Progress in xenotransplantation: overcoming immune barriers

Sykes, Megan; Sachs, David H.

doi:10.1038/s41581-022-00624-6

Cited by 58 publications

(36 citation statements)

References 245 publications

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“…Xenotransplantion has been notorious for very high rates of failures when it was first suggested. The discovery of the Gal epitope and the finding of the concordant and discordant species was a serious advancement in the field (Lei et al, 2022; Sykes & Sachs, 2022). Recently, Griffith et al reported genetically modified porcine‐to‐human cardiac xenotransplantation.…”

Section: Discussionmentioning

confidence: 99%

Composite tissue xenopreservation: Preliminary results of staged VCA in rat to mouse model

et al. 2023

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BackgroundThe time between procurement and transplantation of composite tissues, especially regarding the limited donor pool, is a challenge effecting the outcomes of the transplantation. Current preservation techniques mainly include either cold preservation with a solution or machine perfusion using blood or certain oxygen‐carrying solutions. However, none enables preservation beyond 24 h. Increasing this time to several days will provide better usage of the donor pool, safer transplantation of VCA with significant muscle content, and gives time to stabilize a patient before long surgical procedures. Herein, we described a novel strategy of xenopreservation (preservation via xenotransplantation) to preserve composite tissues for 7 days, followed by staged transplantation.Materials and MethodsWe used two concordant species, female Sprague Dawley rats (n = 10) and female CF‐1 mice (n = 10) in this study. Four of pair of animals are used for anatomical study. The groin flap of the rat was used as a xenograft and xenotransplanted to the neck area of the carrier mouse. Cyclosporine (CsA) was administered used as immunosuppressant. After 7 days of preservation on the mouse neck, xenotransplanted groin flap (called xenopreserved flap) was re‐harvested, skin and vessels samples were collected for histopathological evaluation, and the xenopreserved flap was transplanted to the donor rat's opposite groin area. Anastomoses were performed between the flap's pedicle and the femoral vessels. Clinical observation regarding inflammation and tissue perfusion of the xenopreserved flap was monitored daily. Fifteen days after the second surgical procedure, the rats were euthanized, and skin and vessel samples were collected. Histologic evaluation, including inflammatory cell numbers, was performed. Wilcoxon test was used to compare the changes in inflammation severity and p < .05 was set for statistical significance.ResultsAll xenopreserved groin flaps except one survived. Mean lymphocyte count before the second operation (at the end of the xenopreservation procedure) was 20,22 ± 0.44 and reduced to 13,14 ± 0.47 at the end of 15 days, and the difference was statistically significant (p < .05).ConclusionThis proof‐of‐concept study with preliminary results showed that xenotransplantation might be a novel strategy for preservation of VCA for a certain period of time. However, additional translational studies are needed to modulate the tissue changes following xenopreservation.

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Section: Discussionmentioning

confidence: 99%

Composite tissue xenopreservation: Preliminary results of staged VCA in rat to mouse model

et al. 2023

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“…As previously mentioned, the triple knockout (TKO) genetic background is widely accepted for human clinical trials in xenotransplantation. 13,14 The field seems to be divided into two approaches: (1) incorporating additional modifications (such as human transgenes, PERV mutations, etc.) or (2) adopting a "less is more approach," utilizing either a GTKO/hCD55 or a TKO pig.…”

Section: Genetic Modifications Of the Donormentioning

confidence: 99%

The Young Investigator Committee of the International Xenotransplantation Association—Perspective of advancements in the field in 2023

Goerlich,

Kamberi,

Ladowski

et al. 2024

Xenotransplantation

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The 2023 IXA conference, hosted in San Diego, CA, brimmed with excitement against the backdrop of recent innovations in both the pre‐clinical and clinical realms with several first‐in‐human applications of xenotransplantation. The theme, “Pigs are flying,” alluded to the adage that xenotransplantation would only become a clinical reality “when pigs fly,” suggesting a day that might never come. The event witnessed significant attendance, with 600 participants—the highest in the history of an IXA‐IPITA joint congress. Among the attendees were members of the Food and Drug Administration (FDA), the National Institutes of Health (NIH), and corporate sponsors deeply engaged in the field. We summarize the latest topics from the congress, ranging from the pros/cons of decedent models of xenotransplantation and genetic engineering of porcine heart valves, solid organs, and cells for clinical translation and their regulatory and ethical landscape.

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“…A human recipient can receive the source of cells, tissues, or organs from nonhuman animals (i. e., pig), known as xenotransplantation alleviates the shortages and provides a complementary solution of high potency for treating certain diseases, such as neurodegenerative disorders, diabetes, and heart failure. [43] One of the critical limitations of xenotransplantation is the immune rejection caused by xeno-antigens related to sugar epitopes such as galactose and Neu5Gc. [44] Genetic glycoengineering is currently a predominant strategy to remove surface carbohydrate antigens of xeno-organs and reduce their immunogenicity (Figure 3).…”

Section: Universal Donor Blood and Organmentioning

confidence: 99%

“…Despite all this, the clinical demand for transplantation far exceeds the supply, resulting in a large number of waitlist mortality. A human recipient can receive the source of cells, tissues, or organs from nonhuman animals (i. e., pig), known as xenotransplantation alleviates the shortages and provides a complementary solution of high potency for treating certain diseases, such as neurodegenerative disorders, diabetes, and heart failure [43] . One of the critical limitations of xenotransplantation is the immune rejection caused by xeno‐antigens related to sugar epitopes such as galactose and Neu5Gc [44] .…”

Section: Therapeutic Opportunities Driven By Live‐cell Glycocalyx Eng...mentioning

confidence: 99%

Live‐Cell Glycocalyx Engineering

Wang

Hong

2023

ChemBioChem

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A heavy layer of glycans forms a brush matrix bound to the outside of all the cells in our bodies; it is referred to as the “sugar forest” or glycocalyx. Beyond the increased appreciation of the glycocalyx over the past two decades, recent advances in engineering the glycocalyx on live cells have spurred the creation of cellular drugs and novel medical treatments. The development of new tools and techniques has empowered scientists to manipulate the structures and functions of cell‐surface glycans on target cells and endow target cells with desired properties. Herein, we provide an overview of live‐cell glycocalyx engineering strategies for controlling the cell‐surface molecular repertory to suit therapeutic applications, even though the realm of this field remains young and largely unexplored.

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Progress in xenotransplantation: overcoming immune barriers

Cited by 58 publications

References 245 publications

Composite tissue xenopreservation: Preliminary results of staged VCA in rat to mouse model

Composite tissue xenopreservation: Preliminary results of staged VCA in rat to mouse model

The Young Investigator Committee of the International Xenotransplantation Association—Perspective of advancements in the field in 2023

Live‐Cell Glycocalyx Engineering

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