Post-stroke inflammation and the potential efficacy of novel stem cell therapies: focus on amnion epithelial cells

Abstract

Ischemic stroke is a debilitating disease for which there are currently no effective treatments besides the clot-buster, tissue plasminogen activator (t-PA), which is administered to less than 10% of patients due to a limited (4.5 h) time window of efficacy. Thus, there is an urgent need for novel therapies that can prevent or reverse the effects of stroke-induced brain injury. Recent encouraging reports have revealed that stem cells derived from human tissue, including embryonic, induced pluripotent, neural, and mesenchymal cells, can rescue injured brain tissue and improve functional recovery in experimental models of stroke. However, there are potentially major limitations to each of these types of stem cells that may ultimately prevent or restrict their use as viable mainstream treatment options for stroke patients. Conversely, stem cells derived from the placenta, such as human amnion epithelial cells (hAECs), appear to have several important advantages over other stem cell lineages, in particular their non-tumorigenic and non-immunogenic characteristics. Surprisingly, so far hAECs have received little attention as a potential stroke therapy. This brief review will firstly describe the inflammatory response and immune cell involvement following stroke, and then consider the potential for hAECs to improve stroke outcome given their unique characteristics. These actions of hAECs may involve a reduction of local inflammation and modulation of the immune response, promotion of neural recovery, differentiation into neural tissue, re-innervation of lost connections, and secretion of necessary cytokines, growth factors, hormones and/or neurotransmitters to restore cellular function.

Neuroinflammatory response to experimental stroke is inhibited by eriodictyol

“…The immune system plays an integral role in the pathogenesis of ischemic stroke and it contributes to infarct formation [10,64]. Leukocyte infiltration into the brain parenchyma is associated with the activation of microglia and astrocytes after brain ischemia, which contributes to the production of various pro-inflammatory mediators [65] and anti-inflammatory therapies have shown neuroprotective effects in animals subjected to pMCAO [66].…”

“…Anti-inflammatories constitute an important therapeutic strategy for stroke [2,9] because currently, the only available treatment to reduce brain damage after stroke is the "clot-buster," tissue plasminogen activator (t-PA). Thus, there is a great need to develop novel therapies for cerebrovascular diseases [10].…”

The Efficacy and Safety of Granulocyte Colony-Stimulating Factor for Patients with Stroke

“…With the growing aging population, the number of patients tormented with stroke may achieve a higher increase in the future. 2,3 As one of the main treatments, intravenous tissue plasminogen activator is the only Food and Drug Administration-approved thrombolytic agent currently available for acute ischemic stroke. 4 However, its narrow therapeutic time window makes it a limitation to apply in clinical practice.…”

Macrophages directed approaches are paramount for effective cancer immunotherapies

“…Like TAM, MSC also secrete various factors which are involved in wound healing (VEGF, HGF etc.) as well as in immune suppression (PEG2, IDO) [106,107] and correlate with cancer progression, development, recurrence and metastasis. MSC has been instrumental in promoting cancer stem cell function or promoting tumor associated macrophages (TAM) function in tumor microenvironment.…”