Therapeutic potential of extracellular vesicles derived from human amniotic epithelial cells for perinatal cerebral and pulmonary injury. DOI Creative Commons
Naveen Kumar, Hamid Reza Bidkhori, Tamara Yawno

et al.

Stem Cells Translational Medicine, Journal Year: 2024, Volume and Issue: 13(8), P. 711 - 723

Published: June 19, 2024

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

Language: Английский

Amniotic fluid stem cell extracellular vesicles as a novel fetal therapy for pulmonary hypoplasia: a review on mechanisms and translational potential DOI Creative Commons
Fabian Doktor, Lina Antounians, Rebeca Lopes Figueira

et al.

Stem Cells Translational Medicine, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 1, 2025

Disruption of developmental processes affecting the fetal lung leads to pulmonary hypoplasia. Pulmonary hypoplasia results from several conditions including congenital diaphragmatic hernia (CDH) and oligohydramnios. Both entities have high morbidity mortality, no effective therapy that fully restores normal development. Hypoplastic lungs impaired growth (arrested branching morphogenesis), maturation (decreased epithelial/mesenchymal differentiation), vascularization (endothelial dysfunction vascular remodeling leading postnatal hypertension). Herein, we discuss pathogenesis role microRNAs (miRNAs) during pathological Since multiple cells pathways are altered, ideal strategy for hypoplastic is deliver a addresses all aspects abnormal In this review, report on novel regenerative approach based administration extracellular vesicles derived amniotic fluid stem (AFSC-EVs). Specifically, describe effects AFSC-EVs in rodent human models hypoplasia, their mechanism action via release cargo, miRNAs, anti-inflammatory properties. We also compare cargo contents EVs AFSCs mesenchymal stromal (MSCs). Overall, there compelling evidence antenatal rescues features development experimental Lastly, steps need be taken translate promising EV-based bench bedside. These include strategies overcome barriers commonly associated with EV therapeutics specific challenges related cell-based therapies medicine.

Language: Английский

Citations

2
Fetal hypoplastic lungs have multilineage inflammation that is reversed by amniotic fluid stem cell extracellular vesicle treatment DOI Creative Commons
Lina Antounians, Rebeca Lopes Figueira,

Bharti Kukreja

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(30)

Published: July 26, 2024

Antenatal administration of extracellular vesicles from amniotic fluid stem cells (AFSC-EVs) reverses features pulmonary hypoplasia in models congenital diaphragmatic hernia (CDH). However, it remains unknown which lung cellular compartments and biological pathways are affected by AFSC-EV therapy. Herein, we conducted single-nucleus RNA sequencing (snRNA-seq) on rat fetal CDH lungs treated with vehicle or AFSC-EVs. We identified that intra-amniotically injected AFSC-EVs reach the rats CDH, where they promote branching morphogenesis epithelial cell differentiation. Moreover, snRNA-seq revealed have a multilineage inflammatory signature macrophage enrichment, is reversed treatment. Macrophage enrichment was confirmed immunofluorescence, flow cytometry, inhibition studies GW2580. validated human autopsy samples. Together, this study advances knowledge pathogenesis further evidence value an EV-based therapy for fetuses.

Language: Английский

Citations

6
Antenatal Administration of Extracellular Vesicles Derived From Amniotic Fluid Stem Cells Improves Lung Function in Neonatal Rats With Congenital Diaphragmatic Hernia DOI
Rebeca Lopes Figueira,

Naghmeh Khoshgoo,

Fabian Doktor

et al.

Journal of Pediatric Surgery, Journal Year: 2024, Volume and Issue: 59(9), P. 1771 - 1777

Published: Feb. 28, 2024

Language: Английский

Citations

5
Amniotic fluid stem cell extracellular vesicles promote lung development via TGF-beta modulation in a fetal rat model of oligohydramnios DOI
Fabian Doktor, Rebeca Lopes Figueira,

Victoria Fortuna

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 377, P. 427 - 441

Published: Nov. 26, 2024

Language: Английский

Citations

5
Cellular origins and translational approaches to congenital diaphragmatic hernia DOI Creative Commons
Marietta Jank, Fabian Doktor, Augusto Zani

et al.

Seminars in Pediatric Surgery, Journal Year: 2024, Volume and Issue: 33(4), P. 151444 - 151444

Published: July 2, 2024

Congenital Diaphragmatic Hernia (CDH) is a complex developmental abnormality characterized by abnormal lung development, diaphragmatic defect and cardiac dysfunction. Despite significant advances in management of CDH, mortality morbidity continue to be driven pulmonary hypoplasia, hypertension, The etiology CDH remains unknown, but presumed caused combination genetic susceptibility external/environmental factors. Current research employs multi-omics technologies investigate the molecular profile pathways inherent CDH. aim discover underlying pathogenesis, new biomarkers ultimately novel therapeutic targets. Stem cells their cargo, non-coding RNAs agents targeting inflammation vascular remodeling have produced promising results preclinical studies using animal models Shortcomings current therapies combined with an improved understanding pathogenesis given rise experimental treatments that are currently being evaluated clinical trials. This review provides insight into developments translational research, ranging from cellular origins cardiopulmonary development identification treatment targets at bench translation trials bedside.

Language: Английский

Citations

4
Sex-specific differences in the severity of pulmonary hypoplasia in experimental congenital diaphragmatic hernia and implications for extracellular vesicle-based therapy DOI
Fabian Doktor, Emily Lo,

Victoria Fortuna

et al.

Pediatric Surgery International, Journal Year: 2024, Volume and Issue: 40(1)

Published: Oct. 28, 2024

Language: Английский

Citations

3
Amniotic fluid stem cell extracellular vesicles promote lung development via TGF-beta modulation in a fetal rat model of oligohydramnios DOI Open Access
Fabian Doktor, Rebeca Lopes Figueira,

Victoria Fortuna

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 22, 2024

Abstract Oligohydramnios (decreased amniotic fluid volume for gestational age) is a severe condition associated with high morbidity and mortality mainly due to fetal pulmonary hypoplasia. Currently, there are limited treatment options promote lung development. Administration of stem cells their derivates have shown promising regenerative properties several neonatal diseases related arrested Herein, we first characterized hypoplasia secondary oligohydramnios in surgical rat model. Experimental induction led impaired growth, branching morphogenesis (fewer airspaces decreased Fgf10 , Nrp1 Ctnnb1 expression), proximal/distal progenitor cell patterning Sox2 Sox9 TGF-β signaling. We then tested antenatal administration extracellular vesicles derived from (AFSC- EVs). In lungs, AFSC-EV improved airway at least part through the release miR-93-5p. Our experiments suggest that miR-93-5p blocked SMAD 7, resulting upregulation pSMAD2/3 restoration Conversely, lungs treated antagomir 93-5p transfected AFSC- EVs had This study reporting derivatives could be potential therapy rescue development fetuses oligohydramnios. Highlights Pulmonary rats by improves patterning. effects mediated via modulation signaling AFSC-EVs.

Language: Английский

Citations

1
Therapeutic potential of extracellular vesicles derived from human amniotic epithelial cells for perinatal cerebral and pulmonary injury. DOI Creative Commons
Naveen Kumar, Hamid Reza Bidkhori, Tamara Yawno

et al.

Stem Cells Translational Medicine, Journal Year: 2024, Volume and Issue: 13(8), P. 711 - 723

Published: June 19, 2024

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

Language: Английский

Citations

1