Hammerman Marc R
Renal Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Transpl Immunol. 2009 Jun;21(2):93-100. doi: 10.1016/j.trim.2008.10.007. Epub 2008 Nov 6.
Lack of donor availability limits the number of human donor organs. The need for host immunosuppression complicates transplantation procedures. It is possible to 'grow' new pancreatic tissue or kidneys in situ via xenotransplantation of organ primordia from animal embryos (organogenesis of the endocrine pancreas or kidney). The developing organ attracts its blood supply from the host, enabling the transplantation of pancreas or kidney in 'cellular' form obviating humoral rejection. In the case of pancreas, selective development of endocrine tissue takes place in post-transplantation. In the case of kidney, an anatomically-correct functional organ differentiates in situ. Glucose intolerance can be corrected in formerly diabetic rats and ameliorated in rhesus macaques on the basis of porcine insulin secreted in a glucose-dependent manner by beta cells originating from transplants. Primordia engraft and function after being stored in vitro prior to implantation. If obtained within a 'window' early during embryonic pancreas development, pig pancreatic primordia engraft in non immune suppressed diabetic rats or rhesus macaques. Engraftment of pig renal primordia transplanted directly into rats requires host immune suppression. However, embryonic rat kidneys into which human mesenchymal cells are incorporated into nephronic elements can be transplanted into non-immune suppressed rat hosts. Here we review recent findings germane to xenotransplantation of pancreatic or renal primordia as a novel organ replacement strategy.
供体器官的短缺限制了人类供体器官的数量。宿主免疫抑制的需求使移植程序变得复杂。通过移植动物胚胎的器官原基(内分泌胰腺或肾脏的器官发生)在原位“培育”新的胰腺组织或肾脏是可行的。发育中的器官从宿主吸引血液供应,使得以“细胞”形式移植胰腺或肾脏从而避免体液排斥成为可能。就胰腺而言,内分泌组织在移植后会选择性发育。就肾脏而言,一个解剖结构正确的功能性器官会在原位分化。基于移植来源的β细胞以葡萄糖依赖方式分泌的猪胰岛素,以前患糖尿病的大鼠的葡萄糖不耐受情况可以得到纠正,恒河猴的情况也会有所改善。原基在植入前体外保存后能够植入并发挥功能。如果在胚胎胰腺发育早期的一个“窗口期”内获取,猪胰腺原基可植入未进行免疫抑制的糖尿病大鼠或恒河猴体内。直接移植到大鼠体内的猪肾脏原基的植入需要宿主免疫抑制。然而,将人骨髓间充质细胞整合到肾单位成分中的胚胎大鼠肾脏可以移植到未进行免疫抑制的大鼠宿主中。在此,我们综述了与胰腺或肾脏原基异种移植作为一种新型器官替代策略相关的最新研究发现。