemic stroke [4]. Now, a new STEM CELLS study from the laboratory of Sean I. Savitz (McGovern Medical School at UT-Health, Houston, Texas, USA) has sought to understand if MAPCs affect the spleen and how this impacts recovery from stroke [5].

Initial gene expression analysis indicated that systemic MAPC treatment broadly attenuated the immune inflammatory response in the rat brain following the induction of ischemic stroke. However, MAPC treatment also attenuated inflammatory response in the spleen and protected the spleen against stroke-related mass loss and cell death. These improvements also correlated to a decrease in pro-inflammatory cytokine levels and an increase in anti-inflammatory cytokine levels in splenocytes and blood and an elevation in immunosuppressive regulatory T cell levels in the spleen. Excitingly, the MAPC-induced anti-inflammatory activity also promoted functional recovery in stroke rats; however, the absence of a spleen entirely abrogated any neurological functional recovery associated with MAPC transplantation.

Together, these new findings suggest that systemic MAPC-treatment dampens pro-inflammatory responses from the spleen to create an environment conducive to a reparative response in the brain and recovery from stroke. Therefore, systemic MAPC treatment directly following stroke (as assessed in the previously mentioned trial [4]) could form part of an effective treatment for human patients.

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References

  1. Vendrame M, Gemma C, Pennypacker KR, et al. Cord blood rescues stroke-induced changes in splenocyte phenotype and function. Exp Neurol 2006;199:191-200.
  2. Seifert HA, Hall AA, Chapman CB, et al. A transient decrease in spleen size following stroke corresponds to splenocyte release into systemic circulation. J Neuroimmune Pharmacol 2012;7:1017-1024.
  3. Seifert HA, Leonardo CC, Hall AA, et al. The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling. Metabolic brain disease 2012;27:131-141.
  4. Hess DC, Sila CA, Furlan AJ, et al. A double-blind placebo-controlled clinical evaluation of MultiStem for the treatment of ischemic stroke. International journal of stroke : official journal of the International Stroke Society 2014;9:381-386.
  5. Yang B, Hamilton JA, Valenzuela KS, et al. Multipotent Adult Progenitor Cells Enhance Recovery After Stroke by Modulating the Immune Response from the Spleen. STEM CELLS 2017;35:1290-1302.