Nanoparticles and Nanotopography: A Nano-toolbox to Control Stem Cell Self-Renewal via miRNAs

间充质干细胞(MSCs)是一种非专门化细胞，生活在骨髓中一个被称为“小窝”的局部区域。MSCs很重要，因为它们可以转变(分化)为各种不同的细胞类型，包括成骨细胞(骨细胞)、软骨细胞(软骨细胞)和脂肪细胞(脂肪细胞)，这取决于身体何时需要这些细胞。几年来，研究人员一直在试图确定控制MSCs如何以及何时分化的方法，这样我们就可以保持它们的原样(即。作为干细胞，用于移植研究等)或使它们成为某种组织(例如。骨骼，如骨质疏松)。一种广为人知的方法是用特殊的化学添加剂培养和生长MSCs，使其成为特定的细胞类型。然而，这并不理想，因为您正在使用额外的化学物质。我们已经建立了一种培养MSCs并控制其行为的方法，只需将它们种植在印记在材料上的特定图案上，而不使用任何化学物质。这意味着我们可以培养骨髓间充质干细胞，让它们自我更新(作为干细胞)，或者让它们变成成骨细胞形成骨。在MSC的利基市场中，有一些特定的信号控制着MSC的命运。最近的研究表明，被称为microRNA(MiRNA)的小片段RNA在这种控制中是重要的。在本项目的第一部分中，我们希望使用我们的模式来控制MSC行为，然后查看哪些miRNAs参与了该控制。一旦我们确定了这些miRNA，我们就会看看是否可以反其道而行之，即。通过阻止(或沉默)特定的miRNAs来控制MSC行为。我们将通过设计miRNAs的阻断剂(称为antagomir)来实现这一点，我们将把这些阻断剂输送到MSCs中。它们可能很难输送，所以我们将通过将无性体附着在小纳米颗粒上来引导它们进入细胞，纳米颗粒将作为出租车将无性体运送到骨髓间充质干细胞。这将为我们提供一种纳米颗粒工具，最终可以用于临床诱导骨形成。但必须注意的是，MSC的壁龛位于骨髓，这是一个三维组织。因此，我们项目的最后部分将看看我们是否也可以将无性恋者滑行到3D生长的MSCs中，并同样地控制其中细胞的命运。这将让我们更好地了解我们的技术是否能在体内发挥作用。

Mesenchymal stem cells (MSCs) are unspecialised cells that live in a localised area in the bone marrow called the 'niche'. MSCs are important as they can change (differentiate) into a variety of different cell types, including osteoblasts (bone cells), chondrocytes (cartilage cells) and adipocytes (fat cells), depending on when the body needs these cells. For several years now, researchers have been trying to identify methods of controlling how and when MSCs differentiate, so we can either keep them as they are (ie. as stem cells, for transplant studies etc) or make them become a certain tissue (eg. bone, for conditions such as osteoporosis). One well-known method available is to culture and grow the MSCs with special chemical additives that make them become a certain cell type. However this is not ideal, as you are using extra chemicals. We have established a way of growing MSCs and controlling their behaviour, simply by growing them on a particular pattern imprinted onto a material, with no chemicals. This means we can grow cultures of MSCs and either keep them self-renewing (as stem cells) or make them turn into osteoblasts to form bone. There are certain signals inside the MSC niche that control the MSC's fate. Recent studies have indicated that small sections of RNA, called microRNA (miRNA), are important in this control. In the first part of this project, we want to use our patterns to control MSC behaviour, and then look to see which miRNAs as involved in that control. Once we have identified these miRNAs, we will then see if we can do the reverse, ie. control MSC behaviour by blocking (or silencing) the particular miRNAs. We will do this by designing blockers of the miRNAs (called antagomirs), which we will deliver into the MSCs. They can be difficult to deliver, so we will guide them into cells by attaching the antagomirs onto small nanoparticles, which will function as taxis to ferry antagomirs into the MSCs. This will give us a nanoparticle tool, which can be ultimately used in clinic to induce bone formation.However, it must be noted that the MSC niche is located the bone marrow, which is a 3D tissue. Therefore, the final part of our project will look to see if we can also taxi the antagomirs into MSCs grown in 3D, and similarly control the fate of the cells therein. This will give a better idea of whether our technology would work in vivo.