Composite tissue allotransplantation in newborns: A swine model

Solla, Federico; Pan, Hua; Watrelot, Dorothée; Leveneur, Olivia; Dubernard, Jean‐Michel; Gazarian, Aram

doi:10.1016/j.jss.2012.01.030

Cited by 19 publications

(6 citation statements)

References 17 publications

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“…Cefazolin was the most commonly prescribed drug; its administration alone or in combination with other antimicrobials being described in 22 of 233 (9 per cent) articles. Intraoperative cephalosporin use followed by a prophylactic antimicrobial course with penicillin (and in one case with additional enrofloxacin) was reported in three articles describing an orthopaedic procedure (Solla and others 2013), laparotomy (Li and others 2012) and tracheal transplantation (Haykal and others 2013), respectively.…”

Section: Resultsmentioning

confidence: 99%

Prophylactic use of antimicrobials in surgical pig models; a literature review (2012‐2014)

et al. 2015

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There are no guidelines for antimicrobial use in experimental animals even though appropriate selection is required to reduce risk of surgical site infection (SSI) and resistance development. Pigs are used extensively as experimental surgical models for people. This review compares reported antimicrobial prescription in recently published pig surgical studies (retrieved by PubMed, Web of Knowledge and Google Scholar) with human guidelines for prophylactic antimicrobial use (National Institute of Clinical Excellence and the American Society of Health-System Pharmacists). A five-point appropriate antimicrobial use index (AAUI), based on aforementioned guidelines, was used to grade 233 studies. Use of World Health Organization-designated critically important antimicrobials (CIA) was recorded. Antimicrobial use was described in 111 of 233 (48 per cent) papers. AAUI scores of 5 (maximal compliance) and 0 (no compliance) were awarded to 34 (15 per cent) and 101 (43 per cent) articles. Where reported, prophylactic antimicrobials were mostly administered after surgery (62/95, 65 per cent) and intramuscularly (36/72, 50 per cent). CIAs were described in 21 of 111 (19 per cent) papers and SSIs in 21 of 233 (9 per cent). Reported antimicrobial prophylaxis in experimental pig surgery deviates from human clinical guidelines. This has implications for antimicrobial resistance, study quality and animal welfare. Until species-specific guidelines are formulated, experimental surgical studies involving animals would probably benefit from adherence to human guidelines.

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Section: Resultsmentioning

confidence: 99%

Prophylactic use of antimicrobials in surgical pig models; a literature review (2012‐2014)

et al. 2015

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“…Knee allotransplantations in dogs were reported over 20 years ago, but these were proof-of-principle reports lacking surgical details and radiological follow-up (19,32). The focus then shifted towards heterotopic swine hind limb and porcine orthotopic forelimb models, which are currently widely used in VCA research (33)(34)(35). It appears to be more challenging to establish joint-specific large animal models for JA compared to whole limb allotransplantations.…”

Section: Referencesmentioning

confidence: 99%

Challenges and opportunities in vascularized composite allotransplantation of joints: a systematic literature review

et al. 2023

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BackgroundJoint allotransplantation (JA) within the field of vascularized composite allotransplantation (VCA) holds great potential for functional and non-prosthetic reconstruction of severely damaged joints. However, clinical use of JA remains limited due to the immune rejection associated with all forms of allotransplantation. In this study, we aim to provide a comprehensive overview of the current state of JA through a systematic review of clinical, animal, and immunological studies on this topic.MethodsWe conducted a systematic literature review in accordance with the PRISMA guidelines to identify relevant articles in PubMed, Cochrane Library, and Web of Science databases. The results were analyzed, and potential future prospects were discussed in detail.ResultsOur review included 14 articles describing relevant developments in JA. Currently, most JA-related research is being performed in small animal models, demonstrating graft survival and functional restoration with short-term immunosuppression. In human patients, only six knee allotransplantations have been performed to date, with all grafts ultimately failing and a maximum graft survival of 56 months.ConclusionResearch on joint allotransplantation has been limited over the last 20 years due to the rarity of clinical applications, the complex nature of surgical procedures, and uncertain outcomes stemming from immune rejection. However, the key to overcoming these challenges lies in extending graft survival and minimizing immunosuppressive side effects. With the emergence of new immunosuppressive strategies, the feasibility and clinical potential of vascularized joint allotransplantation warrants further investigation.

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“…Although human newborns have a large percentage of CD45RA + naive T cells but few memory T cells, as well as a higher percentage of CD4 + helper T cells and lower percentage of CD8 + cytotoxic T cells ( 55 – 59 ), these T cells showed normal in vivo responses to allogeneic stimulators, through both T cell proliferation and cytokine production. In one of our experimental studies, newborn pigs could effectively mount acute rejection to composite tissue allograft (containing bone, muscle, and skin components) on days 4–8 after transplantation ( 60 ). However, fewer memory T cells in newborn recipients may be beneficial for transplantation ( 61 ), since T cell memory is a great obstacle to tolerance induction.…”

Section: Advantages Of Tolerance Induction In Human Neonatesmentioning

confidence: 99%

Transplant Tolerance Induction in Newborn Infants: Mechanisms, Advantages, and Potential Strategies

et al. 2016

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Although several tolerance induction protocols have been successfully implemented in adult renal transplantation, no tolerance induction approach has, as yet, been defined for solid organ transplantations in young infants. Pediatric transplant recipients have a pressing demand for the elaboration of tolerance induction regimens. Indeed, since they display a longer survival time, they are exposed to a higher level of risks linked to long-term immunosuppression (IS) and to chronic rejection. Interestingly, central tolerance induction may be of great interest in newborns, because of their immunological immaturity and the important role of the thymus at this early stage in life. The present review aims to clarify mechanisms and strategies of tolerance induction in these immunologically premature recipients. We first introduce the discovery and mechanisms of neonatal tolerance in murine experimental models and subsequently analyze tolerance induction in human newborn infants. Hematopoietic mixed chimerism in neonates is also discussed based on in utero hematopoietic stem cell (HSC) transplant studies. Then, we review the recent advances in tolerance induction approaches in adults, including the infusion of HSCs associated with less toxic conditioning regimens, regulatory T cells/facilitating cells/mesenchymal stem cells transplantation, costimulatory blockade, and thymus manipulation. Finally, IS withdrawal in pediatric solid organ transplant is discussed. In conclusion, the establishment of transplant tolerance induction in infants is promising and deserves further investigations. Future studies could focus on the selection of patients, on less toxic conditioning regimens, and on biomarkers for IS minimization or withdrawal.

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Composite tissue allotransplantation in newborns: A swine model

Cited by 19 publications

References 17 publications

Prophylactic use of antimicrobials in surgical pig models; a literature review (2012‐2014)

Prophylactic use of antimicrobials in surgical pig models; a literature review (2012‐2014)

Challenges and opportunities in vascularized composite allotransplantation of joints: a systematic literature review

Transplant Tolerance Induction in Newborn Infants: Mechanisms, Advantages, and Potential Strategies

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