Publications: Australian Animal Experimentation

@article{nokey,

title = {Chronic outcomes after mild-moderate traumatic brain injury in adult seizure-prone (FAST) and seizure-resistant (SLOW) rats: A model for understanding genetic contributions to acquired epileptogenesis?},

author = {Wai Lam Leung, Ali Shada, Piero Peruccaa, Terence J. O’Brien, Bridgette D. Semple, Pablo M. Casillas-Espinosa},

url = {https://www.epilepsybehavior.com/article/S1525-5050(25)00086-1/fulltext},

doi = {https://doi.org/10.1016/j.yebeh.2025.110347},

year  = {2025},

date = {2025-05-01},

urldate = {2025-05-01},

journal = {Epilepsy & Behavior},

volume = {166},

pages = {110347},

abstract = {This study looked at how genetics affect the risk of epilepsy after a brain injury. Researchers compared two types of rats: FAST rats, which are more prone to seizures, and SLOW rats, which are more resistant. After a mild brain injury, FAST rats had stronger early seizure-like responses, while SLOW rats showed more movement problems. Over time, both types of rats behaved differently, but the brain injury didn’t cause long-term epilepsy. Some abnormal brain activity was seen in FAST rats, but no full seizures. The study suggests that a different injury model may be needed to better understand the genetic risk for epilepsy.},

note = {Monash University},

keywords = {Epilepsy, Rats, TBI},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Developmental air pollution exposure augments airway hyperreactivity, alters transcriptome, and DNA methylation in female adult progeny},

author = {Razia Zakarya, Yik Lung Chan, Baoming Wang, Andrew Thorpe, Dikaia Xenaki, Kin Fai Ho, Hai Guo, Hui Chen, Brian G Oliver, Christopher O'Neill},

url = {https://pmc.ncbi.nlm.nih.gov/articles/PMC11890619/},

doi = {https://doi.org/10.1038/s42003-025-07835-0},

year  = {2025},

date = {2025-03-08},

urldate = {2025-03-08},

journal = {Communications Biology},

volume = {8},

number = {400},

abstract = {Exposure to air pollution during pregnancy can increase the risk and severity of asthma in children, but scientists don’t fully understand why. This study used a mouse model to explore how air pollution affects gene activity. Researchers found that offspring of mothers exposed to pollution had worse asthma symptoms and a weaker gene response to allergens. They also discovered changes in DNA markers (epigenetics) that may help explain how pollution exposure in the womb leads to lasting effects on lung health. These findings suggest that air pollution during pregnancy may make children more vulnerable to asthma by altering how their genes function.},

note = {School of Life Sciences, University of Technology Sydney, Sydney, Australia},

keywords = {Asthma, Mice},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Advancing the genetic engineering toolbox by combining AsCas12a knock-in mice with ultra-compact screening},

author = {Wei Jin, Yexuan Deng, John E. La Marca, Emily J. Lelliott, Sarah T. Diepstraten, Christina König, Lin Tai, Valentina Snetkova, Kristel M. Dorighi, Luke Hoberecht, Millicent G. Hedditch, Lauren Whelan, Geraldine Healey, Dan Fayle, Kieran Lau, Margaret A. Potts, Moore Z. Chen, Angus P. R. Johnston, Yang Liao, Wei Shi, Andrew J. Kueh, Benjamin Haley, Jean-Philippe Fortin & Marco J. Herold },

url = {https://www.nature.com/articles/s41467-025-56282-2},

doi = {https://doi.org/10.1038/s41467-025-56282-2},

year  = {2025},

date = {2025-01-30},

urldate = {2025-01-30},

journal = {Nature Communications},

volume = {16},

number = {974},

abstract = {Scientists developed a genetically modified mouse that continuously produces the gene-editing tool Cas12a, allowing them to edit genes in living animals, including for cancer research. They created gene-editing libraries to study gene function and analysed immune cells from the spleen, bone marrow and lymph nodes using flow cytometry. Some mice received bone marrow transplants after radiation to study blood cell regeneration, while others developed lymphoma and were euthanised for further study. Scientists also switched specific genes on or off in immune cells to investigate their role in disease and immunity.},

note = {Olivia Newton-John Cancer Research Institute, Heidelberg, Melbourne, Australia},

