AN69 Hollow Fiber Membrane will Reduce but Not Abolish the Risk of Transmission of Porcine Endogenous Retroviruses

As the risk of porcine endogenous retrovirus (PERV) infection is a major obstacle to the xenotransplantation of porcine tissue, we investigated whether an AN69 hollow fibre membrane, used for islets of Langerhans transplantation, could prevent the transfer of PERVs and thus reduce the risk of PERV infection. PK15 cells were used as a PERV source. A specific and highly sensitive RCR was used for detection of a PERV provirus DNA (gag region) and a porcine mtDNA. Human U293 cells were incubated in vitro with encapsulated PK15 cells, concentrated encapsulated PK15 supernatant, or concentrated PK15 supernatant as a control. CD1 mice were implanted in vivo with encapsulated PK15 cells or injected with PK15 supernatant. We found no infection in human cells incubated with either encapsulated PK15 supernatant or in 10 out of 11 samples after coincubation with encapsulated PK15 cells. Infection of human cells was, however, detected in 1 out of 11 samples after coincubation with encapsulated PK15 cells. The presence of PERV provirus DNA and porcine mtDNA was detected in all the investigated tissues of the mice injected with PK15 supernatant and in various tissues of the mice implanted with encapsulated PK15 cells. Four weeks after the last injection of PK15 supernatant or a fiber explantation, no mouse showed any presence of PERV provirus DNA or porcine mtDNA. Our results demonstrate that AN69 hollow fiber membrane will reduce but not abolish the risk of PERV infection. Because the real risk of PERV infection still remains unknown, it is necessary to investigate further the real protection that could be provided by hollow fibers to ensure the safety of clinical xenotransplantation.

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Pumping O2 with no N2: An Overview of Hollow Fiber Membrane Oxygenators with Integrated Arterial Filters

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666191210161013 ◽

2020 ◽

Vol 20 (1) ◽

pp. 78-85 ◽

Cited By ~ 1

Author(s):

Anxin Liu ◽

Zhiquan Sun ◽

Qier Liu ◽

Ning Zhu ◽

Shigang Wang

Keyword(s):

Hollow Fiber ◽

Hollow Fiber Membrane ◽

Experimental Studies ◽

Circulation System ◽

Fiber Membrane ◽

Priming Volume ◽

Membrane Oxygenators ◽

Set Up

The advancement of cardiac surgery benefits from the continual technological progress of cardiopulmonary bypass (CPB). Every improvement in the CPB technology requires further clinical and laboratory tests to prove its safety and effectiveness before it can be widely used in clinical practice. In order to reduce the priming volume and eliminate a separate arterial filter in the CPB circuit, several manufacturers developed novel hollow-fiber membrane oxygenators with integrated arterial filters (IAF). Clinical and experimental studies demonstrated that an oxygenator with IAF could reduce total priming volume, blood donor exposure and gaseous microemboli delivery to the patient. It can be easily set up and managed, simplifying the CPB circuit without sacrificing safety. An oxygenator with IAF is expected to be more beneficial to the patients with low body weight and when using a minimized extracorporeal circulation system. The aim of this review manuscript was to discuss briefly the concept of integration, the current oxygenators with IAF, and the in-vitro / in-vivo performance of the oxygenators with IAF.

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Hollow-fiber membrane technology: Characterization and proposed use as a potential mimic of skin vascularization towards the development of a novel skin absorption in vitro model

Biochemical Engineering Journal ◽

10.1016/j.bej.2019.01.025 ◽

2019 ◽

Vol 145 ◽

pp. 90-97

Author(s):

Patricia Perez Esteban ◽

Juliette Pickles ◽

Andrew D. Scott ◽

Marianne J. Ellis

Keyword(s):

Hollow Fiber ◽

In Vitro Model ◽

Hollow Fiber Membrane ◽

Membrane Technology ◽

Skin Absorption ◽

Fiber Membrane ◽

Vitro Model

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Human endothelial cells hollow fiber membrane bioreactor as a model of the blood vessel for in vitro studies

Journal of Artificial Organs ◽

10.1007/s10047-016-0902-0 ◽

2016 ◽

Vol 19 (3) ◽

pp. 270-277

Author(s):

Anna Ciechanowska ◽

Piotr Ladyzynski ◽

Grazyna Hoser ◽

Stanislawa Sabalinska ◽

Jerzy Kawiak ◽

...

