Endothelial Progenitor Cells Modulate Inflammation-Associated Stroke Vasculome

Abstract

Stroke remains a major unmet clinical need that warrants novel therapies. Following an ischemic insult, the cerebral vasculature secretes inflammatory molecules, creating the stroke vasculome profile. The present study evaluated the therapeutic effects of endothelial cells on the inflammation-associated stroke vasculome. qRT-PCR analysis revealed that specific inflammation-related vasculome genes BRM, IκB, Foxf1, and ITIH-5 significantly upregulated by oxygen glucose deprivation (OGD. Interestingly, co-culture of human endothelial cells (HEN6) with human endothelial cells (EPCs) during OGD significantly blocked the elevations of BRM, IκB, and Foxf1, but not ITIH-5. Next, employing the knockdown/antisense technology, silencing the inflammation-associated stroke vasculome gene, IκB, as opposed to scrambled knockdown, blocked the EPC-mediated protection of HEN6 against OGD. In vivo, stroke animals transplanted with intracerebral human EPCs (300,000 cells) into the striatum and cortex 4 h post ischemic stroke displayed significant behavioral recovery up to 30 days post-transplantation compared to vehicle-treated stroke animals. At 7 days post-transplantation, quantification of the fluorescent staining intensity in the cortex and striatum revealed significant upregulation of the endothelial marker RECA1 and a downregulation of the stroke-associated vasculome BRM, IKB, Foxf1, ITIH-5 and PMCA2 in the ipsilateral side of cortex and striatum of EPC-transplanted stroke animals relative to vehicle-treated stroke animals. Altogether, these results demonstrate that EPCs exert therapeutic effects in experimental stroke possibly by modulating the inflammation-plagued vasculome.

A Gutsy Move for Cell-Based Regenerative Medicine in Parkinson’s Disease: Targeting the Gut Microbiome to Sequester Inflammation and Neurotoxicity

“…Finally, because CBP has been shown to be an effective human primary cell culture supplement, exchanging CBP for standard cord blood stem cell transplant diluents may improve stem cell survival by creating a more viable microenvironment, which may improve the overall effectiveness of the cell infusions [38–41]. To further advance the translation of hUCB+P therapy for clinical applications, future studies should examine the timing, dose, and route of delivery (e.g., direct injections into the gut) that will optimally sequester inflammation and reduce neurotoxicity [73, 74], altogether retarding the disease progression.…”

Characterization and Functional Assessment of Endothelial Progenitor Cells in Ischemic Stroke Patients

“…An important aspect of EPC functionality is their paracrine action. Stem cells have been shown to be capable of releasing of soluble biofactors (SBF) that have immunomodulatory, anti-inflammatory, tissue protective and regenerative effects [ 57 ], and the paracrine function of EPCs plays a crucial role in the post-stroke phase [ 58 , 59 ]. The decreased capability, or even inability, of secreting SBF would dramatically affect EPC performance and thus resulted in decreased or absent angiogenesis and vascular repair.…”

ATP-Nlrp3 Inflammasome-Complement Cascade Axis in Sterile Brain Inflammation in Psychiatric Patients and its Impact on Stem Cell Trafficking

“…This process is also tightly controlled by the anti-inflammatory and Nlrp3-inhibitory action of HO-1 and iNOS [47,48]. In parallel, during ComC activation subsets of stem cells from bone marrow are mobilized into peripheral blood that may be involved in certain brainremodeling processes [16,49] or exert ani-inflammatory effects [50,51]. All these observations suggest that modulating innate immune responses related to sterile inflammation will enable the development of the novel innovative approaches for the treatment of psychiatric disorders targeting ATP-Nlrp3 inflammasome-ComC axis.…”