Secretome of Stressed Peripheral Blood Mononuclear Cells Alters Transcriptome Signature in Heart, Liver, and Spleen after an Experimental Acute Myocardial Infarction: An In Silico Analysis

Abstract

Acute myocardial infarction (AMI) is a result of cardiac non-perfusion and leads to cardiomyocyte necrosis, inflammation, and compromised cardiac performance. Here, we showed that the secretome of γ-irradiated peripheral blood mononuclear cells (PBMCsec) improved heart function in a porcine AMI model and displayed beneficial long- and short-term effects. As an AMI is known to strongly affect gene regulation of the ischemia non-affected heart muscle and distal organs, we employed a transcriptomics approach to further study the immediate molecular events orchestrated using the PBMCsec in myocardium, liver, and spleen 24 h post ischemia. In the infarcted area, the PBMCsec mainly induced genes that were essential for cardiomyocyte function and simultaneously downregulated pro-inflammatory genes. Interestingly, genes associated with pro-inflammatory processes were activated in the transition zone, while being downregulated in the remote zone. In the liver, we observed a pronounced inhibition of immune responses using the PBMCsec, while genes involved in urea and tricarboxylic cycles were induced. The spleen displayed elevated lipid metabolism and reduced immunological processes. Together, our study suggested several types of pharmacodynamics by which the PBMCsec conferred immediate cardioprotection. Furthermore, our data supported the assumption that an AMI significantly affects distal organs, suggesting that a holistic treatment of an AMI, as achieved by PBMCsec, might be highly beneficial.

Impact of peripheral blood mononuclear cells preconditioned by activated platelet supernatant in managing gastric mucosal damage induced by zinc oxide nanoparticles in rats

“…The therapeutic efficacy of the PBMC in ZON-induced gastric injury may be also attributed to the anti-inflammatory and immunomodulatory action of their biological paracrine secretomes such as non-oxidized lipids, proteins and extracellular vesicles. These secretomes can suppress the elevated TNF-α, NF-ĸB, and COX-2 alleviating gastric mucosal inflammation and promoting mucosal regeneration [ 72 - 74 ]. Also, PBMC could modulate the anti-oxidant markers, diminish apoptosis and increase epithelial cell proliferation helping in gastric mucosal healing [ 66 ].…”

Clinical Pharmacology Superlymph in Diseases of the Urogenital Tract Through the Prism of the Levels of Implementation of Its Effects

“…[65]. Фармакологические знания расширяются благодаря использованию современных научных методов, подтверждающих, что секретом мононуклеаров периферической крови изменяет сигнатуру транскриптома в сердце, печени и селезенке после экспериментального острого инфаркта миокарда [66], ослабляет активацию тучных клеток и базофилов [67], активирует проангиогенные и антипротеолитические процессы в клетках цельной крови и защищает эндотелиальный барьер [68], подавляет образование нейтрофильных внеклеточных ловушек [69], ослабляет гипертрофическое рубцевание кожи [70].…”

The Effect of Paracrine Factors Released by Irradiated Peripheral Blood Mononuclear Cells on Neutrophil Extracellular Trap Formation

“…Recent advances in cell-derived, yet cell-free medicinal products have increasingly gained attention in regenerative medicine [ 27 , 28 ]. Although initial research on cell-free therapeutic agents focused on secretomes derived from stem cells, we could demonstrate that the secretome of peripheral blood mononuclear cells (PBMC) exhibits comparable regenerative effects [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. The potency of the PBMC-derived secretome (PBMCsec) was further increased by exposing PBMCs to 60 Gy γ-irradiation, which induces apoptosis and necroptosis, resulting in the release of a plethora of pro-regenerative paracrine factors [ 29 ].…”