A systematic review of immunomodulatory strategies used in skin-containing preclinical vascularized composite allotransplant models

Kauke, Martin; Safi, Ali-Farid; Palmer, William Jackson; Haug, Valentin; Kollar, Branislav; Nelms, Laurel; Tchiloemba, Bianief; Pomahač, Bohdan

doi:10.1016/j.bjps.2021.11.003

Cited by 15 publications

(32 citation statements)

References 141 publications

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“…However, in clinical VCA‚ micro/macrochimerism and a benefit in terms of allowing safe reduction of immunosuppression have not been demonstrated. 4 The Pittsburgh group attempted the infusion of donorderived bone marrow cells following VCA to induce mixed chimerism. To date, no data have been reported regarding the long-term effectiveness of this approach.…”

Section: Treg and Mixed Chimerismmentioning

confidence: 99%

“…To promote donor-specific tolerance and reduce the intensity of immunosuppressive medication in VCA, different cell- and pharmaceutical-based approaches are under investigation. 4…”

Section: Treg and Mixed Chimerismmentioning

confidence: 99%

“…However, in clinical VCA‚ micro/macrochimerism and a benefit in terms of allowing safe reduction of immunosuppression have not been demonstrated. 4…”

Section: Treg and Mixed Chimerismmentioning

confidence: 99%

“…To promote donor-specific tolerance and reduce the intensity of immunosuppressive medication in VCA, different cell-and pharmaceutical-based approaches are under investigation. 4 Unique to VCA is the component of a vascularized bone marrow compartment (often included are the jaw, ulna, and radius) that is thought to amplify the presence of donor-derived tolerance promoting chimeric cells by providing niches and a constant source of hematopoietic stem cell (HSC) expansion. 100 The strategy of amplifying hematolymphoid chimerism has been the topic of many preclinical and clinical studies.…”

Section: Treg and Mixed Chimerismmentioning

confidence: 99%

“…3 Furthermore‚ the long-term survival of the allograft can be subject to acute and chronic graft rejection in solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA), such as face, hand, penile, or abdominal wall transplants. 1,[4][5][6][7][8][9][10] Given the higher rate of diagnosed acute rejection episodes in up to 85% of VCA recipients, the link between long-term allograft survival and rejection episodes could theoretically even be more pronounced in VCA. 11 One approach to optimizing this risk-benefit ratio is the development of therapies allowing for safe reduction of immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

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Regulatory T Cells: Liquid and Living Precision Medicine for the Future of VCA

Kauke

Knoedler

et al. 2022

Transplantation

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Transplant rejection remains a challenge especially in the field of vascularized composite allotransplantation (VCA). To blunt the alloreactive immune response‚ stable levels of maintenance immunosupression are required. However‚ the need for lifelong immunosuppression poses the risk of severe side effects, such as increased risk of infection, metabolic complications, and malignancies. To balance therapeutic efficacy and medication side effects, immunotolerance promoting immune cells (especially regulatory T cells [Treg]) have become of great scientific interest. This approach leverages immune system mechanisms that usually ensure immunotolerance toward self-antigens and prevent autoimmunopathies. Treg can be bioengineered to express a chimeric antigen receptor or a T-cell receptor. Such bioengineered Treg can target specific antigens and thereby reduce unwanted off-target effects. Treg have demonstrated beneficial clinical effects in solid organ transplantation and promising in vivo data in VCAs. In this review, we summarize the functional, phenotypic, and immunometabolic characteristics of Treg and outline recent advancements and current developments regarding Treg in the field of VCA and solid organ transplantation.

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Section: Treg and Mixed Chimerismmentioning

confidence: 99%

“…To promote donor-specific tolerance and reduce the intensity of immunosuppressive medication in VCA, different cell- and pharmaceutical-based approaches are under investigation. 4…”

Section: Treg and Mixed Chimerismmentioning

confidence: 99%

“…However, in clinical VCA‚ micro/macrochimerism and a benefit in terms of allowing safe reduction of immunosuppression have not been demonstrated. 4…”

Section: Treg and Mixed Chimerismmentioning

confidence: 99%

Section: Treg and Mixed Chimerismmentioning

confidence: 99%