Eskitis Institute for Cell and Molecular Therapies, National Centre for Adult Stem Cell Research, Griffith University, Nathan, Queensland, Australia.
Cell Transplant. 2011;20(11-12):1673-91. doi: 10.3727/096368911X576009. Epub 2011 Apr 29.
There is worldwide enthusiasm for the prospect of some kind of cellular transplant therapy for repair of failing organs. The olfactory mucosa of a patient's nose is easily biopsied to provide a ready source of multipotent cells. In this article we address practical issues pertinent to using olfactory neural stem cells for tissue repair. These cells are emerging as potentially most significant candidates for human tissue repair strategies. Previously we have shown that stem cells from olfactory mucosa are multipotent. As well, we have recently published three potential clinical applications. Their expression of dopaminergic markers in vitro and in a Parkinson's rat transplant model has been demonstrated. Their conversion to chondrogenic phenotype in vitro and in vivo has also been described, as has their transplant into a rat model of cardiac infarction. Here we examine in detail the biology of the olfactory neural stem cell using the rat as our animal model cell source. We establish its presence by examining self-renewal capacity and for phenotypic acquisition in inductive circumstances. We determine its frequency within the cell population and show that our culture system selects for this putative stem cell. Our studies demonstrate that adult olfactory stem cells, when transplanted into an environmental niche different from that of their origin, are able to demonstrate multipotency by acquiring the phenotype of the resident cells. We investigate how immediate the instruction need be. We test the hypothesis that olfactory neurospheres contain stem cells whose capacity for differentiation is triggered by signals of the immediate environmental niche. Significantly, of importance to any tissue regeneration endeavor, stem cell numbers were shown to be enriched by our culture methods. This was confirmed whether measured by sphere-forming capacity or differentiation response rate.
全世界都热衷于研究某种细胞移植疗法，以期修复衰竭的器官。患者鼻腔的嗅黏膜很容易被活检，从而提供多能细胞的现成来源。本文将探讨使用嗅神经干细胞进行组织修复的相关实际问题。这些细胞作为人类组织修复策略的潜在最佳候选者正逐渐受到关注。我们之前已经证明嗅黏膜中的干细胞具有多能性。此外，我们最近还发表了 3 个潜在的临床应用。已经证明它们在体外和帕金森病大鼠移植模型中表达多巴胺能标志物，并且可以在体外和体内转化为软骨细胞表型，还可以移植到大鼠心肌梗死模型中。在这里，我们使用大鼠作为动物模型细胞来源，详细研究嗅神经干细胞的生物学特性。我们通过检查自我更新能力和在诱导条件下的表型获得情况来确定其存在。我们确定了其在细胞群体中的频率，并表明我们的培养系统选择了这种假定的干细胞。我们的研究表明，成年嗅干细胞在移植到与其起源不同的环境龛位时，能够通过获得驻留细胞的表型来展示多能性。我们研究了这种指令需要多么即时。我们测试了这样一个假设，即嗅神经球包含干细胞，其分化能力是由即时环境龛位的信号触发的。重要的是，对于任何组织再生努力来说，我们的培养方法都显示出干细胞数量增加。这无论是通过球体形成能力还是分化反应速率来衡量都是如此。