Keyword(s):

Endothelial Cells ◽

Blood Vessel ◽

Hollow Fiber ◽

Membrane Bioreactor ◽

Hollow Fiber Membrane ◽

In Vitro Studies ◽

Fiber Membrane ◽

Human Endothelial Cells ◽

Hollow Fiber Membrane Bioreactor

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Comparison of Replication-Competent Molecular Clones of Porcine Endogenous Retrovirus Class A and Class B Derived from Pig and Human Cells

Journal of Virology ◽

10.1128/jvi.75.12.5465-5472.2001 ◽

2001 ◽

Vol 75 (12) ◽

pp. 5465-5472 ◽

Cited By ~ 53

Author(s):

Ulrich Krach ◽

Nicole Fischer ◽

Frank Czauderna ◽

Ralf R. Tönjes

Keyword(s):

Genomic Library ◽

Endogenous Retrovirus ◽

Human Cells ◽

Endogenous Retroviruses ◽

Class A ◽

Infectious Risk ◽

Porcine Endogenous Retrovirus ◽

293 Cells ◽

Class B

ABSTRACT Vertically transmitted endogenous retroviruses pose an infectious risk in the course of pig-to-human transplantation of cells, tissues, and organs. Two classes of polytropic type C porcine endogenous retroviruses (PERV) which are infectious for human cells in vitro are known. Recently, we described the cloning and characterization of replication-competent PERV-B sequences from productively infected human cells (F. Czauderna, N. Fischer, K. Boller, R. Kurth, and R. R. Tönjes, J. Virol. 74:4028–4038, 2000). Here, we report the isolation of infectious molecular PERV-A and PERV-B clones from pig cells and compare these proviruses with clones derived from infected human 293 cells. In addition to clone PERV-A(42) derived from 293 cells, four “native” full-length proviral PERV sequences derived from a genomic library of the porcine cell line PK15 were isolated. Three identical class A clones, designated PK15-PERV-A(42), PK15-PERV-A(45), and PK15-PERV-A(58), and one class B clone, PK15-PERV-B(213), were characterized. PK15-PERV-B(213) is highly homologous but distinct from the previously described clone PERV-B(43). PK15-PERV-A(58) demonstrates close homology to PERV-A(42) inenv and to PERV-C in long terminal repeat,gag, and pro/polsequences. All three PERV clones described here were replication competent upon infection of susceptible cell lines. The findings suggest that the pig genome harbors a limited number of infectious PERV-A and -B sequences.

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Detection and Characterization of Porcine Endogenous Retrovirus in Porcine Plasma and Porcine Factor VIII

Journal of Virology ◽

10.1128/jvi.75.10.4551-4557.2001 ◽

2001 ◽

Vol 75 (10) ◽

pp. 4551-4557 ◽

Cited By ~ 33

Author(s):

Daniel M. Takefman ◽

Susan Wong ◽

Thomas Maudru ◽

Keith Peden ◽

Carolyn A. Wilson

Keyword(s):

Factor Viii ◽

Mononuclear Cells ◽

Infectious Virus ◽

Endogenous Retrovirus ◽

Endogenous Retroviruses ◽

Peripheral Blood Mononuclear ◽

Porcine Endogenous Retrovirus ◽

Pig Genome

ABSTRACT The pig genome contains porcine endogenous retroviruses (PERVs) capable of infecting human cells. Detection of infectious retrovirus in porcine peripheral blood mononuclear cells and endothelial cells suggested to us that pig plasma is likely to contain PERV. Both PERV env sequences and viral reverse transcriptase (RT) activity were detected in all plasma samples isolated from four NIH minipigs. To detect infectious virus from plasma, we performed a culture assay using three cell lines of feline, swine, and human origin that had previously been shown to be permissive for PERV. Infectious virus was successfully cultured from all four NIH minipig plasmas on the swine cell line ST-IOWA. Using RT-PCR with env-specific primers, we could detect expression of PERV class C envelope in the supernatant of ST-IOWA cells that had been exposed to each pig plasma. We next examined a pig plasma derivative, Hyate:C (porcine factor VIII), and found evidence of PERV particles, since all six lots examined were positive for PERV RNA and RT activity. However, infectious virus could not be detected in clinical lots of Hyate:C, suggesting that the manufacturing process might reduce the load of infectious virus to levels below detectable limits of the assay. Detection of infectious virus in porcine plasma confirms and extends the previous findings that certain porcine cells express PERV when manipulated in vitro and clearly demonstrates that there are porcine cells that express infectious PERV constitutively in vivo.