keywords = {Gene-editing, Mice},

pubstate = {published},

tppubtype = {article}

}

@article{,

title = {Rapid degeneration and neurochemical plasticity of the lateral geniculate nucleus following lesions of the primary visual cortex in marmoset monkeys},

author = {Gaoyuan Ma, Jonathan M Chan, Katrina H Worthy, Marcello GP Rosa, Nafiseh Atapour},

url = {https://pmc.ncbi.nlm.nih.gov/articles/PMC11697716/},

doi = {10.1016/j.crneur.2024.100141},

year  = {2024},

date = {2024-11-28},

urldate = {2024-11-28},

journal = {Current Research in Neurobiology},

volume = {28:8},

issue = {100141},

abstract = {Lesions of the primary visual cortex (V1) cause retrograde neuronal degeneration, volume loss and neurochemical changes in the lateral geniculate nucleus (LGN). Here we characterised the timeline of these processes in adult marmoset monkeys, after various recovery times following unilateral V1 lesions.},

note = {Monash University},

keywords = {Marmosets, Non-human primates},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {The role of frontopolar cortex in adjusting the balance between response  execution and action inhibition in anthropoids},

author = {Azadeh Feizpour, Mark J. Buckley, Inaki C. Mundinano, Marcello G.P. Rosa, Farshad Alizadeh Mansouri},

doi = {https://doi.org/10.1016/j.pneurobio.2024.102671},

year  = {2024},

date = {2024-10-05},

urldate = {2024-10-05},

journal = {Progress in Neurobiology},

volume = {241},

number = {102671},

abstract = {Executive control of behaviour entails keeping a fine balance between response execution and action inhibition. The most anterior part of the prefrontal cortex (frontopolar cortex) is highly developed in anthropoids; however, no previous study has examined its essential (indispensable) role in regulating the interplay between action execution and inhibition. In this cross-species study, we examine the performance of humans and macaque monkeys in the context of a stop-signal task and then assess the consequence of selective and bilateral damage to frontopolar cortex on monkeys’ behaviour. Humans and monkeys showed significant within-session practice related adjustments in both response execution (increase in response time (RT) and decrease in response variabilities) and action inhibition (enhanced inhibition). Furthermore, both species expressed context-dependent (post-error and post-stop) behavioral adjustments. In post-lesion testing, frontopolar-damaged monkeys had a 

longer RT and lower percentage of timeout trials, compared to their pre-lesion performance. The practice-related changes in mean RT and in RT variability were significantly heightened in frontopolar-damaged monkeys. They also showed attenuated post-error, but exaggerated post-stop, behavioural adjustments. Importantly, frontopolar damage had no significant effects on monkeys’ inhibition ability. Our findings indicate that frontopolar cortex plays a critical role in allocation of control to response execution, but not action inhibition.},

note = {Monash University},

keywords = {Macaque, Non-human primates},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Cholesterol as an inbuilt immunoadjuvant for a lipopeptide vaccine against group A Streptococcus infection},

author = {Nedaa Alharbi et al },

url = {https://doi.org/10.1016/j.jcis.2024.02.134},

doi = {10.1016/j.jcis.2024.02.134},

year  = {2024},

date = {2024-06-00},

journal = {Journal of Colloid and Interface Science Journal of Colloid and Interface Science},

volume = {663},

pages = {43052},

abstract = {Peptide-based vaccines can trigger highly specific immune responses, although peptides alone are usually unable to confer strong humoral or cellular immunity. Consequently, peptide antigens are administered with immunostimulatory adjuvants, but only a few are safe and effective for human use. To overcome this obstacle, herein a peptide antigen was lipidated to effectively anchor it to liposomes and emulsion. A peptide antigen B cell epitope from Group A Streptococcus M protein was conjugated to a universal T helper epitope, the pan DR-biding epitope (PADRE), alongside a lipidic moiety cholesterol. Compared to a free peptide antigen, the lipidated version (LP1) adopted a helical conformation and self-assembled into small nanoparticles. Surprisingly, LP1 alone induced the same or higher antibody titers than liposomes or emulsion-based formulations. In addition, antibodies produced by mice immunized with LP1 were more opsonic than those induced by administering the antigen with incomplete Freund’s adjuvant. No side effects were observed in the immunized mice and no excessive inflammatory immune responses were detected. Overall, this study demonstrated how simple conjugation of cholesterol to a peptide antigen can produce a safe and efficacious vaccine against Group A Streptococcus – the leading cause of superficial infections and the bacteria responsible for deadly post-infection autoimmune disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Oral nanotherapeutic formulation of insulin with reduced episodes of hypoglycaemia},

