4.1 Review

Novel cell-based strategies for immunomodulation in vascularized composite allotransplantation

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Review Surgery

A Systematic Review of the Reported Complications Related to Facial and Upper Extremity Vascularized Composite Allotransplantation

David Milek et al.

Summary: Complications related to vascularized composite allotransplantation (VCA) are a significant source of morbidity and potential mortality. The incidence of these complications is higher than previously reported and should be strongly emphasized in the patient consent process. Strict patient selection criteria, complex preoperative evaluation, consideration of alternatives, and thorough disclosure to patients should be routinely performed prior to VCA indication.

JOURNAL OF SURGICAL RESEARCH (2023)

Article Immunology

Donor derived hematopoietic stem cell niche transplantation facilitates mixed chimerism mediated donor specific tolerance

Wensheng Zhang et al.

Summary: In this study, using rodent vascularized composite allotransplantation (VCA) models, it was demonstrated that the presence of donor-derived hematopoietic stem cell (HSC) niches in vascularized bone components facilitates long-term hematopoietic chimerism and promotes tolerance in recipients without harsh myeloablation. The transplanted donor HSC niches also contribute to the maintenance and homeostasis of stable mixed chimerism. Additionally, evidence was provided that chimeric thymus plays a role in the tolerance induced by mixed chimerism through thymic central deletion. This study suggests the potential use of vascularized donor bone with pre-engrafted HSC niches as a safe and effective strategy to induce robust and stable mixed chimerism-mediated tolerance in vascularized composite allotransplantation or solid organ transplantation recipients.

FRONTIERS IN IMMUNOLOGY (2023)

Review Biophysics

CD19 CAR-T therapy in solid organ transplant recipients: case report and systematic review

Andrew J. Portuguese et al.

Summary: Post-transplant lymphoproliferative disorder (PTLD) is a significant cause of cancer death in solid organ transplant recipients (SOTRs). CD19-targeted CAR-T cell therapy has shown effectiveness and manageable toxicity in treating relapsed or refractory (R/R) PTLD, as demonstrated by a case study of diffuse large B-cell lymphoma (DLBCL) PTLD and a literature review of PTLD cases treated with CD19 CAR-T therapy. The overall response rate was high, with kidney transplant recipients showing even better outcomes. Further research with larger datasets and prospective studies is needed to confirm these findings.

BONE MARROW TRANSPLANTATION (2023)

Article Cell & Tissue Engineering

Dystrophin Expressing Chimeric (DEC) Cell Therapy for Duchenne Muscular Dystrophy: A First-in-Human Study with Minimum 6 Months Follow-up

Ahlke Heydemann et al.

Summary: This study presents the safety and efficacy of a novel cell therapy called Dystrophin Expressing Chimeric (DEC) therapy in three DMD patients. The DEC01 therapy showed improvements in functional tests and electromyography parameters without the need for immunosuppression. It is a universal therapy that can be readministered if needed.

STEM CELL REVIEWS AND REPORTS (2023)

Review Surgery

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

Martin Kauke et al.

Summary: This study systematically reviewed immunomodulatory strategies used in preclinical VCA research over a 44-year timeframe, identifying trends in anatomical models and treatment approaches.

JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY (2022)

Review Biochemistry & Molecular Biology

Cell therapy in vascularized composite allotransplantation

Madonna Rica Anggelia et al.

Summary: Cell therapy has emerged as a promising strategy to improve allograft outcomes by modulating the immune system, reducing immunosuppressant drug dosages, and inducing allograft tolerance.

BIOMEDICAL JOURNAL (2022)

Article Immunology

Tolerance of a Vascularized Composite Allograft Achieved in MHC Class-I-mismatch Swine via Mixed Chimerism

Alexandre G. Lellouch et al.

Summary: A new adapted conditioning protocol has been developed to achieve tolerance across MHC class-I-mismatched barriers in pigs, demonstrating the first successful mixed chimerism-induced VCA tolerance in a large animal model.

FRONTIERS IN IMMUNOLOGY (2022)

Article Multidisciplinary Sciences

Central tolerance promoted by cell chimerism

Ann Zeleniak et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

Editorial Material Oncology

Successful CAR T Cell Therapy in a Heart and Kidney Transplant Recipient With Refractory PTLD

Daniel Oren et al.

