Ethics and Policy Issues for Stem Cell Research and Pulmonary Medicine

Lowenthal, Justin; Sugarman, Jeremy

doi:10.1378/chest.14-1696

Cited by 14 publications

(24 citation statements)

References 78 publications

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“…It is crucial that ethical and regulatory considerations be interpreted in the broader context of both consensus and controversies about stem cell research and stem cell donation for and by children. Debate continues about the moral status about human embryo-derived stem cells, the use of stem cells in research, and the influence of commercial entities that stand to benefit from proprietary discoveries (6,7). Additional consideration must be given to ethical complexities when children are potential stem cell donors (8) and to routine umbilical cord blood cell banking, which is costly for families and likely never to be used for treatment (9).…”

Section: Regulatory and Ethical Complexitiesmentioning

confidence: 99%

Hope vs. caution: ethical and regulatory considerations for neonatal stem cell therapies

2018

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T he Annual Review issue of Pediatric Research contains important reviews and original reports focusing on stem cell therapy for the treatment of neonatal lung disease (1), pediatric brain injury (2), congenital anomalies (3), and congenital heart disease (4). The authors describe the potential of these approaches to advance the care of children with life-threatening conditions and those with significant long-term chronic morbidities. The authors also describe the promise, ethical challenges, and limitations of these evolving therapeutic approaches. In considering these important advances, several themes are worthy of consideration, especially as related to potential cell-based therapies in neonates. These themes can be broadly categorized into study design, recruitment, funding and sponsorship, and ethical and regulatory complexities.

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Section: Regulatory and Ethical Complexitiesmentioning

confidence: 99%

Hope vs. caution: ethical and regulatory considerations for neonatal stem cell therapies

2018

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“…Previous cell-based treatments have focused on bone marrow-derived stem cells (BMSCs), which have demonstrated therapeutic functions in human and rodent tissue models of ALI/ARDS 13 – 16 . However, there are several obstacles to the clinical application of BMSCs, including the fact that their isolation is an invasive, painful, and relatively expensive process and more importantly, the numbers of cells that can be obtained from bone marrow is low 17 , 18 . ADSCs have also received attention because of their positive outcomes in terms of tissue regeneration and repair.…”

Section: Introductionmentioning

confidence: 99%

Autologous transplantation of adipose-derived stromal cells combined with sevoflurane ameliorates acute lung injury induced by cecal ligation and puncture in rats

Liang

Zhou

Tang

et al. 2020

Sci Rep

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Adipose-derived stromal cells (ADScs) have excellent capacities for regeneration and tissue protection, while sevoflurane, as a requisite component of surgical procedures, has shown therapeutic benefit in animal models of sepsis. This study therefore determined if the combination of sevoflurane and ADSCs exerted additional protective effects against acute lung injury (ALI) induced by cecal ligation and puncture (CLP) in rats. The animals were randomized into five groups: (sham operation (group I), CLP followed by mechanical ventilation (group II), CLP plus sevoflurane at 0.5 minimum alveolar concentration (group III), CLP plus intravenous autologous 5 × 10 6 ADScs (group iV), and CLP plus sevoflurane and ADSCs (group V). Levels of the pro-inflammatory cytokines tumor necrosis factor-α, transforming growth factor-β1, interleukin-1β and interleukin-6 were significantly increased in CLP rats. Moreover, epithelial sodium channel expression levels and activities of Na/K-ATPase and alveolar fluid clearance were significantly reduced in CLP-induced ALI rats. ADSCs improved all these parameters, and these effects were further enhanced by the addition of sevoflurane. In conclusion, combined treatment with ADSCs and sevoflurane is superior to either ADSCs or sevoflurane therapy alone for preventing ALI. This beneficial effect may be partly due to improved alveolar fluid clearance by the paracrine or systemic production of keratinocyte growth factor and via anti-inflammatory properties. Acute respiratory distress syndrome (ARDS) and its early stage, acute lung injury (ALI), represent a devastating clinical syndrome characterized by lung tissue edema and acute hypoxemic respiratory failure, finally leading to lung fibrogenesis. Despite extensive research efforts, mortality among critically ill patients remains high (about 40%) 1. Alveolar fluid clearance (AFC) is generally believed to be the main mechanism responsible for clearing edema fluid from airspaces into the lung interstitium 1. Sodium ions enter alveolar type II epithelial cells primarily through the epithelial sodium channel (ENaC) expressed at the apical surface, composed of α, β, and γ subunits, and are pumped out by Na/K-ATPase on the basolateral surface, driving osmotic water transport 2-4. However, AFC can be reduced by multiple pathways that impair ENaC and/or Na/K-ATPase, such as high tidal volume ventilation, hypoxia, and pro-inflammatory cytokines 5-7. Previous studies found that patients with ALI/ARDS were also characterized by reduced AFC. Clearance of excessive pulmonary edema is thus key to ensuring effective treatment and improving survival 8,9. Increasing numbers of in vivo experimental and preliminary clinical studies have identified mesenchymal stem cells (MSCs) as a promising therapy for various pulmonary diseases, including ALI 10-12. MSCs have the capacity to restore injured tissues by producing several growth factors, as well as immunomodulatory and open

