圖片來源:medicalxpress.com
刊登在國際雜誌Nature上的一篇研究報告中,來自澳大利亞和荷蘭的科學家們通過研究表示,他們在實驗室中成功利用幹細胞培養出了具有初步生長狀態的人類腎髒組織,而這一過程通向在實驗室中開發全功能性的移植器官又進了一步。
研究者表示,這種組織並不是一種有活力的組織,但可以用於其它用途,比如在藥物毒性試驗中用來替代動物模型。研究者在文章中利用誘導多能幹細胞(iPS)製造出了腎髒樣的結構。目前由於嚴重缺少捐獻的器官來移植事故或疾病受損的患者器官,因此長期以來利用幹細胞來製造人類器官一直是科學界的一大研究障礙。
科學家們需要誘導幹細胞使其分化組裝成為腎髒、肝髒和肺部細胞,隨後這些細胞就會形成具有複雜解剖學結構的真實器官進而在受體患者中發揮作用。而在這項最新研究中,研究人員就設法將誘導多能幹細胞轉化成了兩種不同類型的成體細胞。研究者Davies說道,這種培養產物並不是腎髒,而隻是一種類器官,當然作為臨床使用的有用的移植器官還需要很漫長的一段路。
研究者指出,這種類器官或許可以幫助完成一種不同的醫學需求,即檢測新藥在人類機體中的安全性,而對藥物損傷易受影響的細胞類型已經在類器官中存在了;幹細胞是一種原始細胞,隨著其生長分化形成多種特殊類型的細胞,其就會組成不同的器官,比如大腦、心髒、腎髒等。
直到幾年前,當誘導多能幹細胞被開發創造時,唯一獲得幹細胞的方法就是從人類胚胎中獲取,而目前破壞人類胚胎獲取幹細胞在科學界是具有爭議的。目前,其他的研究團隊也相繼報道在實驗室中利用多能幹細胞培養出了“類器官”胃、肝髒、視網膜、大腦以及心髒組織。
doi:10.1038/nature15695
PMC:
PMID:
Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis
Minoru Takasato, Pei X. Er, Han S. Chiu, Barbara Maier, Gregory J. Baillie, Charles Ferguson, Robert G. Parton, Ernst J. Wolvetang, Matthias S. Roost, Susana M. Chuva de Sousa Lopes &Melissa H. Little
The human kidney contains up to 2 million epithelial nephrons responsible for blood filtration. Regenerating the kidney requires the induction of the more than 20 distinct cell types required for excretion and the regulation of pH, and electrolyte and fluid balance. We have previously described the simultaneous induction of progenitors for both collecting duct and nephrons via the directed differentiation of human pluripotent stem cells1. Paradoxically, although both are of intermediate mesoderm in origin, collecting duct and nephrons have distinct temporospatial origins. Here we identify the developmental mechanism regulating the preferential induction of collecting duct versus kidney mesenchyme progenitors. Using this knowledge, we have generated kidney organoids that contain nephrons associated with a collecting duct network surrounded by renal interstitium and endothelial cells. Within these organoids, individual nephrons segment into distal and proximal tubules, early loops of Henle, and glomeruli containing podocytes elaborating foot processes and undergoing vascularization. When transcription profiles of kidney organoids were compared to human fetal tissues, they showed highest congruence with first trimester human kidney. Furthermore, the proximal tubules endocytose dextran and differentially apoptose in response to cisplatin, a nephrotoxicant. Such kidney organoids represent powerful models of the human organ for future applications, including nephrotoxicity screening, disease modelling and as a source of cells for therapy.