What question did this study set out to answer?

To determine whether pretransplant gene therapy delivering thymosin ß4 via an adeno-associated viral vector (AAV2.9) can attenuate acute rejection and prolong cardiac allograft survival.

August 22, 2014Transplantation

Adeno-Associated Viral Vector 2.9 Thymosin ß4 Application Attenuates Rejection After Heart Transplantation

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Why the study?

Does AAV2.9-mediated gene transfer of thymosin ß4 improve graft survival and attenuate rejection in a pig model of heterotopic heart transplantation?

Population

Landrace or Munich mini pigs undergoing heterotopic, abdominal transplantation of cardiac allografts

Comparison

AAV2.9.Tß4 and vascular endothelial growth… vs AAV2.9.LacZ and vascular endothelial growth…

Design

Preclinical

Authors

JPJ. PostrachLudwig-Maximilians-Universität München MSMaximilian SchmidtComprehensive Cancer Center Vienna MTMichael ThormannLudwig-Maximilians-Universität München

Discussion

Member takes

Implication

Does not support clinical adoption in transplantation; leaves open translation of Tß4 gene therapy from this pig model.

Key Points

To determine whether pretransplant gene therapy delivering thymosin ß4 via an adeno-associated viral vector (AAV2.9) can attenuate acute rejection and prolong cardiac allograft survival.
Performed heterotopic abdominal cardiac allotransplantation in Landrace and Munich mini pigs (n=5 per group).
Transduced donor hearts for 45 minutes prior to transplantation via in situ perfusion with autologous blood containing VEGF and either AAV2.9.Tß4 or control AAV2.9.LacZ.
Maintained postoperative immunosuppression for 10 days and evaluated graft survival, capillary density, histological rejection, and regional myocardial function.
AAV2.9.Tß4 gene transfer significantly prolonged graft survival compared to control (31±4 days with AAV2.9.Tß4 vs. 10±3 days with AAV2.9.LacZ).
Regional myocardial function was significantly improved in mini pigs receiving Tß4 compared to control (subendocardial segment shortening of 15.8%±2.3% in AAV2.9.Tß4 vs. 9.1%±0.9% in AAV2.9.LacZ).
Tß4 overexpression attenuated inflammation, necrosis, and acute vascular rejection while simultaneously enhancing graft capillary density.

Structured PICO

Does AAV2.9-mediated gene transfer of thymosin ß4 improve graft survival and attenuate rejection in a pig model of heterotopic heart transplantation?

Population

Landrace or Munich mini pigs undergoing heterotopic, abdominal transplantation of cardiac allografts (n=5 per group)

Intervention

AAV2.9.Tß4 and vascular endothelial growth factor added to autologous blood for in situ perfusion of the donor organ for 45 min before transplantation, followed by 10 days of immunosuppression

Comparator

AAV2.9.LacZ and vascular endothelial growth factor added to autologous blood for in situ perfusion of the donor organ for 45 min before transplantation, followed by 10 days of immunosuppression

Outcome

Graft survival, transgene expression, capillary density, graft function, and rejectionsurrogate

In situ AAV2.9-mediated gene transfer of thymosin β4 prolonged graft survival and attenuated rejection in a preclinical pig model of heart transplantation.

Cite This Study

Postrach et al. (2014) studied this question.

synapsesocial.com/papers/6a8a92ca5c716ca1a5d47afc https://doi.org/10.1097/tp.0000000000000327

Topics

Heart transplantation

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Adeno-Associated Viral Vector 2.9 Thymosin ß4 Application Attenuates Rejection After Heart Transplantation

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Adeno-Associated Viral Vector 2.9 Thymosin ß4 Application Attenuates Rejection After Heart Transplantation

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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Topics

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