Cellular Therapies for Prolongation of Composite Tissue Allograft Transplantation

Sacks, Justin M.; Horibe, Elaine K.; Lee, W.P. Andrew

doi:10.1016/j.cps.2006.10.003

Cited by 2 publications

(2 citation statements)

References 70 publications

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“…Reducing the requirements for nonspecific systemic immunosuppression and exploring methods of tolerance induction using cellular and pharmacological therapies is a critical objective of research. Vascularized composite allografts, regardless of current immunosuppressive modalities, experience episodes of rejection, especially of the highly immunogenic skin component . To improve clinical outcomes, more information must be gained about the rejection process.…”

Section: Introductionmentioning

confidence: 99%

Near-infrared lymphography as a minimally invasive modality for imaging lymphatic reconstitution in a rat orthotopic hind limb transplantation model

et al. 2013

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SummaryWider application of vascularized composite allotransplantation (VCA) is limited by the need for chronic immunosuppression. Recent data suggest that the lymphatic system plays an important role in mediating rejection. This study used near-infrared (NIR) lymphography to describe lymphatic reconstitution in a rat VCA model. Syngeneic (Lewis-Lewis) and allogeneic (Brown Norway-Lewis) rat orthotopic hind limb transplants were performed without immunosuppression. Animals were imaged pre-and postoperatively using indocyanine green (ICG) lymphography. Images were collected using an NIR imaging system. Co-localization was achieved through use of an acrylic paint/hydrogen peroxide mixture. In all transplants, ICG first crossed graft suture lines on postoperative day (POD) 5. Clinical signs of rejection also appeared on POD 5 in allogeneic transplants, with most exhibiting Grade 3 rejection by POD 6. Injection of an acrylic paint/hydrogen peroxide mixture on POD 5 confirmed the existence of continuous lymphatic vessels crossing the suture line and draining into the inguinal lymph node. NIR lymphography is a minimally invasive imaging modality that can be used to study lymphatic vessels in a rat VCA model. In allogeneic transplants, lymphatic reconstitution correlated with clinical rejection. Lymphatic reconstitution may represent an early target for immunomodulation.

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Section: Introductionmentioning

confidence: 99%

Near-infrared lymphography as a minimally invasive modality for imaging lymphatic reconstitution in a rat orthotopic hind limb transplantation model

et al. 2013

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“…However, reconstructive VCA is unlikely to become widely available until either the risk profiles of lifelong immunosuppressant drugs become more acceptable or a safe method of donor-specific VCA tolerance induction applicable to humans is devised [6, 7]. Although transplantation tolerance has been established in many experimental models and anecdotal incidents of tolerance in humans can be found in the literature, efforts to replicate the state safely and reliably in humans have proven futile [8, 9].…”

Section: Introductionmentioning

confidence: 99%

Vascularized Composite Allograft Rejection Is Delayed by Intrajejunal Treatment with Donor Splenocytes without Concomitant Immunosuppressants

Wallace

Yen

Yang

et al. 2012

Clinical and Developmental Immunology

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Background. Mucosal or oral tolerance, an established method for inducing low-risk antigen-specific hyporesponsiveness, has not been investigated in vascularized composite allograft (VCA) research. We studied its effects on recipient immune responses and VCA rejection. Methods. Lewis rats (n = 12; TREATED) received seven daily intrajejunal treatments of 5 × 107 splenocytes from semiallogeneic Lewis-Brown-Norway rats (LBN) or vehicle (n = 11; SHAM). Recipients' immune responses were assessed by mixed lymphocyte reaction (MLR) against donor antigen and controls. Other Lewis (n = 8; TREATED/VCA) received LBN hindlimb VCA and daily intrajejunal treatments of 5 × 107 LBN splenocytes, or LBN VCA without treatment (n = 5; SHAM/VCA), until VCAs rejected. Recipients' immune responses were characterised and VCAs biopsied for histopathology. Immunosuppressants were not used. Results. LBN-specific hyporesponsiveness was induced only in treated Lewis recipients. Treatment significantly reduced MLR alloreactivity, significantly reduced VCA rejection on histopathology, and significantly delayed clinical VCA rejection (P < 0.0005; TREATED/VCA mean 9.6 versus 6.0 days for SHAM/VCA). Treatment significantly increased immunosuppressive IL-10/IL-4/TGF-β production and significantly decreased proinflammatory IFN-γ/TNF-α. Conclusion. Jejunal exposure to antigen conferred donor specific hyporesponsiveness that delayed VCA rejection. This method may offer a low-risk adjunctive treatment option to help protect VCAs from rejection.

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Cellular Therapies for Prolongation of Composite Tissue Allograft Transplantation

Cited by 2 publications

References 70 publications

Near-infrared lymphography as a minimally invasive modality for imaging lymphatic reconstitution in a rat orthotopic hind limb transplantation model

Near-infrared lymphography as a minimally invasive modality for imaging lymphatic reconstitution in a rat orthotopic hind limb transplantation model

Vascularized Composite Allograft Rejection Is Delayed by Intrajejunal Treatment with Donor Splenocytes without Concomitant Immunosuppressants

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