Human amniotic fluid stem cells protect rat lungs exposed to moderate hyperoxia

Grisafi, Davide; Pozzobon, Michela; Dedja, Arben; Vanzo, Valentina; Tomanin, Rosella; Porzionato, Andrea; Macchi, Veronica; Salmaso, Roberto; Scarpa, Maurizio; Cozzi, Emanuele; Fassina, Ambrogio; Navaglia, Filippo; Maran, Claudio; Onisto, Maurizio; Caenazzo, Luciana; Coppi, Paolo De; De, Raffaele; Chiandetti, Lino; Zaramella, Patrizia

doi:10.1002/ppul.22791

Cited by 51 publications

(48 citation statements)

References 49 publications

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“…However, in this study, we found that in the late phase of BPD, a single dose of EPCs administered through the peripheral venous route only increased lung microvessels, with no improvement in alveolar structure as determined by RAC measurements. Compared with the two previous studies (9,10), the reason why mono-EPCs treatment did not result in any improvement in alveolar structure could be due to the selected route of administration.…”

Section: Combined Epc Transplantation and Ino Improved Lung Structurementioning

confidence: 74%

“…Balasubramaniam et al (9) showed that bone marrow-derived angiogenic cells injected into the pulmonary circulation can restore lung alveolar and vascular structure after neonatal hyperoxia in infant mice. Grisafi et al (10) showed that amniotic fluid stem cells delivered intratracheally can restore partly alveolarization and angiogenesis in an adult rat model of hyperoxia lung injury. Although stem cell therapy is a promising novel therapy for vascular injury-related diseases, studies have demonstrated that only a small portion of transplanted cells can home to the target (11,12).…”

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confidence: 99%

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Combined iNO and endothelial progenitor cells improve lung alveolar and vascular structure in neonatal rats exposed to prolonged hyperoxia

Sun

Qian

2015

Pediatr Res

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Background: Stem cells or inhaled nitric oxide (iNO) are reported to improve lung structures in bronchopulmonary dysplasia (BPD) models. We hypothesized that combined iNO and transplanted endothelial progenitor cells (EPCs) might restore lung structure in rats after neonatal hyperoxia. Methods: Litters were separated into eight groups: room air, hyperoxia, hyperoxia + iNO, hyperoxia + iNO + L-NAME, hyperoxia + EPCs, hyperoxia + EPCs + L-NAME, hyperoxia + EPCs + iNO, and hyperoxia + EPCs + iNO + L-NAME. Litters were exposed to hyperoxia from the 21st day, then, sacrificed. EPCs were injected on the 21st day. L-NAME was injected daily for 7 d from the 21st day. Serum vascular endothelial growth factor (VEGF), radial alveolar count (RAC), VIII factor, EPCs engraftment, lung VEGF, VEGFR2, endothelial nitric oxide (eNOS) and SDF-1 expression, and NO production were examined. results: Hyperoxia exposure led to air space enlargement, loss of lung capillaries, and low expression of VEGF and eNOS. Transplanted EPCs, when combined with iNO, had significantly increased engraftment in lungs, compared to EPCs alone, upon hyperoxia exposure. There was improvement in alveolarization, microvessel density, and upregulation of VEGF and eNOS proteins in the hyperoxia-exposed EPCs with iNO group, compared to hyperoxia alone. conclusion: Combined EPCs and iNO improved lung structures after neonatal hyperoxia. This was associated with the upregulation of VEGF and eNOS expression.B ronchopulmonary dysplasia (BPD) is a chronic lung disease associated with significant mortality and morbidity in premature infants. New BPD is characterized by arrested alveolar and vascular growth (vascular hypothesis of BPD) (1,2). Alveolar formation is a highly coordinated process between the development of airways and pulmonary vasculature (3). Exposure to inflammation caused by excessive O 2 supplementation is hypothesized to interfere with the coordinated process of normal human lung development. Neonatal hyperoxia exposure is known to disrupt alveolar formation and growth, providing a useful model for studying BPD (4).Cell-based therapy is a novel approach that offers much promise in the prevention and treatment of BPD, including embryonic stem cells, mesenchymal stem cells, placental stem cells, umbilical cord stem cells, amniotic fluid and amnionderived cells, and lung progenitor cells. Endothelial progenitor cells (EPCs) are precursors of endothelial cells, which have the capacity of self-renewal and proliferation. EPCs is one of the key cells mediating vascular growth, which can mobilize from bone marrow and home to the site of vascular injuries, promoting neovascularization (5). There is data showing that reduced numbers or dysfunction of EPCs at birth is associated with the development of BPD (6,7). In addition, a reduction in the number of EPCs in the bone marrow, circulation and lungs has also emerged in animal models of BPD (8). Evidences that angiogenic cells treatment can restore lung structure have been demonstrated. Balasubramaniam et al...

