Composite tissue allotransplantation: opportunities and challenges

Iske, Jasper; Nian, Yeqi; Maenosono, Ryoichi; Maurer, Maik; Sauer, Igor M.; Tullius, Stefan G.

doi:10.1038/s41423-019-0215-3

Cited by 40 publications

(34 citation statements)

References 125 publications

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“…Skin endothelial cells express not only HLA class II, but also panels of costimulatory molecules and receptors required for the deployment and activation of T cells. The width of skin capillaries is narrower than T-cell diameter, enhancing direct endothelial-T cell communication [17,18]. Although most VCA protocols are based on SOT experience, and exogenous immunosuppression optimization limited SOT rejection to about 15%, VCA rejection rate still exceeds 80% in the first year.…”

Section: Adaptive Immune Responses In Vascularized Composite Allotran...mentioning

confidence: 99%

Vascularized composite allotransplantation versus solid organ transplantation: innate-adaptive immune interphase

Kadono¹,

Gruszynski

Azari³

et al. 2019

Current Opinion in Organ Transplantation

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Purpose of reviewVascularized composite allotransplantation (VCA), a life-enhancing treatment for patients with complex tissue defects, trauma or illness, expounds upon the foundation of solid organ transplantation (SOT), the gold standard in end-stage organ failure. As innate and adaptive immunity remain the fundamental concern, this review highlights divergent immunobiology responses in VCA and SOT recipients. Recent findingsHost innate immune activation drives peritransplant tissue ischemia-reperfusion injury (IRI). Despite the direct relationship between ischemia-reperfusion (IR)-stress and cell-mediated acute rejection, the mechanism of how IRI may affect VCA loss needs investigation. With skin grafts being highly immunogenic, the incidence of cell-mediated rejection is higher in VCA than SOT; whereas ex-vivo perfusion may exert cytoprotection against IRI in VCA and SOT. New treatment concepts, such as topical immunosuppression or cell-based tolerogenic therapies, may avoid systemic immunosuppression in VCA. Although antibody-mediated rejection is relatively rare in VCA and its disease seems to be distinct from that in SOT, little is known as to whether and how IRI may influence humoral immune rejection cascade in VCA or SOT.

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Section: Adaptive Immune Responses In Vascularized Composite Allotran...mentioning

confidence: 99%

Vascularized composite allotransplantation versus solid organ transplantation: innate-adaptive immune interphase

Kadono¹,

Gruszynski

Azari³

et al. 2019

Current Opinion in Organ Transplantation

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show abstract

“…7 Despite these advancements in the field of VCA, acute rejection within the first year continues to occur in over 80% of all upper extremity and face transplants, thus highlighting the infancy of the field and the importance of continued development to reduce these effects and improve graft functionality to facilitate widespread use of VCA. 8 VCA is particularly susceptible to ischemia-reperfusion injury (IRI) since it involves the transplantation of highly metabolically active tissues. This is known to be one of the primary determinants of tissue survival in VCA.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Preservation solutions for attenuation of ischemia–reperfusion injury in vascularized composite allotransplantation

2021

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Vascularized composite allotransplantation represents the final level of the reconstructive ladder, offering treatment options for severe tissue loss and functional deficiencies. Vascularized composite allotransplantation is particularly susceptible to ischemia–reperfusion injury and requires preservation techniques when subjected to extended storage times prior to transplantation. While static cold storage functions to reduce ischemic damage and is widely employed in clinical settings, there exists no consensus on the ideal preservation solution for vascularized composite allotransplantation. This review aims to highlight current clinical and experimental advances in preservation solution development and their critical role in attenuating ischemia–reperfusion injury in the context of vascularized composite allotransplantation.

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“…Skin is a major component of VCA grafts, and unlike other tissue components, the skin is proven to be extremely immunogenic. VCAs have a number of unique molecular, cellular, and architectural features that alter the character and intensity of rejection response . The incidence of allogeneic acute rejection in VCA exceeds 80%, which is much higher and severer than in any other organ in the field of transplantation.…”

Section: Introductionmentioning

confidence: 99%

Targeted Migration of Human Adipose-Derived Stem Cells to Secondary Lymphoid Organs Enhances Their Immunomodulatory Effect and Prolongs the Survival of Allografted Vascularized Composites

Luan

Tao

et al. 2019

Stem Cells

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The targeted delivery of therapeutic agents to secondary lymphoid organs (SLOs), which are the niches for immune initiation, provides an unprecedented opportunity for immune intolerance induction. The alloimmune rejection postvascularized composite allotransplantation (VCA) is mediated by T lymphocytes. Human adipose‐derived stem cells (hASCs) possess the superiority of convenient availability and potent immunoregulatory property, but their therapeutic results in the VCA are unambiguous thus far. Chemokine receptor 7 (CCR7) can specifically guide immune cells migrating into SLOs. There, the genes of CCR7–GFP or GFP alone were introduced into hASCs by lentivirus. hASCs/CCR7 maintained the multidifferentiation and immunoregulatory abilities, but it gained the migration capacity elicited by secondary lymphoid organ chemokine (SCL) (CCR7 ligand) in vitro. Noteworthily, intravenously infused hASCs/CCR7 targetedly relocated in the T‐cell aggression area in SLOs. In a rat VCA model, hASCs/GFP transfusion had a rare effect on the allografted vascularized composite. However, hASCs/CCR7 infusion potently prolonged the grafts’ survival time. The ameliorated pathologic exhibition and the regulated inflammatory cytokines in the peripheral blood were also observed. The altered axis of Th1/Th2 and Tregs/Th17 in SLOs may underlie the downregulated rejection response. Moreover, the proteomic examination of splenic T lymphocytes also confirmed that hASCs/CCR7 decreased the proteins related to cytokinesis, lymphocyte proliferation, differentiation, and apoptotic process. In conclusion, our present study demonstrated that targeted migration of hASCs/CCR7 to SLOs highly intensifies their in vivo immunomodulatory effect in the VCA model for the first time. We believe this SLO‐targeting strategy may improve the clinical therapeutic efficacy of hASC for allogeneic and autogenic immune disease. Stem Cells 2019;37:1581–1594

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Composite tissue allotransplantation: opportunities and challenges

Cited by 40 publications

References 125 publications

Vascularized composite allotransplantation versus solid organ transplantation: innate-adaptive immune interphase

Vascularized composite allotransplantation versus solid organ transplantation: innate-adaptive immune interphase

Preservation solutions for attenuation of ischemia–reperfusion injury in vascularized composite allotransplantation

Targeted Migration of Human Adipose-Derived Stem Cells to Secondary Lymphoid Organs Enhances Their Immunomodulatory Effect and Prolongs the Survival of Allografted Vascularized Composites

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