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胚胎猪胰腺移植减少免疫反应

时间:2009-05-15 10:38来源:未知 作者:Doctor001 点击:
一项灵长类研究表明,来自猪的胚胎组织在经过移植后可以在宿主体内生长成整个胰腺。Gil Hecht及其同事提出,利用胚胎胰腺而非成人胰腺可以帮助宿主发育出该器官,并让血管网渗透到其中,这可以减少针对外来组织的免疫反应的强度。 猪的器官长久以来被考虑用于
一项灵长类研究表明,来自猪的胚胎组织在经过移植后可以在宿主体内生长成整个胰腺。Gil Hecht及其同事提出,利用胚胎胰腺而非成人胰腺可以帮助宿主发育出该器官,并让血管网渗透到其中,这可以减少针对外来组织的免疫反应的强度。
猪的器官长久以来被考虑用于人类移植,但是强烈的免疫反应和抑制可能的器官排斥所需的强效复方药物是重大的障碍。这组科学家把猪胚胎胰腺移植到了每组两只共两组猴子的体内。然后让这些猴子出现人造糖尿病。第一组出现了感染并导致了早死。这组作者发现他们最初对猴子的免疫抑制必需的剂量估计过高,而且他们能在第二组显著降低剂量,后者在接受移植后生存了将近一年。关键的成就在于这些猴子在手术后的4个月中几乎不需要外来的胰岛素。这组作者说,与成人组织相比,移植的胚胎胰岛显示出了承受压力和再生的显著能力。
推荐原始出处:
PNAS May 11, 2009, doi: 10.1073/pnas.0812253106
Embryonic pig pancreatic tissue for the treatment of diabetes in a nonhuman primate model
Gil Hechta,1, Smadar Eventov-Friedmana,1, Chava Rosena, Elias Shezena, Dalit Tchorsha, Anna Aronovicha, Enrique Freudb, Hana Golana, Ronit El-Hasidc, Helena Katchmana, Bernhard J. Heringd, Amnon Zunge, Zipi Kra-Ozf, Pninit Shaked-Mishanf, Alex Yusimg, Alex Shtabskyh, Pavel Idelevitcha, Ana Tobari, Alon Harmelinj, Esther Bachar-Lustiga and Yair Reisnera,2
Xenotransplantation of pig tissues has great potential to overcome the shortage of organ donors. One approach to address the vigorous immune rejection associated with xenotransplants is the use of embryonic precursor tissue, which induces and utilizes host vasculature upon its growth and development. Recently, we showed in mice that embryonic pig pancreatic tissue from embryonic day 42 (E42) exhibits optimal properties as a β cell replacement therapy. We now demonstrate the proof of concept in 2 diabetic Cynomolgus monkeys, followed for 393 and 280 days, respectively. A marked reduction of exogenous insulin requirement was noted by the fourth month after transplantation, reaching complete independence from exogenous insulin during the fifth month after transplantation, with full physiological control of blood glucose levels. The porcine origin of insulin was documented by a radioimmunoassay specific for porcine C-peptide. Furthermore, the growing tissue was found to be predominantly vascularized with host blood vessels, thereby evading hyperacute or acute rejection, which could potentially be mediated by preexisting anti-pig antibodies. Durable graft protection was achieved, and most of the late complications could be attributed to the immunosuppressive protocol. While fine tuning of immune suppression, tissue dose, and implantation techniques are still required, our results demonstrate that porcine E-42 embryonic pancreatic tissue can normalize blood glucose levels in primates. Its long-term proliferative capacity, its revascularization by host endothelium, and its reduced immunogenicity, strongly suggest that this approach could offer an attractive replacement therapy for diabetes. (责任编辑:Doctor001)
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