ABSTRACT
Organ shortage has become one of the major challenges hindering the development of organ transplantation. Xenotransplantation is one of the most valuable methods to resolve global organ shortage. In recent years, the development of genetic engineering technique and research and development of new immunosuppressant have provided novel theoretical basis for xenotransplantation. International scholars have successively carried out researches on xenotransplantation in genetically modified pigs to non-human primates or brain death recipients, making certain substantial progresses. However, most of the researches are still in the preclinical stage, far from clinical application. Therefore, according to the latest preclinical experimental research progress at home and abroad, the history of xenotransplantation, the development of gene modification technology, xenotransplantation rejection and immunosuppression regimens were reviewed, aiming to provide reference for subsequent research of xenotransplantation, promote clinical application of xenotransplantation and bring benefits to more patients with end-stage diseases.
ABSTRACT
Objective To evaluate the clinical efficacy of adult kidney transplantation from unilateral pediatric donor kidney. Methods Clinical data of pediatric donors (n=10) and adult recipients (n=19) undergoing kidney transplantation were retrospectively analyzed. The changes of renal function, liver function and the maximal diameters of the kidney allografts were compared at 1, 7, 14, 28, 60 d after operation. The short-term survival and incidence of postoperative complications of the recipients were analyzed. Results Ten donors included 6 males and 4 females, aged (7±3) years old, with a body mass index (BMI) of (16.3±3.8) kg/m2. All donors were donation after brain death followed by cardiac death. Among 19 recipients, 12 were males and 7 were females, aged (34±12) years old, with a BMI of (20.3±1.3) kg/m2.An oblique incision was created in the lower right abdomen of the recipients. The arteries and veins of donor kidney were anastomosed with the external iliac arteries and veins of the recipients. The ureter of donor kidney was anastomosed with the bladder of the recipients. After anastomosis, the kidney was placed and fixed in the right iliac fossa. The serum creatinine and blood urea nitrogen levels of the recipients were decreased at 1 week after kidney transplantation, and restored to normal range at postoperative 2 weeks. All parameters related to liver function were normal after operation. At postoperative 1 month, the maximal diameters of the kidney allografts were (9.5±0.3) cm on average, which basically reached those of normal adults. The 1-year survival rate of 19 recipients was 95%. One recipient died from pulmonary infection after ineffective treatment. Two recipients developed rejection, and 1 recipient experienced urinary system infection, who were healed after corresponding treatment. Conclusions Adult kidney transplantation from unilateral pediatric donor kidney is safe, feasible and effective, which can be utilized to enlarge the source of donor kidneys.
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Objective To investigate the role and mechanism of A20 protein in the phenotypic transformation of human dermal fibroblasts (Fb) to myofibroblasts (MFb).Methods Primary human normal skin Fb (NFb) and scar skin Fb (HFb) were isolated and cuhured by enzymatic digestion.The cells were used in logarithmic growth phase at 3-5 passages,and Fb was stimulated by transforming growth factor-β (TGF-β) to mimic the Fb to MFb transformation process.Cell transfection was conducted to knock out the expression of A20 in Fb,and quantitative real-time polymerase chain reaction (PCR) test,protein immunoblotting test were conducted to detect A20,type Ⅰ collagen (Col Ⅰ),type Ⅲ collagen (Col Ⅲ)and α-smooth muscle (α-SMA),and p-Smad 2 expression in Fb.Results Compared with normal skin Fb,A20 was down-regulated in pathological scar Fb (P ＜ 0.05).After TGF-β stimulated,A20 expression was significantly decreased (P ＜ 0.05),while the expression of fibrosis associated molecules such as Col Ⅰ,Col Ⅲ and α-SMA and p-Smad 2 was significantly increased (P ＜ 0.05) in Fb.Knockout of A20 in Fb further promoted TGF-β induced the expression of fibrosis associated molecules such as Col Ⅰ,Col Ⅲ and o-SMA and p-Smad 2 (P ＜ 0.05).Conclusions A20 protein is involved in the process of human dermal Fb to MFb phenotype transformation,and A20 negatively regulates the transformation effect mediated by TGF-β by inhibiting the activation of Smad signaling pathway.