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“…In previous cell‐based treatments, majority of attention has been focused on bone marrow‐derived stem cells (BMSCs), which have therapeutic function in human and rodent tissue models of ALI/ARDS (Bustos et al, 2013; Caplan, 2007; Hao et al, 2015; Jones & Rankin, 2011; Pittenger et al, 1999). However, a lot of obstructions that can restrict the clinical reasonable application of BMSCs have been identified, such as isolation of BMSCs is invasive, painful, and relatively expensive process and more important, and the numbers of cells that can be obtained from bone marrow are very few (Lowenthal & Sugarman, 2015; Pittenger & Martin, 2004). Adipose‐derived stromal cells (ADSCs) have been given great attention attributing to its positive outcome on tissue regeneration and repair.…”

Section: Introdctionmentioning

confidence: 99%

Enhanced protection against lipopolysaccharide‐induced acute lung injury by autologous transplantation of adipose‐derived stromal cells combined with low tidal volume ventilation in rats

Liang

Yin

Sun

et al. 2020

Journal Cellular Physiology

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Adipose-derived stromal cells (ADSCs) showed excellent capacity in regeneration and tissue protection. Low tidal volume ventilation (LVT) strategy demonstrates a therapeutic benefit on the treatment of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). This study, therefore, aimed to undertaken determine whether the combined LVT and ADSCs treatment exerts additional protection against lipopolysaccharide (LPS)-induced ALI in rats. The animals were randomized into seven groups: Group I (control), Group II (instillation of LPS at 10 mg/kg intratracheally), Group III (LPS+LVT 6 ml/kg), Group IV (LPS+intravenous autologous 5 × 10 6 ADSCs which were pretreated with a scrambled small interfering RNA [siRNA] of keratinocyte growth factor [KGF] negative control), Group V (LPS+ADSCs which were pretreated with a scrambled siRNA of KGF, Group VI (LPS+LVT and ADSCs as in the Group IV), and Group VII (LPS+LVT and ADSCs as in the Group V). We found that levels of tumor necrosis factor-α, transforming growth factor-β1, and interleukin (IL)-1β and IL-6, the proinflammatory cytokines, were remarkably increased in LPS rats. Moreover, the expressions of ENaC, activity of Na, K-ATPase, and alveolar fluid clearance (AFC) were obviously reduced by LPS-induced ALI. The rats treated by ADSCs showed improved effects in all these changes of ALI and further enhanced by ADSCs combined with LVT treatment. Importantly, the treatment of ADSCs with siRNA-mediated knockdown of KGF partially eliminated the therapeutic effects. In conclusion, combined treatment with ADSCs and LVT not only is superior to either ADSCs or LVT therapy alone in the prevention of ALI. Evidence of the beneficial effect may be partly due to improving AFC by paracrine or systemic production of KGF and anti-inflammatory properties.

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Ethics and Policy Issues for Stem Cell Research and Pulmonary Medicine

Cited by 14 publications

References 78 publications

Hope vs. caution: ethical and regulatory considerations for neonatal stem cell therapies

Hope vs. caution: ethical and regulatory considerations for neonatal stem cell therapies

Autologous transplantation of adipose-derived stromal cells combined with sevoflurane ameliorates acute lung injury induced by cecal ligation and puncture in rats

Enhanced protection against lipopolysaccharide‐induced acute lung injury by autologous transplantation of adipose‐derived stromal cells combined with low tidal volume ventilation in rats

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