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

间充质干细胞（MSC）是非特化细胞，生活在骨髓中称为“利基”的局部区域。MSC是重要的，因为它们可以改变（分化）成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分化的方式和时间的方法，所以我们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，用于诸如骨质疏松症的病症）。一种众所周知的方法是用特殊的化学添加剂培养和生长MSC，使其成为某种细胞类型。但这并不理想，因为你正在使用额外的化学品。我们已经建立了一种培养MSC并控制其行为的方法，只需将它们以特定的模式印在材料上，而无需化学物质。这意味着我们可以培养MSC，并保持它们的自我更新（作为干细胞）或使它们变成成骨细胞以形成骨骼。MSC生态位内有某些信号控制MSC的命运。最近的研究表明，RNA的小片段，称为microRNA（miRNA），在这种控制中很重要。在这个项目的第一部分，我们希望使用我们的模式来控制MSC的行为，然后看看哪些miRNAs参与了控制。一旦我们确定了这些miRNAs，我们将看看我们是否可以做相反的事情，即。通过阻断（或沉默）特定的miRNA来控制MSC的行为。我们将通过设计miRNAs的阻断剂（称为miRNAs阻断剂）来实现这一点，我们将将其递送到MSC中。它们可能很难运送，所以我们将通过将Ammomir附着在小纳米颗粒上来引导它们进入细胞，这将作为出租车将Ammomir运送到MSC中。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。然而，必须注意的是，MSC龛位于骨髓中，这是一种3D组织。因此，我们项目的最后一部分将看看我们是否也可以将这些细胞出租到3D生长的MSC中，并类似地控制其中细胞的命运。这将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.