Treatment of experimental necrotizing enterocolitis with stem cell-derived exosomes

McCulloh, Christopher J.; Olson, Jacob K.; Wang, Yijie; Zhou, Yu; Tengberg, Natalie; Deshpande, Shivani; Besner, Gail E.

doi:10.1016/j.jpedsurg.2018.02.086

Cited by 74 publications

(79 citation statements)

References 28 publications

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“…Although it has been shown that several different types of SC reduce the incidence and severity of experimental NEC, SC research in clinical medicine is difficult and faces many ethical, legal, and scientific challenges, including a theoretical concern for potential tumorigenicity [2]. This concern led to a follow-up study, which examined EVs released from SC and their ability to protect the intestines from NEC.…”

Section: Discussionmentioning

confidence: 99%

“…Necrotizing enterocolitis (NEC) is a devastating disease of newborns, with mortality rates that remain as high as 20%-30%. The cost of treating infants with NEC exceeds $1 billion in the US each year [2]. Babies who survive NEC frequently have long term complications including short bowel syndrome, developmental delays and neurological sequelae [1][2][3].…”

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confidence: 99%

“…The cost of treating infants with NEC exceeds $1 billion in the US each year [2]. Babies who survive NEC frequently have long term complications including short bowel syndrome, developmental delays and neurological sequelae [1][2][3]. Unfortunately, despite much research over the past decades, a cure has not been identified.…”

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confidence: 99%

“…Previous research has demonstrated that different types of stem cells (SC) have the ability to reduce the incidence and severity of experimental NEC. Furthermore, extracellular vesicles (EVs) derived from SC are similarly protective against NEC, suggesting that they mediate the therapeutic effects of the SC from which they originate [1,2]. EVs are nanovesicles,~20-200 nm in size, that are released by many cells in the body and are ubiquitously present in body fluids including saliva, urine, and breast milk [4].…”

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confidence: 99%

“…EVs are nanovesicles,~20-200 nm in size, that are released by many cells in the body and are ubiquitously present in body fluids including saliva, urine, and breast milk [4]. Whereas prior studies relied on intraperitoneal (IP) administration of EVs for NEC therapy, [2], enteral administration would be more clinically relevant. Recent research has suggested that the enteral route could be a promising way to deliver EVs [5,6].…”

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confidence: 99%

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Human Breast Milk-Derived Extracellular Vesicles in the Protection Against Experimental Necrotizing Enterocolitis

Pisano

Galley

Elbahrawy

et al. 2020

Journal of Pediatric Surgery

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Purpose: Necrotizing enterocolitis (NEC) is a leading cause of death in premature infants. Breast feeding decreases the incidence of NEC but, even with aggressive promotion of nursing in Neonatal Intensive Care Units, morbidity and mortality remain high. Previous studies from our laboratory have demonstrated that extracellular vesicles (EVs) purified from mouse and rat stem cells can protect the intestines from NEC. The aim of this study was to determine whether human breast milk (BM)-derived EVs could prevent NEC. Methods: EVs were purified from human donor breast milk. NEC was induced in premature rat pups by exposure to asphyxia/hypothermia/hypercaloric feeds. Pups were randomized to: (1) breast fed, no injury, (2) NEC, (3) NEC + BM-derived EVs once intraperitoneally (IP), (4) NEC + BM-derived EVs enterally (PO) with each feed. Intestinal tracts were examined for histologic damage. Additionally, the effect of BM-derived EVs on intestinal epithelial cells (IEC) subjected to hypoxia/reoxygenation injury in vitro was examined. Results: NEC incidence was 0% in breast-fed pups and 62% in pups subjected to NEC. IP administration of BMderived EVs decreased NEC incidence to 29% and enteral administration further decreased NEC incidence to 11.9%. (p b 0.05). BM-derived EVs significantly increased cell proliferation and decreased apoptosis in IEC in vitro. Conclusion: Breast milk-derived EVs delivered either IP or enterally significantly decrease the incidence and severity of experimental NEC, protect IEC from injury in vitro, and may represent an innovative therapeutic option for NEC in the future. Type of study: Basic science study. Level of evidence: N/A.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

mentioning

confidence: 99%

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Human Breast Milk-Derived Extracellular Vesicles in the Protection Against Experimental Necrotizing Enterocolitis

Pisano

Galley

Elbahrawy

et al. 2020

Journal of Pediatric Surgery

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Neural stem/progenitor cell‐derived extracellular vesicles: A novel therapy for neurological diseases and beyond

Zhu

Wang

et al. 2023

MedComm

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As bilayer lipid membrane vesicles secreted by neural stem/progenitor cells (NSCs), NSC-derived extracellular vesicles (NSC-EVs) have attracted growing attention for their promising potential to serve as novel therapeutic agents in treatment of neurological diseases due to their unique physicochemical characteristics and biological functions. NSC-EVs exhibit advantages such as stable physical and chemical properties, low immunogenicity, and high penetration capacity to cross blood-brain barrier to avoid predicaments of the clinical applications of NSCs that include autoimmune responses, ethical/religious concerns, and the problematic logistics of acquiring fetal tissues. More importantly, NSC-EVs inherit excellent neuroprotective and neuroregenerative potential and immunomodulatory capabilities from parent cells, and display outstanding therapeutic effects on mitigating behavioral alterations and pathological phenotypes of patients or animals with neurological diseases. In this review, we first comprehensively summarize the progress in functional research and application of NSC-EVs in different neurological diseases, including neurodegenerative diseases, acute neurological diseases, dementia/cognitive dysfunction, and peripheral diseases. Next, we provide our thoughts on current limitations/concerns as well as tremendous potential of NSC-EVs in clinical applications. Last, we discuss future directions of further investigations on NSC-EVs and their probable applications in both basic and clinical research.

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Amniotic fluid and breast milk: a rationale for breast milk stem cell therapy in neonatal diseases

Filler

Chusilp

et al. 2020

Pediatr Surg Int

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Treatment of experimental necrotizing enterocolitis with stem cell-derived exosomes

Abstract: Basic science.

Cited by 74 publications

References 28 publications

Human Breast Milk-Derived Extracellular Vesicles in the Protection Against Experimental Necrotizing Enterocolitis

Human Breast Milk-Derived Extracellular Vesicles in the Protection Against Experimental Necrotizing Enterocolitis

Neural stem/progenitor cell‐derived extracellular vesicles: A novel therapy for neurological diseases and beyond

Amniotic fluid and breast milk: a rationale for breast milk stem cell therapy in neonatal diseases

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