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Section: Combined Epc Transplantation and Ino Improved Lung Structurementioning

confidence: 74%

mentioning

confidence: 99%

Combined iNO and endothelial progenitor cells improve lung alveolar and vascular structure in neonatal rats exposed to prolonged hyperoxia

Sun

Qian

2015

Pediatr Res

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“…Following implantation in rat and porcine animal models, there was partial replacement of gut function. 26,27,61,62 Even though there have been a number of studies studying the components, electrophysiology, immunology, angiogenesis and lymphangiogenesis of the TESI (for an overview of these, refer to Table 1 of Ref. 63), this methodology has been heavily criticised.…”

Section: Oesophagusmentioning

confidence: 98%

“…25 It is possible that AFS cells display a reparative potential through active involvement of cells in alveolarisation and angiogenesis in a rat model of hyperoxia. 26 Paracrine activity and direct contribution of the stem cells could become relevant in the near future and avoid the need of transplantation in severe CDH.…”

Section: Airwaysmentioning

confidence: 99%

Organ bioengineering for the newborn

Maghsoudlou

Urbani

Coppi

2014

Seminars in Pediatric Surgery

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“…Yet there has been no systematic review to assess the extent of current evidence regarding safety and efficacy of cell-based therapies in preclinical BPD and identify gaps that could jeopardize successful clinical translation. studies), [26][27][28][29]32,34,35,37,39,40,42,43,48,49,[51][52][53][55][56][57][58][59][61][62][63]66,[68][69][70]72,73,[75][76][77][78] human amniotic epithelial cells (hAEC, n = 4), 36,64,65,74 mononuclear CD34 + (n = 4), 27,30,46,47 endothelial colony forming cells (ECFC, n = 3), 46,64,70 endothelial progenitor cells (EPCs, n = 3), 31,41,71 bone marrow derived angiogenic cells (BMDAC, n = 1), 71 bone marrow derived (BM) ckit+ cells (n = 1), 50 cord blood CD34 + (n = 1), 44 human amniotic fluid stem cells (hAFSC, n = 1), 33 human-induced pluripotent...…”

Section: Significance Statementmentioning

confidence: 99%

Are all stem cells equal? Systematic review, evidence map, and meta-analyses of preclinical stem cell-based therapies for bronchopulmonary dysplasia

Augustine

Cheng

Chan

et al. 2019

Stem Cells Translational Medicine

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Regenerative stem cell-based therapies for bronchopulmonary dysplasia (BPD), the most common preterm birth complication, demonstrate promise in animals. Failure to objectively appraise available preclinical data and identify knowledge gaps could jeopardize clinical translation. We performed a systematic review and network metaanalysis (NMA) of preclinical studies testing cell-based therapies in experimental neonatal lung injury. Fifty-three studies assessing 15 different cell-based therapies were identified: 35 studied the effects of mesenchymal stromal cells (MSCs) almost exclusively in hyperoxic rodent models of BPD. Exploratory NMAs, for select outcomes, suggest that MSCs are the most effective therapy. Although a broad range of promising cell-based therapies has been assessed, few head-to-head comparisons and unclear risk of bias exists. Successful clinical translation of cell-based therapies demands robust preclinical experimental design with appropriately blinded, randomized, and statistically powered studies, based on biological plausibility for a given cell product, in standardized models and endpoints with transparent reporting. K E Y W O R D Sanimal model, bronchopulmonary dysplasia, cell-based therapy, lung injury, network metaanalysis, preclinical, preterm birth, stem cells, systematic review, translation

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Human amniotic fluid stem cells protect rat lungs exposed to moderate hyperoxia

Abstract: Treatment with hAFS cells has a reparative potential through active involvement of cells in alveolarization and angiogenesis. A downstream paracrine action was also taken into account, in order to understand the immunodulatory response.

Cited by 51 publications

References 49 publications

Combined iNO and endothelial progenitor cells improve lung alveolar and vascular structure in neonatal rats exposed to prolonged hyperoxia

Combined iNO and endothelial progenitor cells improve lung alveolar and vascular structure in neonatal rats exposed to prolonged hyperoxia

Organ bioengineering for the newborn

Are all stem cells equal? Systematic review, evidence map, and meta-analyses of preclinical stem cell-based therapies for bronchopulmonary dysplasia

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