Targeted galectin-7 inhibition with ultrasound microbubble targeted gene therapy as a sole therapy to prevent acute rejection following heart transplantation in a Rodent model.
Biomaterials
; 263: 120366, 2020 12.
Article
de En
| MEDLINE
| ID: mdl-32950914
ABSTRACT
BACKGROUND:
Despite significant advances in transplantation, acute cellular rejection (AR) remains a major obstacle that is most prevalent in the first months post heart transplantation (HT). Current treatments require high doses of immunosuppressive drugs followed by maintenance therapies that have systemic side effects including early infection. In this study, we attempted to prevent AR with a myocardial-targeted galectin-7-siRNA delivery method using cationic microbubbles (CMBs) combined with ultrasound targeted microbubble destruction (UTMD) to create local immunosuppression in a rat abdominal heterotopic heart transplantation acute rejection model. METHODS ANDRESULTS:
Galectin-7-siRNA (siGal-7) bound to CMBs were synthesized and effective ultrasound-targeted delivery of siGal-7 into target cells confirmed in vitro. Based on these observations, three transplant rat models were testedï¼â isograft (ISO); â¡ Allograft (ALLO) +UTMD; and â¢ALLO + PBS. UTMD treatments were administered at 1, 3, 5, 7 days after HT. Galectin 7 expression was reduced by 50% compared to ALLO + PBS (p < 0.005), and this was associated with significant reductions in both galectin 7 and Interleukin-2 protein levels (p < 0.001). The ALLO + UTMD group had Grade II or less inflammatory infiltration and myocyte damage in 11/12 rats using International Society For Heart and Lung Transplantation grading, compared to 0/12 rats with this grading in the ALLO + PBS group at 10 days post HT (p < 0.001).CONCLUSIONS:
Ultrasound-targeted galectin-7-siRNA knockdown with UTMD can prevent acute cellular rejection in the early period after allograft heart transplantation without the need for systemic immunosuppression. KEY WORDS Microbubble, Acute Rejection, Heart Transplantation, Galectin-7, RNA.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Préparations pharmaceutiques
/
Transplantation cardiaque
Limites:
Animals
Langue:
En
Journal:
Biomaterials
Année:
2020
Type de document:
Article
Pays d'affiliation:
Chine