MicroRNA Mediated Cardioprotection – Is There a Path to Clinical Translation?

Nazari-Shafti, Timo Z.; Exarchos, Vasileios; Biefer, Héctor Rodriguez Cetina; Cesarovic, Nikola; Meýborg, Heike; Falk, Volkmar; Emmert, Maximilian Y.

doi:10.3389/fbioe.2020.00149

Cited by 10 publications

(6 citation statements)

References 88 publications

(113 reference statements)

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“…To date, more than 150 miRNAs have been identified in MSC-derived EVs [13]. Although there are some differences in the miRNA profile depending on the source of MSCs, a number of cardioprotective miRNAs have been identified that are commonly transported by EVs from various MSC tissue origins [14]. MiRNAs encapsulated in EVs have several functions including regulation of cell physiology, proliferation, cell differentiation, and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

MiRNA Profiles of Extracellular Vesicles Secreted by Mesenchymal Stromal Cells—Can They Predict Potential Off-Target Effects?

et al. 2020

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The cardioprotective properties of extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) are currently being investigated in preclinical studies. Although microRNAs (miRNAs) encapsulated in EVs have been identified as one component responsible for the cardioprotective effect of MSCs, their potential off-target effects have not been sufficiently characterized. In the present study, we aimed to investigate the miRNA profile of EVs isolated from MSCs that were derived from cord blood (CB) and adipose tissue (AT). The identified miRNAs were then compared to known targets from the literature to discover possible adverse effects prior to clinical use. Our data show that while many cardioprotective miRNAs such as miR-22-3p, miR-26a-5p, miR-29c-3p, and miR-125b-5p were present in CB- and AT-MSC-derived EVs, a large number of known oncogenic and tumor suppressor miRNAs such as miR-16-5p, miR-23a-3p, and miR-191-5p were also detected. These findings highlight the importance of quality assessment for therapeutically applied EV preparations.

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Section: Introductionmentioning

confidence: 99%

MiRNA Profiles of Extracellular Vesicles Secreted by Mesenchymal Stromal Cells—Can They Predict Potential Off-Target Effects?

et al. 2020

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“…Systems integration of a (cardio)vasculogenic secretome, arising from a distinct intracellular miRNA profile, distinguished cardiopoietic cells endowed with enhanced capacity. This is concordant with miRNA centrality in regulating regenerative and cardioprotective capacity 24,25 . Downregulation of miR‐146a‐5p or miR‐146b‐5p alters paracrine‐mediated immunomodulatory outcomes in cardiac signaling and facilitates repair postinfarction 26,27 .…”

Section: Discussionmentioning

confidence: 56%

“…This is concordant with miRNA centrality in regulating regenerative and cardioprotective capacity. 24,25 Downregulation of miR-146a-5p or miR-146b-5p alters paracrine-mediated immunomodulatory outcomes in cardiac signaling and facilitates repair postinfarction. 26,27 The present study supports the notion that secretome proficiency contributes to rescue of organ failure.…”

Section: Discussionmentioning

confidence: 99%

Secretome Signature of Cardiopoietic Cells Echoed in Rescued infarcted Heart Proteome

Arrell

Crespo‐Diaz

Yamada

et al. 2021

Stem Cells Translational Medicine

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Stem cell paracrine activity is implicated in cardiac repair. Linkage between secretome functionality and therapeutic outcome was here interrogated by systems analytics of biobanked human cardiopoietic cells, a regenerative biologic in advanced clinical trials. Protein chip array identified 155 proteins differentially secreted by cardiopoietic cells with clinical benefit, expanded into a 520 node network, collectively revealing inherent vasculogenic properties along with cardiac and smooth muscle differentiation and development. Next generation RNA sequencing, refined by pathway analysis, pinpointed miR-146 dependent regulation upstream of the decoded secretome. Intracellular and extracellular integration unmasked commonality across cardiovasculogenic processes. Mirroring the secretome pattern, infarcted hearts benefiting from cardiopoietic cell therapy restored the disease proteome engaging cardiovascular system functions. The cardiopoietic cell secretome thus confers a therapeutic molecular imprint on recipient hearts, with response informed by predictive systems profiling.

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“…Previously, the miRNA and lncRNA profiles of human derived ESC-CM-Exo and iPSC-CM-Exo harvested under hypoxic and normoxic conditions were found to be similar including the expression of cardioprotective miRs like mi-R1 , miR-21 , and miR-30 ( Lee et al, 2017 ). A q-PCR analysis showed the abundance of miR-21 and miR-210 in iPSC-Exo, known for their cardioprotective roles by targeting programmed cell death protein 4 and Ephrin-A3, inhibiting apoptosis and promoting angiogenesis ( Nazari-Shafti et al, 2020 ).…”

Section: Induced Pluripotent Stem Cell Exosomementioning

confidence: 99%

Nano-Messengers of the Heart: Promising Theranostic Candidates for Cardiovascular Maladies

Yedavilli

Singh

Singh³

et al. 2022

Front. Physiol.

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Till date, cardiovascular diseases remain a leading cause of morbidity and mortality across the globe. Several commonly used treatment methods are unable to offer safety from future complications and longevity to the patients. Therefore, better and more effective treatment measures are needed. A potential cutting-edge technology comprises stem cell-derived exosomes. These nanobodies secreted by cells are intended to transfer molecular cargo to other cells for the establishment of intercellular communication and homeostasis. They carry DNA, RNA, lipids, and proteins; many of these molecules are of diagnostic and therapeutic potential. Several stem cell exosomal derivatives have been found to mimic the cardioprotective attributes of their parent stem cells, thus holding the potential to act analogous to stem cell therapies. Their translational value remains high as they have minimal immunogenicity, toxicity, and teratogenicity. The current review highlights the potential of various stem cell exosomes in cardiac repair, emphasizing the recent advancements made in the development of cell-free therapeutics, particularly as biomarkers and as carriers of therapeutic molecules. With the use of genetic engineering and biomimetics, the field of exosome research for heart treatment is expected to solve various theranostic requirements in the field paving its way to the clinics.

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MicroRNA Mediated Cardioprotection – Is There a Path to Clinical Translation?

Cited by 10 publications

References 88 publications

MiRNA Profiles of Extracellular Vesicles Secreted by Mesenchymal Stromal Cells—Can They Predict Potential Off-Target Effects?

MiRNA Profiles of Extracellular Vesicles Secreted by Mesenchymal Stromal Cells—Can They Predict Potential Off-Target Effects?

Secretome Signature of Cardiopoietic Cells Echoed in Rescued infarcted Heart Proteome

Nano-Messengers of the Heart: Promising Theranostic Candidates for Cardiovascular Maladies

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