Amniotic fluid-derived extracellular vesicles: characterization and therapeutic efficacy in an experimental model of bronchopulmonary dysplasia.

BACKGROUND AIMS: Extracellular vesicles (EVs) are being tested for their use as novel therapeutics. However, the optimal source of EVs is currently under investigation. Amniotic fluid (AF) is a natural source of EVs that can be easily obtained for use in regenerative medicine, yet AF-EV characterization has not been fully explored. METHODS: Here the authors demonstrate AF as a rich source of EVs and identify the microRNA and proteomic cargo. Bioinformatics analysis of this cargo revealed multiple pathway targets, including immunomodulatory, anti-inflammatory and free radical scavenging networks. The authors further demonstrated the therapeutic potential of this EV product as a novel preventative agent for bronchopulmonary dysplasia (BPD). RESULTS: Intra-tracheal administration of AF-EVs preserved alveolar development, attenuated vascular remodeling and pulmonary hypertension, decreased lung pro-inflammatory cytokine expression and reduced macrophage infiltration in an experimental BPD model. CONCLUSIONS: The authors' results suggest that AF is a viable biological fluid for EV harvest and that AF-EVs have strong therapeutic potential for pulmonary diseases, such as BPD, warranting further development to transition this novel EV product into the clinic.

Treatment of a COVID-19 long hauler with an amniotic fluid-derived extracellular vesicle biologic.

Post-COVID-19 infection symptoms such as mental fog, tachycardia, and extreme fatigue are just a few of the symptoms wreaking havoc on patients' lives. Patients with long-term symptoms following COVID-19 are being called long haulers. To date, long haulers are receiving little to no guidance from physicians on their lingering COVID-19 symptoms with limited treatment options available. Zofin is an acellular biologic that contains the extracellular vesicle (EV) fraction of human amniotic fluid and is under investigation for use as a COVID-19 therapeutic. We obtained FDA and IRB approval to investigate the therapeutic use of Zofin in a single long hauler patient case experiencing prolonged shortness of breath and respiratory impairment. Administration of the EV product was shown to be safe. Furthermore, demonstrated respiratory improvements through chest X ray images and oxygen saturation measurement. The single patient IND studies were completed without any reported adverse events or safety concerns. Furthermore, these completed studies demonstrate the feasibility and a therapeutic potential of amniotic fluid-derived EVs for COVID-19 long hauler intervention.

Case Report: Administration of Amniotic Fluid-Derived Nanoparticles in Three Severely Ill COVID-19 Patients.

Rationale/Objectives: A human coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak worldwide. There is an urgent need to develop new interventions to suppress the excessive immune response, protect alveolar function, and repair lung and systemic organ damage. Zofin (previously known as Organicell Flow) is a novel therapeutic that is derived from the soluble and nanoparticle fraction (extracellular vesicles and exosomes) of human amniotic fluid. Here within, we present the clinical outcomes after Zofin treatment in three critically ill patients suffering from severe, multi-organ complications induced by COVID-19 infection. All patients were diagnosed with COVID-19, developed respiratory failure, and were hospitalized for more than 40 days. Methods: Zofin was administered to patients concurrently with ongoing medical care who were monitored for 28-days post-therapy. SOFA score assessment, chest X-rays, and inflammatory biomarker testing was performed. Main Results: There were no adverse events associated with the therapy. The patients showed improvements in ICU clinical status and experienced respiratory improvements. Acute delirium experienced by patients completely resolved and inflammatory biomarkers improved. Conclusions: Primary outcomes demonstrate the therapy was safe, accessible, and feasible. This is the first demonstration of human amniotic fluid-derived nanoparticles as a safe and potentially efficacious therapeutic treatment for respiratory failure induced by COVID-19 infection.