author = {Nicholas J. Hunt, Glen P. Lockwood, Scott J. Heffernan, Jarryd Daymond, Meng Ngu, Ramesh K. Narayanan, Lara J. Westwood, Biswaranjan Mohanty, Lars Esser, Charlotte C. Williams, Zdenka Kuncic, Peter A. G. McCourt, David G. Le Couteur, Victoria C. Cogger},

url = {https://www.nature.com/articles/s41565-023-01565-2},

doi = {10.1038/s41565-023-01565-2},

year  = {2024},

date = {2024-01-02},

urldate = {2024-01-02},

journal = {Nat. Nanotechnol.},

volume = {19},

pages = {534–544},

abstract = {Injectable insulin is an extensively used medication with potential life-threatening hypoglycaemic events. Here we report on insulin-conjugated silver sulfide quantum dots coated with a chitosan/glucose polymer to produce a responsive oral insulin nanoformulation. This formulation is pH responsive, is insoluble in acidic environments and shows increased absorption in human duodenum explants and Caenorhabditis elegans at neutral pH. The formulation is sensitive to glucosidase enzymes to trigger insulin release. It is found that the formulation distributes to the liver in mice and rats after oral administration and promotes a dose-dependent reduction in blood glucose without promoting hypoglycaemia or weight gain in diabetic rodents. Non-diabetic baboons also show a dose-dependent reduction in blood glucose. No biochemical or haematological toxicity or adverse events were observed in mice, rats and non-human primates. The formulation demonstrates the potential to orally control blood glucose without hypoglycaemic episodes.},

note = {The University of Sydney, Camperdown, New South Wales, Australia},

keywords = {Mice},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Superior efficacy of a skin-applied microprojection device for delivering a novel Zika DNA vaccine},

author = {Wijesundara, Danushka K. et al.},

url = {https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(23)00274-3},

doi = {https://doi.org/10.1016/j.omtn.2023.102056},

year  = {2023},

date = {2023-12-12},

urldate = {2023-12-12},

journal = {Molecular Therapy },

volume = {34},

abstract = {Zika virus (ZIKV) infections are spreading silently with limited global surveillance in at least 89 countries and territories. There is a pressing need to develop an effective vaccine suitable for equitable distribution globally. Consequently, we previously developed a proprietary DNA vaccine encoding secreted non-structural protein 1 of ZIKV (pVAX-tpaNS1) to elicit rapid protection in a T cell-dependent manner in mice. In the current study, we evaluated the stability, efficacy, and immunogenicity of delivering this DNA vaccine into the skin using a clinically effective and proprietary high-density microarray patch (HD-MAP). Dry-coating of pVAX-tpaNS1 on the HD-MAP device resulted in no loss of vaccine stability at 40°C storage over the course of 28 days. Vaccination of mice (BALB/c) with the HD-MAP-coated pVAX-tpaNS1 elicited a robust anti-NS1 IgG response in both the cervicovaginal mucosa and systemically and afforded protection against live ZIKV challenge. Furthermore, the vaccination elicited a significantly higher magnitude and broader NS1-specific T helper and cytotoxic T cell response in vivo compared with traditional needle and syringe intradermal vaccination. Overall, the study highlights distinctive immunological advantages coupled with an excellent thermostability profile of using the HD-MAP device to deliver a novel ZIKV DNA vaccine},

keywords = {Mice},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {H3K4me3 remodeling induced acquired resistance through O-GlcNAc transferase},

author = {Menon, D.R. et al},

url = {https://www.sciencedirect.com/science/article/pii/S1368764623000766?via%3Dihub