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Survival Analysis of Escherichia coli Encapsulated in a Hollow Fiber Membrane In Vitro and In Vivo: Preliminary Report

Cell Transplantation ◽

10.3727/000000005783983043 ◽

2005 ◽

Vol 14 (5) ◽

pp. 323-330 ◽

Cited By ~ 5

Author(s):

L. H. Granicka ◽

M. Wdowiak ◽

A. Kosek ◽

S. Świezewski ◽

D. Wasilewska ◽

...

Keyword(s):

Hollow Fiber ◽

Fluorescent Protein ◽

Culture Media ◽

Hollow Fiber Membrane ◽

In Vitro Experiments ◽

Bacteria Growth ◽

E Coli ◽

Green Fluorescent

The purpose of the observations was the viability and quality evaluation of E. coli bacteria encapsulated in hollow fiber membranes (HF) in short in vivo and in vitro experiments. A polypropylene, surface-modified hollow fiber was applied for immunoisolation of E. coli bacteria transfected with a green fluorescent protein (E. coli GFPI). The presence of GFP fluorescence of organisms was assessed with the use of flow cytometry. The E. coli GFPIs were then observed for the period of 5 days in in vitro experiments in the culture medium. A single IPTG (isopropyl β-D-1-thiogalactopyranoside) induction of GFP gene appeared to be adequate for an expression of GFP protein for 5 days. The GFP expression values observed for E. coli GFPs encapsulated in HF during culture in different culture media were comparable. The survival of E. coli GFPIs encapsulated in HF after 1, 2, 4, or 5 days of subcutaneous implantation into mice was evaluated. The explanted E. coli GFPIs exhibited mean expression 603 ± 17 (n = 32) units of fluorescence during the implantation period. The values obtained were comparable for selected days of observation. It was observed that the membranes applied ensured the bacteria growth within the HF's space only.

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Oxygen transfer characteristics of a hollow fiber dialyser: toward possible repurposing of dialysers as blood oxygenators in the context of constrained availability of respiratory support

10.1101/2020.04.06.20055236 ◽

2020 ◽

Author(s):

David M. Rubin ◽

Neil T. Stacey ◽

Tonderayi Matambo ◽

Diane Hildebrandt

Keyword(s):

Hollow Fiber ◽

Oxygen Transfer ◽

Resource Constraints ◽

Hollow Fiber Membrane ◽

Oxygen Demand ◽

Respiratory Support ◽

Pure Oxygen ◽

Fiber Membrane ◽

Transfer Characteristics

The mass transfer characteristics for oxygen from the gas phase to blood in a hollow fiber membrane dialyser was investigated in vitro with a view to using such devices to effect respiratory support in patients with viral pneumonia and acute respiratory distress syndrome. In our in vitro experiments, which were severely curtailed by prevailing circumstances, we used water as a substitute on the blood side. The water was saturated rapidly indicating that the system was flow limited rather than diffusion limited for oxygen transfer. Using these findings, we estimated the expected performance with blood and the results suggest that two hollow fiber membrane dialysers operating in parallel with a pure oxygen gas supply running counter-current to the blood flow, could supply up to 40% of the total required oxygen demand rate in an adult patient. While not studied, carbon dioxide elimination is likely to be feasible as well. It is thus possible that hollow fiber dialysis units operating with suitable roller pumps in a veno-venous access configuration, could serve as a cost-effective and readily available alternative or adjunct for respiratory support in the face of severe resource constraints. Verification and extension of our study is needed by well resourced laboratories who are still able to function during this unprecedented period of restrictions. If, after further studies and clinical considerations, this approach appears feasible, then consideration may be given to clinical deployment of this technique in desperate situations where no alternative exists to preserve life.

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