CRISPR/Cas Technology in Pig-to-Human Xenotransplantation Research

Ryczek, Natalia; Hryhorowicz, Magdalena; Zeyland, Joanna; Lipiński, Daniel; Słomski, R.

doi:10.3390/ijms22063196

Cited by 34 publications

(32 citation statements)

References 164 publications

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“…However, xenogeneic transplantation from pigs to humans is compromised by high immune incompatibility and a complex rejection process. However, the rapid development of genetic engineering techniques enables genome modifications in pigs that reduce the cross-species immune barrier (Ryczek et al 2021 ). Xenotransplantation is a multidisciplinary undertaking, requiring the development of a range of research methods.…”

Section: Discussionmentioning

confidence: 99%

Porcine ovarian cortex-derived putative stem cells can differentiate into endothelial cells in vitro

Wartalski

Gorczyca

Wiater

et al. 2021

Histochem Cell Biol

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Endothelial cells (ECs), the primary component of the vasculature, play a crucial role in neovascularization. However, the number of endogenous ECs is inadequate for both experimental purposes and clinical applications. Porcine ovarian putative stem cells (poPSCs), although not pluripotent, are characterized by great plasticity. Therefore, this study aimed to investigate whether poPSCs have the potential to differentiate into cells of endothelial lineage. poPSCs were immunomagnetically isolated from postnatal pig ovaries based on the presence of SSEA-4 protein. Expression of mesenchymal stem cells (MSCs) markers after pre-culture, both at the level of mRNA: ITGB1, THY, and ENG and corresponding protein: CD29, CD90, and CD105 were significantly higher compared to the control ovarian cortex cells. To differentiate poPSCs into ECs, inducing medium containing vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF), epidermal growth factor (EGF), ascorbic acid, and heparin was applied. After 14 days, poPSC differentiation into ECs was confirmed by immunofluorescence staining for vascular endothelial cadherin (VECad) and vascular endothelial growth factor receptor-2 (VEGFR-2). Semi-quantitative WB analysis of these proteins confirmed their high abundance. Additionally, qRT-PCR showed that mRNA expression of corresponding marker genes: CDH5, KDR was significantly higher compared with undifferentiated poPSCs. Finally, EC functional status was confirmed by the migration test that revealed that they were capable of positive chemotaxis, while tube formation assay demonstrated their ability to develop capillary networks. In conclusion, our results provided evidence that poPSCs may constitute the MSC population in the ovary and confirmed that they might be a potential source of ECs for tissue engineering.

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Section: Discussionmentioning

confidence: 99%

Porcine ovarian cortex-derived putative stem cells can differentiate into endothelial cells in vitro

Wartalski

Gorczyca

Wiater

et al. 2021

Histochem Cell Biol

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“…Gene editing combined with SCNT has been achieved in both species (Liu et al, 2018b;Yan et al, 2018;Zhou et al, 2015). The advantage of SCNT is that the animals produced by this technology are consistent without mosaics (Ryczek et al, 2021). For large animals, Figure 2 Animal models produced by different methods.…”

Section: Somatic Cell Nuclear Transfermentioning

confidence: 99%

“…They found that the mouse had decreased plasma levels of PCSK9. (Butler et al, 2016;Fischer et al, 2020;Fu et al, 2020;Ladowski et al, 2019;Ryczek et al, 2021). In the future, the "ideal" modified pig could be produced with advanced geneediting technology for the benefit of patients.…”

Section: Cardiovascular Diseasementioning

confidence: 99%

Gene editing and its applications in biomedicine

Zhuang

et al. 2022

Sci. China Life Sci.

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The steady progress in genome editing, especially genome editing based on the use of clustered regularly interspaced short palindromic repeats (CRISPR) and programmable nucleases to make precise modifications to genetic material, has provided enormous opportunities to advance biomedical research and promote human health. The application of these technologies in basic biomedical research has yielded significant advances in identifying and studying key molecular targets relevant to human diseases and their treatment. The clinical translation of genome editing techniques offers unprecedented biomedical engineering capabilities in the diagnosis, prevention, and treatment of disease or disability. Here, we provide a general summary of emerging biomedical applications of genome editing, including open challenges. We also summarize the tools of genome editing and the insights derived from their applications, hoping to accelerate new discoveries and therapies in biomedicine.

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“…Thus, there are numerous genetically‐modified pig models currently available in xenotransplantation research each with their own demonstrated benefits. For a comprehensive review of these models, we direct readers to recently published reviews in the field 23,45 …”

Section: Immune Rejection Of Xenograftsmentioning

confidence: 99%

Designer organs: The future of personalized transplantation

Buchwald

Martins

2022

Artificial Organs

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Organ transplantation is the definitive treatment for end‐stage solid organ diseases, yet biological and logistical barriers reduce the rate of successful organ transplants. As such, there is a need for gene therapy and gene modulation strategies in the organ transplantation setting to prevent rejection, expand the donor pool of available organs, and attenuate ischemia‐reperfusion damage. As we are entering an era of “precision medicine,” the organ transplant field is becoming equipped with the tools necessary to personalize and optimize organs designed specifically to withstand injurious pathways that occur during transplantation, such that the concept of “designer organs” will be a reality in the near future. In this review, we highlight the recent progress using gene knockout and knock‐in strategies used mainly in the context of xenotransplantation. We also discuss advancements in CRISPR‐Cas9 gene editing and RNA interference in relation to organ transplantation. Lastly, we discuss the exciting future implications of customized gene therapy in the transplantation setting, and its ability to potentially create a future where organs intended for transplant are personalized to maximize both graft and patient survival.

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CRISPR/Cas Technology in Pig-to-Human Xenotransplantation Research

Cited by 34 publications

References 164 publications

Porcine ovarian cortex-derived putative stem cells can differentiate into endothelial cells in vitro

Porcine ovarian cortex-derived putative stem cells can differentiate into endothelial cells in vitro

Gene editing and its applications in biomedicine

Designer organs: The future of personalized transplantation

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