},

year  = {2023},

date = {2023-11-01},

urldate = {2023-11-01},

journal = {Drug Resistance Updates},

volume = {71},

note = {University of Queensland},

keywords = {Mice},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice},

author = {Vijayendra Dasari, et al },

doi = {https://doi.org/10.1038/s41467-023-39770-1},

year  = {2023},

date = {2023-08-08},

journal = {Nature Communications},

volume = {14},

number = {4371},

note = {QIMR Berghofer Medical Research Institute, Brisbane, Australia},

keywords = {Mice},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Modifying effects of sodium selenate in a model of drug resistant, temporal lobe epilepsy},

author = {Pablo Miguel Casillas-Espinosa, Alison Anderson, Anna Harutyunyan, Crystal Li, Jiyoon Lee, Emma L Braine, Rhys D Brady, Mujun Sun, Cheng Huang, Christopher K Barlow, Anup D Shah, Ralf B Schittenhelm, Richelle Mychasiuk, Nigel C Jones, Sandy R Shultz, Terence J O’Brien },

url = {https://elifesciences.org/articles/78877},

doi = { https://doi.org/10.7554/eLife.78877},

issn = {2050-084X},

year  = {2023},

date = {2023-03-09},

urldate = {2023-03-09},

journal = {eLife Sciences},

keywords = {Rats},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {A repeated measures cognitive affective bias test in rats: comparison with forced swim test},

author = {Benjamin Aliphon ,Twain Dai, Jessica Moretti, Marissa Penrose-Menz, Wilhelmina H A M Mulders, Dominique Blache, Jennifer Rodger},

url = {https://pubmed.ncbi.nlm.nih.gov/36450831/},

doi = {10.1007/s00213-022-06281-8},

year  = {2022},

date = {2022-12-01},

urldate = {2022-12-01},

journal = {Psychopharmacology (Berl) },

abstract = {Objectives: This study aimed to validate a repeated measures cognitive affective bias (CAB) test in a rat model of chronic stress and compare CAB with forced swim test (FST) measures.

Method: Male and female Sprague Dawley rats were trained to associate large and small rewards with scent, spatial, and tactile cues, and their response to an ambiguous tactile stimulus tested. Rats underwent weekly CAB testing for 4 weeks with no intervention, or for 2 weeks of chronic restraint stress (CRS), followed by 2 weeks of fluoxetine, vehicle, or no treatment. CRS rats also underwent the FST at selected timepoints.},

note = {University of Western Australia},

keywords = {Rats},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Effects of an enhanced acoustic environment on residual hearing following chronic cochlear implantation and electrical stimulation in the partially deafened cat},

author = {Wise, AK., Atkinson, P, Fallon, J.B.},

url = {https://www.sciencedirect.com/science/article/pii/S0378595522002039?via%3Dihub},

doi = {https://doi.org/10.1016/j.heares.2022.108635},

year  = {2022},

date = {2022-12-01},

urldate = {2022-12-01},

journal = {Hearing Research},

volume = {426},

note = {The Bionics Institute, University of Melbourne Royal Victorian Eye and Ear Hospital},

keywords = {cats, kittens},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Optogenetic restoration of high sensitivity vision with bReaChES, a red-shifted channelrhodopsin},

author = {Lay Khoon Too, Weiyong Shen, Dario A. Protti, Atomu Sawatari, Dylan A. Black, Catherine A. Leamey, Jin Y. Huang, So-Ra Lee, Ashish E. Mathai, Leszek Lisowski, John Y. Lin, Mark C. Gillies & Matthew P. Simunovic },

doi = {https://doi.org/10.1038/s41598-022-23572-4},

year  = {2022},

date = {2022-11-11},

urldate = {2022-11-11},

journal = {Nature - Scientific Reports},

volume = {12},

number = {19312},

note = {University of Sydney},

keywords = {Mice},

pubstate = {published},

tppubtype = {article}

}

@article{,

title = {Orientation pinwheels in primary visual cortex of a highly visual marsupial},

author = {Young Jun Jung, Ali Almasi, Shi H. Sun, Molis Yunzab, Shaun L. Cloherty,