Summary: Post-transplant lymphoproliferative disorder (PTLD) is a complication following solid organ transplantation that is related to immunosuppression. The incidence of PTLD, particularly EBV-negative PTLD, has increased in recent years. Despite advancements in medical therapy, outcomes for patients with refractory PTLD remain poor. CAR T cell therapy has shown effectiveness in treating refractory PTLD, but data on its use in solid organ transplant recipients and specifically heart transplantation are limited.

JACC: CARDIOONCOLOGY (2022)

Article Immunology

The intragraft vascularized bone marrow component plays a critical role in tolerance induction after reconstructive transplantation

Cheng-Hung Lin et al.

Summary: This study compared the effects of CBMT and VBM on vascularized composite tissue allograft transplantation, with VBM group showing longer allograft survival and high levels of chimerism. Additionally, low levels of circulating T cells and higher Treg/Teff ratio were maintained in VBM and high-dose CBMT recipients.

CELLULAR & MOLECULAR IMMUNOLOGY (2021)

Article Immunology

The Positive Impact of Donor Bone Marrow Cells Transplantation into Immunoprivileged Compartments on the Survival of Vascularized Skin Allografts

Arkadiusz Jundzill et al.

Summary: The study compared the tolerogenic effects of different allogeneic bone marrow transplantation delivery routes into immunoprivileged compartments under suppressive therapy, finding that intrathecal BMT resulted in the longest allograft survival and higher levels of CD4(+)/CD25(+) T cells in the peripheral blood. This transplantation method delayed rejection of fully mismatched VSA and induced robust, donor-specific chimerism.

ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS (2021)

Article Cell Biology

Exosomes from donor-derived adipose mesenchymal stem cells prolong the survival of vascularized composite allografts

Zhizhao Chen et al.

Summary: The study found that exosomes from donor-derived adipose-derived mesenchymal stem cells can prolong graft survival and suppress rejection responses. Additionally, ADMSC-exo also promotes an increase in donor cell chimerism and regulatory T cells, while decreasing CD4(+) T cells and Th1 cells in the transplantation setting.

JOURNAL OF CELLULAR PHYSIOLOGY (2021)

Article Immunology

Donor Recipient Chimeric Cells Induce Chimerism and Extend Survival of Vascularized Composite Allografts

Joanna Cwykiel et al.

Summary: The study assessed the efficacy of DRCC therapy in a rat VCA model, showing that the therapy induced long-term chimerism and extended VCA survival. DRCC introduces a novel concept of customized donor-recipient cell-based therapy supporting solid organ and VCA transplants.

ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS (2021)

Review Cell Biology

Small Extracellular Vesicles in Transplant Rejection

Justyna E. Golebiewska et al.

Summary: Small extracellular vesicles (sEV) released by human cells have the ability to stimulate or inhibit immune responses through multiple mechanisms, carrying antigens on their surface. Studies show that sEV play a role in rejection or tolerance in solid organ and tissue allotransplantation, potentially serving as biomarkers for detecting ongoing allograft rejection.
Review Surgery

Clinical and preclinical tolerance protocols for vascularized composite allograft transplantation

Jerry Huanda Yang et al.

Summary: The field of vascularized composite allografts (VCAs) has made significant advancements, but the main obstacle remains to be the side effects associated with immunosuppression. Seeking tolerance protocol appears to be the key to widespread application. However, VCAs present additional challenges compared to kidney allografts, including donor types and HLA mismatch issues.

ARCHIVES OF PLASTIC SURGERY-APS (2021)

Article Immunology

Integrating CAR T-Cell Therapy and Transplantation: Comparisons of Safety and Long-Term Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation After CAR T-Cell or Chemotherapy-Based Complete Remission in B-Cell Acute Lymphoblastic Leukemia

Yan-Li Zhao et al.

Summary: In B-ALL patients, similar clinical safety outcomes could be achieved with either CD19 CAR T-cell therapy followed by allo-HSCT or chemotherapy followed by allo-HSCT. Despite the inclusion of more patients with advanced diseases in the CAR-T group, the 4-year LFS and OS achieved with CAR T-cells followed by allo-HSCT were as remarkable as those achieved with chemotherapy followed by allo-HSCT.

FRONTIERS IN IMMUNOLOGY (2021)

Article Oncology

Sequential CD19/22 CAR T-cell immunotherapy following autologous stem cell transplantation for central nervous system lymphoma

Jiaying Wu et al.

