Selective inhibition of cyclooxygenase‐2 protects porcine aortic endothelial cells from human antibody‐mediated complement‐dependent cytotoxicity

Chen, Pengfei; Zhao, Yanli; Gao, Hanchao; Huang, Jiabao; Lu, Ying; Song, Jingyu; Lin, Lizhong; Lin, Zejin; Ou, Chunpei; Sun, Huimin; Zeng, Changchun; Cooper, David K. C.; Yu, Zhan; Deng, Xiaofang; Mou, Lisha

doi:10.1111/xen.12536

Cited by 4 publications

(3 citation statements)

References 65 publications

(132 reference statements)

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“…Given the challenges associated with ongoing attempts to engineer transplantable pig organs by means of genetic engineering 62 or whole organ perfusion decellularization/recellularization 63 , we believe that our approach (illustrated in Fig. 6 ) may provide a significant shortcut in the efforts to generate an unlimited supply of transplantable, immunologically-acceptable organs for future translation into clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Generation of vascular chimerism within donor organs

Cohen

Partouche

Gurevich

et al. 2021

Sci Rep

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Whole organ perfusion decellularization has been proposed as a promising method to generate non-immunogenic organs from allogeneic and xenogeneic donors. However, the ability to recellularize organ scaffolds with multiple patient-specific cells in a spatially controlled manner remains challenging. Here, we propose that replacing donor endothelial cells alone, while keeping the rest of the organ viable and functional, is more technically feasible, and may offer a significant shortcut in the efforts to engineer transplantable organs. Vascular decellularization was achieved ex vivo, under controlled machine perfusion conditions, in various rat and porcine organs, including the kidneys, liver, lungs, heart, aorta, hind limbs, and pancreas. In addition, vascular decellularization of selected organs was performed in situ, within the donor body, achieving better control over the perfusion process. Human placenta-derived endothelial progenitor cells (EPCs) were used as immunologically-acceptable human cells to repopulate the luminal surface of de-endothelialized aorta (in vitro), kidneys, lungs and hind limbs (ex vivo). This study provides evidence that artificially generating vascular chimerism is feasible and could potentially pave the way for crossing the immunological barrier to xenotransplantation, as well as reducing the immunological burden of allogeneic grafts.

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Section: Discussionmentioning

confidence: 99%

Generation of vascular chimerism within donor organs

Cohen

Partouche

Gurevich

et al. 2021

Sci Rep

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“…Another important member of the cytokine family associated with COVID-19 is interleukin-1β, a key regulator of inflammatory response, with the ability to stimulate the release of other cytokines such as IL-17, IL-21, and IL-22. Interleukin-1β and tumor necrosis factor alpha both contribute to pain associated with inflammation via the induction of cyclooxygenase-2 in the nervous system [27]. This may play a role in the severe headache associated with COVID-19 infection.…”

Section: Pro-inflammatory Cytokinesmentioning

confidence: 99%

Mechanisms of COVID-19-induced heart failure: a short review

2020

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected more than 42.5 million people globally resulting in the death of over 1.15 million subjects. It has inflicted severe public health and economic hardships across the world. In addition to acute respiratory distress syndrome, respiratory failure, sepsis, and acute kidney injury, COVID-19 also causes heart failure (HF). COVID-19-induced HF is manifested via different mechanisms, including, but not limited to, (1) virus-induced infiltration of inflammatory cells, which could impair the function of the heart; (2) pro-inflammatory cytokines (monocyte chemoattractant protein-1, interleukin-1β; interleukin-6; tumor necrosis factor-α) that could cause necrosis and death of the myocardium; (3) endothelial injury coupled with micro-thrombosis which could damage the endocardium; and (4) acute respiratory distress syndrome and respiratory failure that could lead to heart failure due to severe hypoxia. It is concluded that the etiology of COVID-19-induced HF is multifactorial and mitigation of the development of HF in patients with COVID-19 will require different approaches such as social distancing, drug therapy, and the urgent development of a vaccine to eradicate the disease.

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“…However, the exact mechanism that regulates COX‐2 expression and the function of COX‐2 on PAECs remain unknown. Chen et al aimed to investigate this using an in vitro pig‐to‐primate xenotransplantation model and an in vivo pig‐to‐mouse cellular transplant model . Human serum‐induced COX‐2 expression in PAECs increased in a time‐ and dose‐dependent manner.…”

Section: Improving Xenograft Outcomes Through Genetic Modificationsmentioning

confidence: 99%

Xenotransplantation literature update, November/December 2019

Thomas

Hawthorne

Burlak

2020

Xenotransplantation

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The ever-increasing disparity between the lack of organ donors and patients on the transplant waiting list is increasing worldwide. For the past several decades xenotransplantation has led the way to correct this deficit and remains clearly the only feasible option to provide a means to meet the demand for patients in need of an organ transplant. Xenotransplantation's ability to provide a specifically designed unlimited supply of organs, suited to treat the various needs for transplant organs and cells, has recently been championed by successful pre-clinical trials that have run long-term in non-human primate studies.In this review we show how these improvements have come about due to longterm dedicated research and recent advances in biomedical engineering technology, such as genome editing tools including zinc finger nucleases, TALEN, and CRISPER/ Cas9 which have paved the way for significant breakthroughs in improving xenograft outcomes through genetic modifications to the donor source pig. Other novel approaches include the development of decellularized porcine tissue, such as corneas which can now be transplanted into patients with the minimal need for immunosuppression or other side effects. Further genetic variants of the porcine genome are also now being optimized to abrogate rejection. The emergence of new modalities such as; mesenchymal stem cells, donor thymic vascularization, in vivo bioreactors, chemokine and cytokine therapies have come to show improvements in xenograft outcomes. Furthermore, new studies confirm the safety status of using porcine xenografts, verifying that with current technologies and approaches, the issue of PERV transmission is a moot point. These breakthroughs and technological advancements push the reality of xenotransplantation one step closer to the clinic. K E Y W O R D S complement regulation, CRISPR, Mesenchymal stem cells, zoonosis

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Selective inhibition of cyclooxygenase‐2 protects porcine aortic endothelial cells from human antibody‐mediated complement‐dependent cytotoxicity

Cited by 4 publications

References 65 publications

Generation of vascular chimerism within donor organs

Generation of vascular chimerism within donor organs

Mechanisms of COVID-19-induced heart failure: a short review

Xenotransplantation literature update, November/December 2019

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