Therapeutic potential of extracellular vesicles derived from human amniotic epithelial cells for perinatal cerebral and pulmonary injury

Abstract

Lung and brain injury that occurs during the perinatal period leads to lifelong disability and is often driven and/or exacerbated by inflammation. Human amniotic epithelial cells (hAEC), which demonstrate immunomodulatory, anti-fibrotic, and regenerative capabilities, are being explored as a therapeutic candidate for perinatal injury. However, limitations regarding scalable manufacturing, storage, transport, and dose-related toxicity have impeded clinical translation. Isolated therapeutic extracellular vesicles (EVs) from stem and stem-like cells are thought to be key paracrine mediators of therapeutic efficacy. The unique characteristics of EVs suggest that they potentially circumvent the limitations of traditional cell-based therapies. However, given the novelty of EVs as a therapeutic, recommendations around ideal methods of production, isolation, storage, and delivery have not yet been created by regulatory agencies. In this concise review, we discuss the pertinence and limitations of cell-based therapeutics in perinatal medicine. We also review the preclinical evidence supporting the use of therapeutic EVs for perinatal therapy. Further, we summarize the arising considerations regarding adequate cell source, biodistribution, isolation and storage methods, and regulatory roadblocks for the development of therapeutic EVs.

Keywords: brain; extracellular vesicles; human amniotic epithelial cells; lung; perinatal injury.

Graphical Abstract

Figure 1.

Current EV therapeutics tested in preclinical in vivo models of neonatal cerebral and pulmonary injury. Abbreviations: BM-MSC, bone marrow derived mesenchymal stromal cells; UC-MSC, umbilical cord derived mesenchymal stromal cells; WJ-MSC, Wharton’s jelly derived mesenchymal stromal cells; NSC, neural stem cell; AD-MSC, adipose derived mesenchymal stromal cells; HBM, human breast milk. Created with BioRender.com.