The Role of Xenotransplantation in Cardiac Transplantation

Salvatore, Sergio De; Segreto, Antonio; Chiusaroli, Alessandro; Congiu, Stefano; Bizzarri, Federico

doi:10.1111/jocs.12454

Cited by 10 publications

(8 citation statements)

References 50 publications

(68 reference statements)

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“…Third, genome editing in animals could provide a solution to the long-standing shortage of human organ donors by facilitating xenotransplantation from pigs into humans [ [26,39,51,64,66,68,73,74,76,77,130,135,140]. It was mentioned that this solution should be compared to alternative solutions to this problem in terms of resource allocation and prioritization [105].…”

Section: Human Healthmentioning

confidence: 99%

The ethics of genome editing in non-human animals: a systematic review of reasons reported in the academic literature

Graeff

Jongsma

Johnston

et al. 2019

Phil. Trans. R. Soc. B

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One contribution of 17 to a discussion meeting issue 'The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems'.In recent years, new genome editing technologies have emerged that can edit the genome of non-human animals with progressively increasing efficiency. Despite ongoing academic debate about the ethical implications of these technologies, no comprehensive overview of this debate exists. To address this gap in the literature, we conducted a systematic review of the reasons reported in the academic literature for and against the development and use of genome editing technologies in animals. Most included articles were written by academics from the biomedical or animal sciences. The reported reasons related to seven themes: human health, efficiency, risks and uncertainty, animal welfare, animal dignity, environmental considerations and public acceptability. Our findings illuminate several key considerations about the academic debate, including a low disciplinary diversity in the contributing academics, a scarcity of systematic comparisons of potential consequences of using these technologies, an underrepresentation of animal interests, and a disjunction between the public and academic debate on this topic. As such, this article can be considered a call for a broad range of academics to get increasingly involved in the discussion about genome editing, to incorporate animal interests and systematic comparisons, and to further discuss the aims and methods of public involvement.This article is part of a discussion meeting issue 'The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems'.Data accessibility. This article has no additional data.

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Section: Human Healthmentioning

confidence: 99%

The ethics of genome editing in non-human animals: a systematic review of reasons reported in the academic literature

Graeff

Jongsma

Johnston

et al. 2019

Phil. Trans. R. Soc. B

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“…To the best of the authors’ knowledge, there are currently no commercially available porcine-derived bone graft products available for clinical use in orthopaedic surgery and there are no clinical reports of porcine bone grafting into human subjects in the orthopaedic literature. Porcine species share similar anatomy, physiology, and genetic makeup with human species [ 14 , 17 ] and historically have served as excellent xenograft donors to human recipients [ 22 , 23 , 24 ]. While orthopaedic literature has limited reports of xenograft use, facial reconstruction and periodontal literature has more experience with these products [ 25 , 26 , 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

A Decellularized Porcine Xenograft-Derived Bone Scaffold for Clinical Use as a Bone Graft Substitute: A Critical Evaluation of Processing and Structure

Bracey

Seyler

Jinnah

et al. 2018

JFB

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Background: Bone grafts are used in approximately one half of all musculoskeletal surgeries. Autograft bone is the historic gold standard but is limited in supply and its harvest imparts significant morbidity to the patient. Alternative sources of bone graft include allografts, synthetics and, less commonly, xenografts which are taken from animal species. Xenografts are available in unlimited supply from healthy animal donors with controlled biology, avoiding the risk of human disease transmission, and may satisfy current demand for bone graft products. Methods: In the current study, cancellous bone was harvested from porcine femurs and subjected to a novel decellularization protocol to derive a bone scaffold. Results: The scaffold was devoid of donor cellular material on histology and DNA sampling (p < 0.01). Microarchitectural properties important for osteoconductive potential were preserved after decellularization as shown by high resolution imaging modalities. Proteomics data demonstrated similar profiles when comparing the porcine bone scaffold against commercially available human demineralized bone matrix approved for clinical use. Conclusion: We are unaware of any porcine-derived bone graft products currently used in orthopaedic surgery practice. Results from the current study suggest that porcine-derived bone scaffolds warrant further consideration to serve as a potential bone graft substitute.