Sebastien H. Bauquier, Marilyn Renfree, Hamish Meffin, Michael R. Ibbotson},

editor = {Sci. Adv. },

doi = {doi/10.1126/sciadv.abn0954},

year  = {2022},

date = {2022-09-30},

urldate = {2022-09-30},

journal = {Science Advances},

volume = {8},

abstract = {Primary visual cortices in many mammalian species exhibit modular and periodic orientation preference maps arranged in pinwheel-like layouts. The role of inherited traits as opposed to environmental influences in determining this organization remains unclear. Here, we characterize the cortical organization of an Australian marsupial, revealing pinwheel organization resembling that of eutherian carnivores and primates but distinctly different from the simpler salt-and-pepper arrangement of eutherian rodents and rabbits. The divergence of marsupials from eutherians 160 million years ago and the later emergence of rodents and rabbits suggest that the salt-and pepper structure is not the primitive ancestral form. Rather, the genetic code that enables complex pinwheel formation is likely widespread, perhaps extending back to the common therian ancestors of modern mammals.},

note = {University of Melbourne, Wallabies},

keywords = {wallabies},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Impact of High Fat Consumption on Neurological Functions after Traumatic Brain Injury in Rats},

author = {Shannon Thomson, Yik Lung Chan, Chenju Yi Baoming Wang, Rita Machaalani, Brian G Oliver Catherine A Gorrie, Hui Chen },

url = {https://pubmed.ncbi.nlm.nih.gov/35658673/},

year  = {2022},

date = {2022-07-14},

urldate = {2022-07-14},

note = {University of Technology Sydney},

keywords = {Rats},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Sustained endosomal release of a neurokinin-1 receptor antagonist from nanostars provides long-lasting relief of chronic pain},

author = {Nicholas A. Veldhuis et al },

url = {https://research.monash.edu/en/publications/sustained-endosomal-release-of-a-neurokinin-1-receptor-antagonist},

doi = {10.1016/j.biomaterials.2022.121536},

year  = {2022},

date = {2022-06-30},

urldate = {2022-06-30},

journal = {Biomaterials },

volume = {285},

abstract = {Soft polymer nanoparticles designed to disassemble and release an antagonist of the neurokinin 1 receptor (NK1R) in endosomes provide efficacious yet transient relief from chronic pain. These micellar nanoparticles are unstable and rapidly release cargo, which may limit the duration of analgesia. We examined the efficacy of stable star polymer nanostars containing the NK1R antagonist aprepitant-amine for the treatment of chronic pain in mice. Nanostars continually released cargo for 24 h, trafficked through the endosomal system, and disrupted NK1R endosomal signaling. After intrathecal injection, nanostars accumulated in endosomes of spinal neurons. Nanostar-aprepitant reversed mechanical, thermal and cold allodynia and normalized nociceptive behavior more efficaciously than free aprepitant in preclinical models of neuropathic and inflammatory pain. Analgesia was maintained for >10 h. The sustained endosomal delivery of antagonists from slow-release nanostars provides effective and long-lasting reversal of chronic pain.},

keywords = {Mice},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Altered amyloid precursor protein, tau-regulatory proteins, neuronal numbers and behaviour, but no tau pathology, synaptic and inflammatory changes or memory deficits, at 1 month following repetitive mild traumatic brain injury},

author = {Sydney M.A. Juan, Maria Daglas, Paul A. Adlard},

doi = {10.1111/ejn.15752},

year  = {2022},

date = {2022-06-29},

urldate = {2022-06-29},

journal = {European Journal of Neuroscience},

abstract = {Repetitive mild traumatic brain injury, commonly experienced following sports injuries, results in various secondary injury processes and is increasingly recognised as a risk factor for the development of neurodegenerative conditions such as chronic traumatic encephalopathy, which is characterised by tau pathology. We aimed to characterise the underlying pathological mechanisms that might contribute to the onset of neurodegeneration and behavioural changes in the less-explored subacute (1-month) period following single or repetitive controlled cortical impact injury (five impacts, 48 h apart) in 12-week-old male and female C57Bl6 mice. We conducted motor and cognitive testing, extensively characterised the status of tau and its regulatory proteins via western blot and quantified neuronal populations using stereology. We report that r-mTBI resulted in neurobehavioural deficits, gait impairments and anxiety-like behaviour at 1 month post-injury, effects not seen following a single injury. R-mTBI caused a significant increase in amyloid precursor protein, an increased trend towards tau phosphorylation and significant changes in kinase/phosphatase proteins that may promote a downstream increase in tau phosphorylation, but no changes in synaptic or neuroinflammatory markers. Lastly, we report neuronal loss in various brain regions following both single and repeat injuries. We demonstrate herein that repeated impacts are required to promote the initiation of a cascade of biochemical events that are consistent with the onset of neurodegeneration subacutely post-injury. Identifying the timeframe in which these changes occur and the pathological mechanisms involved will be crucial for the development of future therapeutics to prevent the onset or mitigate the progression of neurodegeneration following r-mTBI.},

