一項靈長類研究表明,來自豬的胚胎組織在經過移植后可以在宿主體內生長成整個胰腺。Gil Hecht及其同事提出,利用胚胎胰腺而非成人胰腺可以幫助宿主發育出該器官,并讓血管網滲透到其中,這可以減少針對外來組織的免疫反應的強度。 豬的器官長久以來被考慮用于人類移植,但是強烈的免疫反應和抑制可能的器官排斥所需的強效復方藥物是重大的障礙。這組科學家把豬胚胎胰腺移植到了每組兩只共兩組猴子的體內。然后讓這些猴子出現人造糖尿病。第一組出現了感染并導致了早死。這組作者發現他們最初對猴子的免疫抑制必需的劑量估計過高,而且他們能在第二組顯著降低劑量,后者在接受移植后生存了將近一年。關鍵的成就在于這些猴子在手術后的4個月中幾乎不需要外來的胰島素。這組作者說,與成人組織相比,移植的胚胎胰島顯示出了承受壓力和再生的顯著能力。 推薦原始出處: 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. (責任編輯:Doctor001) |