miRNA-Guided Regulation of Mesenchymal Stem Cells Derived from the Umbilical Cord: Paving the Way for Stem-Cell Based Regeneration and Therapy

Abstract

The human body is an abundant source of multipotent cells primed with unique properties that can be exploited in a multitude of applications and interventions. Mesenchymal stem cells (MSCs) represent a heterogenous population of undifferentiated cells programmed to self-renew and, depending on their origin, differentiate into distinct lineages. Alongside their proven ability to transmigrate toward inflammation sites, the secretion of various factors that participate in tissue regeneration and their immunoregulatory function render MSCs attractive candidates for use in the cytotherapy of a wide spectrum of diseases and conditions, as well as in different aspects of regenerative medicine. In particular, MSCs that can be found in fetal, perinatal, or neonatal tissues possess additional capabilities, including predominant proliferation potential, increased responsiveness to environmental stimuli, and hypoimmunogenicity. Since microRNA (miRNA)-guided gene regulation governs multiple cellular functions, miRNAs are increasingly being studied in the context of driving the differentiation process of MSCs. In the present review, we explore the mechanisms of miRNA-directed differentiation of MSCs, with a special focus on umbilical cord-derived mesenchymal stem cells (UCMSCs), and we identify the most relevant miRNAs and miRNA sets and signatures. Overall, we discuss the potent exploitations of miRNA-driven multi-lineage differentiation and regulation of UCMSCs in regenerative and therapeutic protocols against a range of diseases and/or injuries that will achieve a meaningful clinical impact through maximizing treatment success rates, while lacking severe adverse events.

The role of microRNAs in axon regeneration after peripheral nerve injury: a bibliometric analysis

“…A recent study has shown that miRNAs can regulate the proliferation, differentiation, and immunoregulatory functions of MSCs ( 24 ). By regulating the expression levels of miRNAs, the biological characteristics of MSCs can be affected, further influencing their potential for tissue repair and regeneration ( 25 ). Additionally, MSCs themselves can release extracellular vesicles rich in miRNAs, and miRNAs delivered by these vesicles can affect the gene expression and function of surrounding cells ( 26 ).…”

“…The collected literature data, after being visualized and mapped using CiteSpace 6.4.2R and VOSviewer 1.6.19, can greatly assist authors in analysis and research. Web of Science is a data services platform provided by Clarivate Analytics, as the largest and most comprehensive academic resource library in the world, covering biomedical, engineering, natural science, social science, humanities, and arts, with more than 8,700 core journals, regarded as the data source platform by this study ( 25 ). It also includes information on cited references, authors, sources, and publication years.…”

Mimic miRNA and Anti-miRNA Activated Scaffolds as a Therapeutic Strategy to Promote Bone, Cartilage, and Skin Regeneration

“…To date, miRNA-activated scaffolds, administered via MSCs or directly cell-free, for tissue repair are gaining increasing interest, with studies targeting bone, liver, cardiac, cartilage, neurons, epithelia, and other tissues [105]. The following section of this review provides an overview of the principal miRNA-activated scaffold strategies used in bone, cartilage, and skin regeneration (Table 2).…”

Applications of Stem Cell-Derived Extracellular Vesicles in Nerve Regeneration

“…EVs consist of lipids, nucleic acids, proteins such as transmembrane and cytosolic proteins, and proteins involved with lipid metabolism. They are defined as lipid-bound vesicles excreted by cells into the extracellular space [ 7 , 8 , 9 , 10 , 11 , 12 ]. In general, a simple classification has been made according to release mechanisms and dimensions, but this classification is still not fully clarified.…”