Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia

Pierro, Maria; Ionescu, Lavinia; Montemurro, Tiziana; Vadivel, Arul; Weissmann, Gaia; Oudit, Gavin Y.; Emery, Derek; Bodiga, Sreedhar; Eaton, Farah; Péault, Bruno; Mosca, Fabio; Lazzari, Lorenza; Thébaud, Bernard

doi:10.1136/thoraxjnl-2012-202323

Cited by 222 publications

(240 citation statements)

References 35 publications

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“…Therefore, a long‐term follow‐up safety assessment is necessary to prove the safety of MSC transplantation 41, 42, 43. Such an assessment of the nine preterm infants treated with MSCs in this study is currently underway (NCT02673788).…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial

Ahn

Chang

Sung

et al. 2018

Stem Cells Translational Medicine

122

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We previously demonstrated that transplanting mesenchymal stem cells (MSCs) improved recovery from brain injury induced by severe intraventricular hemorrhage (IVH) in newborn rats. To assess the safety and feasibility of MSCs in preterm infants with severe IVH, we performed a phase I dose‐escalation clinical trial. The first three patients received a low dose of MSCs (5 × 106 cells/kg), and the next six received a high dose (1 × 107 cells/kg). We assessed adverse outcomes, including mortality and the progress of posthemorrhagic hydrocephalus. Intraventricular transplantation of MSCs was performed in nine premature infants with mean gestational age of 26.1 ± 0.7 weeks and birth weight of 808 ± 85 g at 11.6 ± 0.9 postnatal days. Treatment with MSCs was well tolerated, and no patients showed serious adverse effects or dose‐limiting toxicities attributable to MSC transplantation. There was no mortality in IVH patients receiving MSCs. Infants who underwent shunt surgery showed a higher level of interleukin (IL)‐6 in cerebrospinal fluid (CSF) obtained before MSC transplantation in comparison with infants who did not receive a shunt. Levels of IL‐6 and tumor necrosis factor‐α in initially obtained CSF correlated significantly with baseline ventricular index. Intraventricular transplantation of allogeneic human UCB‐derived MSCs into preterm infants with severe IVH is safe and feasible, and warrants a larger, and controlled, phase II study. Stem Cells Translational Medicine 2018;7:847–856

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Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial

Ahn

Chang

Sung

et al. 2018

Stem Cells Translational Medicine

122

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“…Up to now, several studies have demonstrated the feasibility and safety of autologous CB transfusion in premature neonates due to anemia, as well as in those requiring surgical intervention at the time of delivery. 23 Findings from experimental research investigations in developing animals have suggested that SPCs have the potential to treat the systemic insults typically encountered by preterm neonates, 15 and a variety of exogenous SC sources have been studied in experimental models of prematurity-related complications. 24 For example, the delivery of bone marrow-derived SCs mitigated inflammation, prevented vascular and neuronal damage, and improved exercise tolerance and survival in experimental oxygen-induced bronchopulmonary dysplasia in newborn rodents.…”

Section: Discussionmentioning

confidence: 99%

“…13 Together, the differences in the quantities of CB-circulating SPCs could contribute to fetal organ growth and to the pathogenesis of selected prematurity-related complications. The therapeutic potential of human CB cell transplant has been demonstrated in many animal models, including models investigating disorders of the nervous system, 14 respiratory system, 15 and the visual system. 16 Because premature neonates are rapidly deprived and deprived too early of a large amount of CB-circulating SPCs, preterm infants experience anemia, necessitating red blood cell (RBC) transfusion, mostly within a few days after birth.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2015

Exp Clin Transplant

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Objectives: This is a preliminary, single-center, prospective study in the field of autologous cord blood transplant. We investigated the feasibility, safety, and tolerability of autologous whole cord blood transplant in extremely premature infants as a potential therapeutic modality to prevent developing complications related to prematurity. Materials and Methods: This preliminary prospective study (ClinicalTrials.gov identifier NCT02050971) included preterm infants born at less than 32 weeks of gestational age who developed anemia because of prematurity. Infants were assigned to 2 groups: (1) those receiving an autologous cord blood transfusion within 5 days postpartum (n = 5) and (2) those who obtained only an allogeneic red blood cell transfusion when necessary (n = 9; control group). Vital measurements were performed during and after transfusion, and peripheral blood pH, hematocrit, glucose, and calcium and potassium ion levels were measured over the next 4 days. Results: Oxygen saturation was significantly increased throughout the cord blood transfusion and in the subsequent 48 hours. No significant differences were found in vital measurements, such as arterial blood pressure (mean, systolic, and diastolic) or heart rate over the first 48 hours posttransfusion. Similarly, no significant differences were found in biochemical analyses of blood with the exception of pH level. We found initial pH level to be significantly augmented in the cord blood recipient group by the first day after transplant, which remained significantly higher for next 24 hours compared with that shown in the control group. Conclusions: Collection, preparation, and short-term storage of unfrozen cord blood are feasible for clinical use. Our results showed general safety and tolerability of the procedure of whole autologous cord blood transplant in recruited preterm newborns. However, because our study group was small, these results need to be confirmed in further investigations with a larger patient cohort.

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“…Cell engraftment was low suggesting the PCs and MSCs may act via a paracrine effect. Assessment at six months showed no adverse lung effects [124] In a rat model, hyperoxia exposure led to air space enlargement, loss of lung capillaries and low expression of VEGF and eNOS. Transplanted endothelial progenitor cells, when combined with iNO, resulted in improved alveolarisation, microvessel density and upregulation of VEGF and eNOS proteins [125].…”

Section: Stem Cellsmentioning

confidence: 99%

Advances in emerging treatment options to prevent bronchopulmonary dysplasia

Ling

Greenough

2017

Expert Opinion on Orphan Drugs

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Introduction: Bronchopulmonary dysplasia (BPD) is common sequaelae of premature birth.It can be complicated by the development of pulmonary hypertension (PH), which significantly increases mortality. Areas covered: The aim of this review is to evaluate emerging drug therapies for prevention and treatment of BPD and associated PH. These include superoxide dismutase, macrolides, Clara secretary cell protein, -1 protease inhibitors, pentoxifylline, melatonin, inositol, N-acetyl cysteine, allopurinol, cimetidine, pulmonary vasodilators and mesenchymal stem cells (MSC). We have also included discussion on longer standing therapies such as corticosteroids, caffeine and vitamin A.Expert opinion: Corticosteroid administration systemically, but not by inhalation, caffeine and vitamin A reduce BPD. Enhancing endogenous anti-oxidant mechanisms through supplementation with superoxide dismutase or Clara cell secretory protein has yielded encouraging results. Azithromycin, a macrolide used to treat Ureaplasma infection, also has anti-inflammatory properties and has been shown to reduce BPD. Sildenafil reduces the echocardiographic markers of pulmonary hypertension associated with BPD, but has not been shown to prevent BPD. In animal models and a small phase one study MSC administration has resulted in promising results. Appropriately powered studies with long term outcomes are required to assess the efficacy of all these treatments.3

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Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia

Cited by 222 publications

References 35 publications

Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial

Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial

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Advances in emerging treatment options to prevent bronchopulmonary dysplasia

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