Summary: The study treated 13 patients with CNSL using ASCT sequential CD19/22 CAR T-cell infusion. The results showed promising long-term efficacy and relatively manageable side effects of this treatment approach.

BLOOD CANCER JOURNAL (2021)

Article Cell & Tissue Engineering

Human dystrophin expressing chimeric (DEC) cell therapy ameliorates cardiac, respiratory, and skeletal muscle's function in Duchenne muscular dystrophy

Maria Siemionow et al.

Summary: Duchenne muscular dystrophy is a progressive and lethal disease caused by X-linked mutations, leading to muscular weakness and respiratory failure. Cell transplantation has shown promise in improving muscle function and lifespan in animal models of DMD.

STEM CELLS TRANSLATIONAL MEDICINE (2021)

Review Immunology

Antigen Specific Regulatory T Cells in Kidney Transplantation and Other Tolerance Settings

Min Hu et al.

Summary: Tregs play a crucial role in kidney transplantation by limiting immune activation and potentially reducing the need for immunosuppression. Studies have shown their importance in improving allo-specific Treg function in both animal and human models.

FRONTIERS IN IMMUNOLOGY (2021)

Article Immunology

Unraveling the Crucial Roles of FoxP3+ Regulatory T Cells in Vascularized Composite Allograft Tolerance Induction and Maintenance

Madonna Rica Anggelia et al.

Summary: The study found that Treg cells are crucial for inducing and maintaining tolerance in VCA transplantation, especially in the early post-transplant phase. Treg cells from tolerant recipients exhibit stronger suppressive potential and can rescue allografts from rejection.

TRANSPLANTATION (2021)

Article Immunology

Unraveling the Crucial Roles of FoxP3+ Regulatory T Cells in Vascularized Composite Allograft Tolerance Induction and Maintenance

Madonna Rica Anggelia et al.

Summary: The study demonstrates the importance of circulating Treg in inducing VCA tolerance in the early posttransplant phase, while allograft-residing Treg may play a role in maintaining tolerance. Treg could serve as a potential cellular therapeutic to enhance VCA outcomes.

TRANSPLANTATION (2021)

Article Medicine, General & Internal

Regulatory T cells for minimising immune suppression in kidney transplantation: phase I/IIa clinical trial

Andy Roemhild et al.

BMJ-BRITISH MEDICAL JOURNAL (2020)

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T-reg cell-based therapies: challenges and perspectives

Caroline Raffin et al.

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Article Multidisciplinary Sciences

Treg-inducing microparticles promote donor-specific tolerance in experimental vascularized composite allotransplantation

James D. Fisher et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

Review Surgery

From Auto- to Allotransplantation: Immunomodulatory Protocol for Hand and Arm Transplantation

W. P. Andrew Lee et al.

JOURNAL OF RECONSTRUCTIVE MICROSURGERY (2018)

Review Transplantation

Chronic rejection in vascularized composite allotransplantation

Emmanuel Morelon et al.

CURRENT OPINION IN ORGAN TRANSPLANTATION (2018)

Review Immunology

CAR T cells for infection, autoimmunity and allotransplantation

Colby R. Maldini et al.

NATURE REVIEWS IMMUNOLOGY (2018)

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Emerging role of exosomes in allorecognition and allograft rejection

Bruno Gonzalez-Nolasco et al.

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Article Dermatology

The regenerative role of adipose-derived stem cells (ADSC) in plastic and reconstructive surgery

Naghmeh Naderi et al.

INTERNATIONAL WOUND JOURNAL (2017)

Article Multidisciplinary Sciences

Modification of host dendritic cells by microchimerism-derived extracellular vesicles generates split tolerance

William Bracamonte-Baran et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2017)

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Face Transplantation: Partial Graft Loss of the First Case 10 Years Later

E. Morelon et al.

AMERICAN JOURNAL OF TRANSPLANTATION (2017)

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Tolerance induction via mixed chimerism in vascularized composite allotransplantation: is it time for clinical application?

Curtis L. Cetrulo et al.

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Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation

Riccardo Schweizer et al.

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Hand and Upper Extremity Transplantation: An Update of Outcomes in the Worldwide Experience

Jaimie T. Shores et al.

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Vascularized Composite Allograft Tolerance Across MHC Barriers in a Large Animal Model

D. A. Leonard et al.

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