Extracellular Vesicles as a Potential Therapy for Neonatal Conditions: State of the Art and Challenges in Clinical Translation

Abstract

Despite advances in intensive care, several neonatal conditions typically due to prematurity affect vital organs and are associated with high mortality and long-term morbidities. Current treatment strategies for these babies are only partially successful or are effective only in selected patients. Regenerative medicine has been shown to be a promising option for these conditions at an experimental level, but still warrants further exploration for the development of optimal treatment. Although stem cell-based therapy has emerged as a treatment option, studies have shown that it is associated with potential risks and hazards, especially in the fragile population of babies. Recently, extracellular vesicles (EVs) have emerged as an attractive therapeutic alternative that holds great regenerative potential and is cell-free. EVs are nanosized particles endogenously produced by cells that mediate intercellular communication through the transfer of their cargo. Currently, EVs are garnering considerable attention as they are the key effectors of stem cell paracrine signaling and can epigenetically regulate target cell genes through the release of RNA species, such as microRNA. Herein, we review the emerging literature on the therapeutic potential of EVs derived from different sources for the treatment of neonatal conditions that affect the brain, retinas, spine, lungs, and intestines and discuss the challenges for the translation of EVs into clinical practice.

Small extracellular vesicles derived from embryonic stem cells restore ovarian function of premature ovarian failure through PI3K/AKT signaling pathway

“…Small EVs are defined as EVs with diameters that are less than 200 nm [7]. Accumulating evidence indicates that EVs hold a similar function to their parental cells in promoting tissue regeneration [8]. Meanwhile, they can avoid potential risks during the cell transplantation process, providing a safer substitution for therapeutic application in the clinic [9, 10].…”

Breast Milk Lipids and Fatty Acids in Regulating Neonatal Intestinal Development and Protecting against Intestinal Injury

“…Breast milk provides complex lipids through the delivery of MFGMs and exosomes. Published data support the role of extracellular vesicles on intestinal development and protection from intestinal injury such as NEC [112][113][114]. When evaluated in totality versus in individual components, human milk-derived exosomes attenuate oxidative stress-induced cell death in intestinal epithelial cells [115] and enhance proliferation and migration of intestinal epithelial cells in preterm infants compared to those with full term birth [116].…”

Umbilical cord-derived Wharton’s jelly for regenerative medicine applications

“…Exosomes are secreted from several cell types including stem cells and represent an important mode of intercellular communications [13]. Recently, exosomes have also emerged as an attractive cell-free therapeutic alternative that holds great regenerative potential [14].…”