Effect of mixed hematopoietic chimerism on cardiac allograft survival in cynomolgus monkeys1

Kawai, Tatsuo; Cosimi, A. Benedict; Wee, S.; Houser, Stuart L.; Andrews, David; Sogawa, Hiroshi; Phelan, J.; Bosković, S; Nadazdin, O.; Abrahamian, Gregory A; Colvin, Robert B.; Sach, David H.; Madsen, Joren C.

doi:10.1097/00007890-200206150-00011

Cited by 102 publications

(82 citation statements)

References 24 publications

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“…124 Induction of hematopoietic chimerism is associated with immune tolerance and lack of CAV. 125 Chimerism found on the graft endothelia may have a protective effect against CAV. 33 However, although cell therapy research is promising, there is still a need to understand the mechanisms and long-term consequences of endothelial chimerism, as well as to characterize the impact of differentiated stem cells for vascular protection.…”

Section: Emerging New Strategies For the Prevention/treatment Of Cavmentioning

confidence: 99%

Cardiac Allograft Vasculopathy

2008

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Abstract-Cardiac allograft vasculopathy (CAV) continues to limit the long-term success of cardiac transplantation.Recent insights have underscored the fact that innate and adaptive immune responses are involved in the pathogenesis of CAV. Vascular lesions are the result of cumulative endothelial injuries induced both by alloimmune responses and by nonspecific insults (including ischemia-reperfusion injury, viral infections, and metabolic disorders) in the context of impaired repair mechanisms. Intravascular ultrasound is the most sensitive method for detection of CAV, and progressive intimal thickening in the first posttransplant year identifies patients at high risk for future cardiovascular events. Encouraging results with regard to the detection of CAV by noninvasive methods should be an incentive to apply routine noninvasive imaging during mid-to long-term follow-up. Improved immunosuppressive drugs, including mycophenolate mofetil and proliferation signal inhibitors, as well as statins (in part via immunomodulation), have beneficial effects on CAV progression, although there is still a need to confirm the impact of vasodilators in improving outcome after heart transplantation. Coronary revascularization for CAV is only palliative, with no long-term survival benefit. Three main strategies for CAV prevention are currently under investigation: inhibition of growth factors and cytokines, cell therapy, and tolerance induction. However, because individual responses to an allograft change over time, assays to monitor the recipient's immune response and individualized methods for therapeutic immune modulation are clearly needed. (Circulation. 2008;117:2131-2141.)

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Section: Emerging New Strategies For the Prevention/treatment Of Cavmentioning

confidence: 99%

Cardiac Allograft Vasculopathy

2008

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“…Therefore, deletion may contribute to the long-term allograft survival that occurs after co-stimulation blockade. Combined bone marrow and organ transplantation in conditioned recipients who were treated with a short course of various immunosuppressants (e.g., co-stimulation blockers, cyclosporine) has been shown to promote the development of robust tolerance in a number of rodent and preclinical transplant models as well as in humans (27)(28)(29)(30). Deletion in this model is mediated by peripheral as well as central mechanisms (31).…”

Section: Mechanisms Contributing To the Development Of Transplantatiomentioning

confidence: 99%

How Can We Measure Immunologic Tolerance in Humans?

Najafian

Albin²,

Newell³

2006

Journal of the American Society of Nephrology

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Prevention and treatment of allograft rejection in organ transplant recipients relies primarily on non-antigen-specific immunosuppression, with all its associated potential hazards and costs. Currently, the status of the recipient immune response is measured by monitoring pharmacologic drug levels and clinical/pathologic evaluation of graft function. Development of reliable assays that can measure accurately the status of the immune response not only would help clinicians customize the prescription of immunosuppressive drugs in individual patients but also may allow their complete withdrawal in some patients with immunologic tolerance. Furthermore, these assays would facilitate the safe evaluation of novel tolerogenic regimens. Achieving this goal has proved to be very difficult because it requires both a more in-depth understanding of complex mechanisms of tolerance and also identification of transplant patients with acquired tolerance to an allograft that can be studied. This review discusses the current understanding of tolerance mechanisms and outlines the unique and specific challenges in development of tolerance/monitoring assays in the field of transplantation. In addition, several of the most promising candidate assays are discussed in detail.

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“…Conditioning regimens used to achieve mixed chimerism and tolerance include lethal and sublethal total body irradiation (TBI) with or without thymic irradiation and anti-T cell antibodies (Ildstad & Sachs 1984;Kawai et al, 2002;Stykes 2001), www.intechopen.com TLI with and without anti-T cell antibodies (Slavin et al, 1976;Slavin et al, 1978;Slavin et al, 1977;Scandling et al, 2008 ;Hayamizu et al, 1999;Lan et al, 2000;Higuchi et al, 2002), costimulatory blockade with or without rapamycin therapy or cytoreduction (Wekerle et al, 2000;Durhan et al, 2000;Lambert et al, 2002;Graca et al, 2006), injection of naturally occurring CD4+CD25+ Treg (nTreg) cells combined with radiation cytoreduction (Golshayn et al, 2007;Wood & Sakaguchi, 2003), and chemical cytoreduction combined with thymic irradiation, and anti-T cell antibodies (Fudaba et al, 2006;Kawai et al 2008,). Although central and peripheral clonal deletion in chimeras can explain the lack of reactivity of host immune cells to donor alloantigens (Stikes 2001;Wekerle et al, 1998), host regulatory T cells that remain after cytoreduction or that are injected after cytoreduction can also play an important role in the engraftment of the donor organ and hematopoietic cells (Higushi 2002, Golshayn et al, 2007Wood & Sakaguchi 2003).…”

Section: Irradiation and Transplantsmentioning

confidence: 99%

Radiotherapy and Immunity – A Mini Review

Villar¹

2012

Immunosuppression - Role in Health and Diseases

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Effect of mixed hematopoietic chimerism on cardiac allograft survival in cynomolgus monkeys1

Cited by 102 publications

References 24 publications

Cardiac Allograft Vasculopathy

Cardiac Allograft Vasculopathy

How Can We Measure Immunologic Tolerance in Humans?

Radiotherapy and Immunity – A Mini Review

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