note = {The Florey Institute of Neuroscience & Mental Health, The Melbourne Dementia Research Centre, the University of Melbourne.},

keywords = {Mice},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = { Replicating infant-specific reactive astrocyte functions in the injured adult brain},

author = {Leon Teo, Anthony G Boghdadi, Jihane Homman-Ludiye, Inaki-Carril Mundinano, William C Kwan, James A Bourne},

url = {https://pubmed.ncbi.nlm.nih.gov/34147584/},

doi = {10.1016/j.pneurobio.2021.102108},

year  = {2022},

date = {2022-06-17},

urldate = {2022-06-17},

abstract = {Infants and adults respond differently to brain injuries. Specifically, improved neuronal sparing along with reduced astrogliosis and glial scarring often observed earlier in life, likely contributes to improved long-term outcomes. Understanding the underlying mechanisms could enable the recapitulation of neuroprotective effects, observed in infants, to benefit adults after brain injuries. We reveal that in primates, Eph/ ephrin signaling contributes to age-dependent reactive astrocyte behavior. Ephrin-A5 expression on astrocytes was more protracted in adults, whereas ephrin-A1 was only expressed on infant astrocytes. Furthermore, ephrin-A5 exacerbated major hallmarks of astrocyte reactivity via EphA2 and EphA4 receptors, which was subsequently alleviated by ephrin-A1. Rather than suppressing reactivity, ephrin-A1 signaling shifted astrocytes towards GAP43+ neuroprotection, accounting for improved neuronal sparing in infants. Reintroducing ephrin-A1 after middle-aged focal ischemic injury significantly attenuated glial scarring, improved neuronal sparing and preserved circuitry. Therefore, beneficial infant mechanisms can be recapitulated in adults to improve outcomes after CNS injuries.},

note = {Monash University},

keywords = {Marmosets, Non-human primates},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Xenotransplantation of Genetically Modified Neonatal Pig Islets Cures Diabetes in Baboons},

author = {Hawthorn, WJ et al},

doi = {https://doi.org/10.3389/fimmu.2022.898948},

year  = {2022},

date = {2022-06-16},

urldate = {2023-06-16},

journal = {Frontiers in Immunology},

volume = {13},

abstract = {Xenotransplantation using porcine donors is rapidly approaching clinical applicability as an alternative therapy for treatment of many end-stage diseases including type 1 diabetes. Porcine neonatal islet cell clusters (NICC) have normalised blood sugar levels for relatively short periods in the preclinical diabetic rhesus model but have met with limited success in the stringent baboon model. Here we report that NICC from genetically modified (GM) pigs deleted for αGal and expressing the human complement regulators CD55 and CD59 can cure diabetes long-term in immunosuppressed baboons, with maximum graft survival exceeding 22 months. Five diabetic baboons were transplanted intraportally with 9,673 – 56,913 islet equivalents (IEQ) per kg recipient weight. Immunosuppression consisted of T cell depletion with an anti-CD2 mAb, tacrolimus for the first 4 months, and maintenance with belatacept and anti-CD154; no anti-inflammatory treatment or cytomegalovirus (CMV) prophylaxis/treatment was given. This protocol was well tolerated, with all recipients maintaining or gaining weight. Recipients became insulin-independent at a mean of 87 ± 43 days post-transplant and remained insulin-independent for 397 ± 174 days. Maximum graft survival was 675 days. Liver biopsies showed functional islets staining for all islet endocrine components, with no evidence of the inflammatory blood-mediated inflammatory reaction (IBMIR) and minimal leukocytic infiltration. The costimulation blockade-based immunosuppressive protocol prevented an anti-pig antibody response in all recipients. In conclusion, we demonstrate that genetic modification of the donor pig enables attenuation of early islet xenograft injury, and in conjunction with judicious immunosuppression provides excellent long-term function and graft survival in the diabetic baboon model.},

note = {Westmead Institute for Medical Research, NSW.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}