Effect of Cold Preservation on Chronic Rejection in a Rat Hindlimb Transplantation Model

Bonastre, Jorge; Landín, Luis; Bolado, Pedro; Casado-Pérez, César; López-Collazo, Eduardo; Díez, Jesús

doi:10.1097/prs.0000000000002461

Cited by 6 publications

(12 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our results confirm these propositions and underline the importance of CD4 positive cells in CR reactions. Furthermore, we confirmed preliminary studies, who could also demonstrate CD4 and CD68 positive cell immigration [6,27,28]. However, CD68 only reached significant difference between the CR and the Iso group.…”

Section: Plos Onesupporting

confidence: 90%

“…Previous works also detected elevated levels of IL6 in experimental VCA models [27,28], but to our knowledge, a specific correlation between IL6 elevation and CR has not been shown and IL6-inhibitors have not yet been applied in VCA. Besides IL6, TNF is also a potent cytokine and nuclear factor κB dependent, which finally leads to T-cell development and proliferation [35].…”

Section: Plos Onementioning

confidence: 55%

See 1 more Smart Citation

A chronic rejection model and potential biomarkers for vascularized composite allotransplantation

et al. 2020

View full text Add to dashboard Cite

Background Chronic rejection remains the Achilles heel in vascularized composite allotransplantation. Animal models to specifically study chronic rejection in vascularized composite allotransplantation do not exist so far. However, there are established rat models to study chronic rejection in solid organ transplantation such as allogeneic transplantation between the rat strains Lewis and Fischer344. Thus, we initiated this study to investigate the applicability of hindlimb transplantation between these strains to imitate chronic rejection in vascularized composite allotransplantation and identify potential markers. Methods Allogeneic hindlimb transplantation were performed between Lewis (recipient) and Fischer344 (donor) rats with either constant immunosuppression or a high dose immunosuppressive bolus only in case of acute skin rejections. Histology, immunohistochemistry, microarray and qPCR analysis were used to detect changes in skin and muscle at postoperative day 100. Results We were able to demonstrate significant intimal proliferation, infiltration of CD68 and CD4 positive cells, up-regulation of inflammatory cytokines and initiation of muscular fibrosis in the chronic rejection group. Microarray analysis and subsequent qPCR identified CXC ligands 9-11 as potential markers of chronic rejection.

show abstract

Section: Plos Onesupporting

confidence: 90%

Section: Plos Onementioning

confidence: 55%

A chronic rejection model and potential biomarkers for vascularized composite allotransplantation

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Detrimental effects of cold storage have also been substantiated on experimental VCA models. 3,4 A strong correlation between the duration of cold ischemia and extent of chronic rejection was demonstrated on rat hindlimb allografts. Although the investigation of the mechanism of cold storage injury in limb allografts is beyond the scope of this study, it is plausible that formation of reactive oxygen species and the resultant oxidative stress may have played a role in the axonal loss and structural muscle injury.…”

Section: Discussionmentioning

confidence: 97%

“…reperfusion phase, resulting in an increased incidence of acute and chronic rejection episodes, and organ failures. 3,4 In hand allografts, the critical time of cold ischemia resulting in permanent damage is currently unknown. According to the international hand transplantation registry, cold ischemia times ranged from 30 minutes to 13.5 hours (average 5.5 hours) in hand allografts.…”

mentioning

confidence: 99%

Effect of Static Cold Storage on Skeletal Muscle after Vascularized Composite Tissue Allotransplantation

Gok

Kubiak

Guy

et al. 2019

J Reconstr Microsurg

View full text Add to dashboard Cite

Background Prolonged cold ischemia associated with static cold storage (SCS) results in higher incidence of acute and chronic allograft rejection in solid organ transplantations. Deleterious effects of SCS on vascularized composite tissue allograft were studied with limited data on muscle structure and function. The aim of this study is to evaluate the long-term impact of SCS on muscle metabolism, structure, and force generation using a syngeneic rat hindlimb transplantation model. Methods Sixty-five male Lewis rats (250 ± 25 g) were distributed into five groups, including naive control, sciatic nerve denervation/repair, immediate transplantation, transplantation following static warm storage for 6 hours at room temperature, and transplantation following SCS for 6 hours at 4°C. Sciatic nerves were repaired in all transplantations. Muscle samples were taken for histology and metabolomics analysis following electromyography and muscle force measurements at 12 weeks after transplantation. Results All cold-preserved limbs remained viable at 12 weeks, whereas animals receiving limbs preserved in room temperature had no survivors. The SCS transplantation group showed a 73% injury score, significantly higher than groups receiving immediate transplants without cold preservation (50%, p < 0.05). A significant decline in muscle contractile force was also demonstrated in comparison to the immediate transplantation group (p < 0.05). In the SCS group, muscle energy reserves remained relatively well preserved in surviving fibers. Conclusion SCS extends allograft survival but fails to preserve muscle structure and force.

show abstract

“…Other conditions associated with the transplantation procedure, namely cold preservation as compared to normothermic preservation, favored CR in experimental hindlimb transplants with sub-optimal immunosuppression. 38 Although not the main scope of this study, we evaluated the presence of antibodies in relation to the functional outcome. The results indicate trends towards a difference in functional outcome over time.…”

Section: A C C E P T E Dmentioning

confidence: 99%

Clinical Significance of Alloantibodies in Hand Transplantation: A Multicenter Study

et al. 2019

View full text Add to dashboard Cite

Background. Donor-specific antibodies (DSAs) have a strong negative correlation with long-term survival in solid organ transplantation. Although the clinical significance of DSA and antibody-mediated rejection (AMR) in upper extremity transplantation (UET) remains to be established, a growing number of single-center reports indicate their presence and potential clinical impact. Methods. We present a multicenter study assessing the occurrence and significance of alloantibodies in UET in reference to immunological parameters and functional outcome. Results. Our study revealed a high prevalence and early development of de novo DSA and non-DSA (43%, the majority detected within the first 3 postoperative y). HLA class II mismatch correlated with antibody development, which in turn significantly correlated with the incidence of acute cellular rejection. Cellular rejections preceded antibody development in almost all cases. A strong correlation between DSA and graft survival or function cannot be statistically established at this early stage but a correlation with a lesser outcome seems to emerge. Conclusions. While the phenotype and true clinical effect of AMR remain to be better defined, the high prevalence of DSA and the correlation with acute rejection highlight the need for optimizing immunosuppression, close monitoring, and the relevance of an HLA class II match in UET recipients.

show abstract

Effect of Cold Preservation on Chronic Rejection in a Rat Hindlimb Transplantation Model

Cited by 6 publications

References 58 publications

A chronic rejection model and potential biomarkers for vascularized composite allotransplantation

A chronic rejection model and potential biomarkers for vascularized composite allotransplantation

Effect of Static Cold Storage on Skeletal Muscle after Vascularized Composite Tissue Allotransplantation

Clinical Significance of Alloantibodies in Hand Transplantation: A Multicenter Study

Contact Info

Product

Resources

About