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Amniotic Fluid Stem Cell-derived Exosomal MicroRNAs – A Safe and Effective Treatment for Stroke?

Review of "Neuroprotective effects of human amniotic fluid stem cells-derived secretome in an ischemia/reperfusion model" from STEM CELLS Translational Medicine by Stuart P. Atkinson

As we currently lack effective neuroprotective therapeutics for the cerebral ischemia/reperfusion (I/R) injury associated with ischemic stroke [1], researchers led by Annamaria Cimini (University of L'Aquila, L'Aquila) and Liborio Stuppia ("G. D'Annunzio" University, Chieti‐Pescara, Italy) recently sought to explore the paracrine acting factors secreted by amniotic fluid stem cells [2] as a potential treatment option. As reported in their recent STEM CELLS Translational Medicine study [3], Castelli et al. now describe the therapeutic relevance of amniotic fluid stem cell-derived exosomal microRNAs in the activation of pro‐survival and anti‐apoptotic pathways in a cell-based I/R-injury model system.

The authors assessed the therapeutic relevance of factors secreted from a previously described human amniotic fluid stem cell line [4] using a widely studied in vitro I/R model involving the use of differentiated SH‐SY5Y cells. The authors report a broad neuroprotective effect following the addition of amniotic fluid stem cell-conditioned medium to cells after I/R-injury, with the exosomal fraction of the conditioned medium noted to induce this effect to a similar level as the complete conditioned medium. Furthermore, both the amniotic fluid stem cell-conditioned medium and exosomal fraction contained high levels of the brain-derived neurotrophic factor (BDNF) neurotrophin.

Subsequent analysis of exosomal microRNAs highlighted the overexpression of 16 microRNAs that impacted pro‐survival and anti‐apoptotic pathways, such as by activating the BDNF/tropomyosin receptor kinase (TrkB) neurotrophic pathways, suppressing the p75 neurotrophin receptor (p75NTR)/c-Jun N-terminal kinase (JNK) death pathway, and further inducing the phosphatidylinositol‐3 kinase (PI3K)/protein kinase B (Akt) and extracellular signal-regulated kinase 5 (ERK5) survival pathways. Of the microRNAs of interest, seven have described roles in neuroprotection; however, others, which include miR‐221‐3p, miR‐222‐3p, miR‐24‐3p, and miR‐28‐5p, have limited or conflicting data regarding their function and implication in neuronal processes.

Overall, the authors believe that their findings support the use of amniotic fluid stem cell-derived exosomes as a safe and effective means to stimulate neuronal plasticity, ameliorate cognitive loss, and provide for neural replacement following stroke and I/R-injury in general.

For more on the therapeutic power of amniotic fluid stem cells, stem cell-derived exosomes, and microRNAs, stay tuned to the Stem Cells Portal!


  1. Yang Q, Huang Q, Hu Z, et al., Potential Neuroprotective Treatment of Stroke: Targeting Excitotoxicity, Oxidative Stress, and Inflammation. Frontiers in Neuroscience 2019;13:1036.
  2. Loukogeorgakis SP and De Coppi P, Concise Review: Amniotic Fluid Stem Cells: The Known, the Unknown, and Potential Regenerative Medicine Applications. STEM CELLS 2017;35:1663-1673.
  3. Castelli V, Antonucci I, d'Angelo M, et al., Neuroprotective effects of human amniotic fluid stem cells-derived secretome in an ischemia/reperfusion model. STEM CELLS Translational Medicine 2021;10:251-266.
  4. Pipino C, Pierdomenico L, Di Tomo P, et al., Molecular and Phenotypic Characterization of Human Amniotic Fluid-Derived Cells: A Morphological and Proteomic Approach. Stem Cells and Development 2015;24:1415-1428.