Biomarker and surrogate development in vascularised composite allograft transplantation: Current progress and future challenges

Honeyman, Calum; Stark, Helen; Wang, Hayson Chenyu; Hester, Joanna; Issa, Fadi; Giele, Henk

doi:10.1016/j.bjps.2020.11.022

Cited by 8 publications

(8 citation statements)

References 62 publications

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“…Among the other small molecules of great relevance to allograft stratification are iNOS, ROS, Caspase-3, HMGB-1, and Necrostatin-1. The challenge is identifying readily measurable, decision-worthy small molecules that support predictive analytics [ 70 , 71 ]. These bioassay, biomedical sensor, and possibly biosensor [ 72 ] data may serve as fused inputs into stratification algorithms [ 73 ] such as multi-class linear support vector machines (SVM-L), ensemble bagged decision trees (EBDT), artificial neural network (ANN) classifiers, or possibility rule-based function approximations (PRBFA) classifiers, resulting in a single actionable output score [ 23 ] ( Figure 3 ).…”

Section: Bioimpedance For Non-invasive Tissue Evaluationmentioning

confidence: 99%

Real-Time Monitoring Using Multiplexed Multi-Electrode Bioelectrical Impedance Spectroscopy for the Stratification of Vascularized Composite Allografts: A Perspective on Predictive Analytics

et al. 2023

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Vascularized composite allotransplantation addresses injuries to complex anatomical structures such as the face, hand, and abdominal wall. Prolonged static cold storage of vascularized composite allografts (VCA) incurs damage and imposes transportation limits to their viability and availability. Tissue ischemia, the major clinical indication, is strongly correlated with negative transplantation outcomes. Machine perfusion and normothermia can extend preservation times. This perspective introduces multiplexed multi-electrode bioimpedance spectroscopy (MMBIS), an established bioanalytical method to quantify the interaction of the electrical current with tissue components, capable of measuring tissue edema, as a quantitative, noninvasive, real-time, continuous monitoring technique to provide crucially needed assessment of graft preservation efficacy and viability. MMBIS must be developed, and appropriate models explored to address the highly complex multi-tissue structures and time-temperature changes of VCA. Combined with artificial intelligence (AI), MMBIS can serve to stratify allografts for improvement in transplantation outcomes.

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Section: Bioimpedance For Non-invasive Tissue Evaluationmentioning

confidence: 99%

Real-Time Monitoring Using Multiplexed Multi-Electrode Bioelectrical Impedance Spectroscopy for the Stratification of Vascularized Composite Allografts: A Perspective on Predictive Analytics

et al. 2023

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“…Another set of studies seeks to detect rejection more expeditiously and less invasively than using the Banff classification based on biopsy results [20]. There are many ongoing preclinical rejection models to identify potential biomarkers [21,22]. Others have looked to serum tests for noninvasive biomarkers including matrix metalloproteinase 3 which may complement biopsy to stratify rejection severity [23].…”

Section: Reducing Riskmentioning

confidence: 99%

What is needed to ensure long-term sustainability for the field of vascularized composite allotransplantation?

Toyoda,

Levin

2023

Current Opinion in Organ Transplantation

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The field of vascularized composite allotransplantation (VCA) has demonstrated remarkable advances since its inception with some excellent long-term results in a variety of graft types. However, unlike solid organ transplantation, it has yet to become mainstream. We therefore discuss strategies on ensuring long-term sustainability by addressing continued clinical developments of VCA to improve the risk-to-benefit balance, importance of public support, improved policy and financial support, and need for a bridge to the future of transplant surgery. There has been headway on all fronts and collaboration among the VCA centers for centralization of data and incorporation of patient voices will be essential for continued progress.

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“…Kollar et al [ 37 ] found in a pilot study that significantly elevated serum matrix metalloproteinase three levels, as determined by enzyme-linked immunosorbent assay, were correlated with severe rejection in facial transplantation patients. Despite these findings, a recent review by Honeyman et al [ 38 ] outlined the need for a biomarker that can identify the very early stages of rejection. An assessment of VCA transplantation rejection via skin or sentinel flap is one clinical strategy for tolerance monitoring.…”

Section: Current Vca Regimens and Limitationsmentioning

confidence: 99%

Clinical and preclinical tolerance protocols for vascularized composite allograft transplantation

et al. 2021

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The field of vascularized composite allografts (VCAs) has undergone significant advancement in recent decades, and VCAs are increasingly common and accepted in the clinical setting, bringing hope of functional recovery to patients with debilitating injuries. A major obstacle facing the widespread application of VCAs is the side effect profile associated with the current immunosuppressive regimen, which can cause a wide array of complications such as infection, malignancy, and even death. Significant concerns remain regarding whether the treatment outweighs the risk. The potential solution to this dilemma would be achieving VCA tolerance, which would allow recipients to receive allografts without significant immunosuppression and its sequelae. Promising tolerance protocols are being studied in kidney transplantation; four major trials have attempted to withdraw immunosuppressive treatment with various successes. The common theme in all four trials is the use of radiation treatment and donor cell transplantation. The knowledge gained from these trials can provide valuable insight into the development of a VCA tolerance protocol. Despite similarities, VCAs present additional barriers compared to kidney allografts regarding tolerance induction. VCA donors are likely to be deceased, which limits the time for significant pre-conditioning. VCA donors are also more likely to be human leukocyte antigen–mismatched, which means that tolerance must be induced across major immunological barriers. This review also explores adjunct therapies studied in large animal models that could be the missing element in establishing a safe and stable tolerance induction method.

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Biomarker and surrogate development in vascularised composite allograft transplantation: Current progress and future challenges

Cited by 8 publications

References 62 publications

Real-Time Monitoring Using Multiplexed Multi-Electrode Bioelectrical Impedance Spectroscopy for the Stratification of Vascularized Composite Allografts: A Perspective on Predictive Analytics

Real-Time Monitoring Using Multiplexed Multi-Electrode Bioelectrical Impedance Spectroscopy for the Stratification of Vascularized Composite Allografts: A Perspective on Predictive Analytics

What is needed to ensure long-term sustainability for the field of vascularized composite allotransplantation?

Clinical and preclinical tolerance protocols for vascularized composite allograft transplantation

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