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.
Highlights
According to the World Health Organization, one of the leading causes of pediatric mortality globally is prematurity [1]
To prove that the Annexin A1 contained in extracellular vesicles (EVs) played a key role, the authors administered purified human Annexin A1 or bone marrow-derived mesenchymal stem cells (BM-MSCs) EVs and confirmed that both improved blood–brain barrier (BBB) integrity, which in turn was abolished by the Annexin A1 receptor blocker, the formyl peptide receptor inhibitor [33]. These findings suggest the delivery of Annexin A1 via EVs maintains BBB integrity in the immature brain following hypoxic ischemic brain injury
Both exosomes and miR-24-3p inhibited the inositol-requiring enzyme 1a (IRE1a)-X-box binding protein 1 (XBP1) pathway, which plays a role in endoplasmic reticulum stress-mediated hypoxia-induced photoreceptor apoptosis [44]
Summary
According to the World Health Organization, one of the leading causes of pediatric mortality globally is prematurity [1]. Disorders of premature babies that require medical treatment commonly affect the central nervous system, the cardiorespiratory system, and the gastrointestinal tract These include conditions such as intraventricular hemorrhage (IVH), cerebral palsy, bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC) [3]. Recognized risk factors and hazards associated with stem cell-based therapy include rejection, toxicity, unwanted biological effects, tumorigenic potential, and contamination by adventitious agents [9]. To overcome these challenges, researchers have investigated whether stem cell derivatives could hold the same regenerative potential as their parent cells without the mentioned associated risks and whether they could be used as alternative therapeutic agents for neonatal conditions. We discuss the challenges related to the translation of EVs as therapeutics into clinical practice for this fragile population of patients
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