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“…Xenograft‐derived bone products are currently not FDA approved for use in any orthopedic surgery application. Nearly, all clinical results have been reported with bovine‐derived bone, but our laboratory is currently considering use of porcine‐derived bone 11,51 because porcine species share similar anatomy, organ size, physiology, and genetic makeup with human species and have a successful history with porcine cardiac tissue transplantation into humans 20,52‐55 . We used a published decellularization and tissue oxidation protocol 56‐61 to derive bone scaffolds from the cancellous bone found in the distal metaphyseal region of porcine femurs (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…Bone grafting continues to play a critical role in orthopedic surgery practice with significant clinical and financial implications for bovine-derived bone, but our laboratory is currently considering use of porcine-derived bone 11,51 because porcine species share similar anatomy, organ size, physiology, and genetic makeup with human species and have a successful history with porcine cardiac tissue transplantation into humans. 20,[52][53][54][55] We used a published decellularization and tissue oxidation protocol [56][57][58][59][60][61] to derive bone scaffolds from the cancellous bone found in the distal metaphyseal region of porcine femurs (Figure 2). 51 Using this decellularization technique, we were able to remove 98% of host DNA content and 98.5% of the alpha-Gal epitope from donor bone in pre-clinical studies.…”

Section: Con Clus I On S and Future Direc Tionsmentioning

confidence: 99%

Bone xenotransplantation: A review of the history, orthopedic clinical literature, and a single‐center case series

Bracey

Cignetti

Jinnah

et al. 2020

Xenotransplantation

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Background: One-half of all orthopedic surgeries require bone grafting for successful outcomes in fusions, reconstructive procedures, and the treatment of osseous defects resulting from trauma, tumor, infection, or congenital deformity. Autologous bone grafts are taken from the patient's own body and remain the "gold standard" graft choice but are limited in supply and impart significant patient morbidity. Xenograft bone is an attractive alternative from donors with controlled biology, in large supply and at a theoretically lower cost. Clinical results with xenograft bone for orthopedic applications have been mixed in the limited clinical trials published. Methods: In the current review, we introduce fundamental principles of bone grafting, systematically review all orthopedic clinical studies reporting outcomes on patients transplanted with xenograft bone, and we present our own clinical results from patients grafted with bovine bone in foot and ankle reconstructive procedures. Results: Thirty-one clinical studies were identified for review and the majority (47%) were from spine surgery literature. Favorable results were reported in 44% of studies while 47% of studies reported poor outcomes and discouraged use of xenograft bone products. In our own clinical series, xenograft failed to integrate with host bone in 58% of cases and persistent pain was reported in 83% of cases. Conclusions: This is the first systematic review of clinical results reported after bone xenotransplantation for orthopaedic surgery applications. Current literature does not support the use of xenograft bone products and our institution's results are consistent with this conclusion. Our laboratory has reported promising pre-clinical results with a xenograft product derived from porcine cancellous bone, but additional testing is required before considering clinical translation.

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The Role of Xenotransplantation in Cardiac Transplantation

Abstract: This review will discuss the history and development of the field of genetic modification, up to the most recent scientific discoveries, and will also consider the current uses of genetic therapy.

Cited by 10 publications

References 50 publications

The ethics of genome editing in non-human animals: a systematic review of reasons reported in the academic literature

The ethics of genome editing in non-human animals: a systematic review of reasons reported in the academic literature

A Decellularized Porcine Xenograft-Derived Bone Scaffold for Clinical Use as a Bone Graft Substitute: A Critical Evaluation of Processing and Structure

Bone xenotransplantation: A review of the history, orthopedic clinical literature, and a single‐center case series

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