多学科研究团队开始了牙釉质生产的第一步

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标签：#dental

西雅图华盛顿大学的研究小组利用干细胞技术形成了分泌牙釉质蛋白的类器官。

The team from the University of Washington in Seattle used stem-cell technologies to form organoids that secrete tooth enamel proteins.

在这张正在发育的门牙图像中，颜色表示在每个发育阶段表达的基因。| 图片来源：© 华盛顿大学牙科类器官研究团队

在《发育细胞》杂志上发表的一篇论文中，来自西雅图华盛顿大学的一个多学科研究小组最近宣布创造出一种类器官，可以分泌形成牙釉质所需的蛋白质。

In a paper published in the journal Developmental Cell, a multi-disciplinary team of researchers from the University of Washington in Seattle, recently announced the creation of organoids that secrete the proteins required to form tooth enamel.

“这是实现我们长期目标的关键的第一步，即开发基于干细胞的治疗方法来修复受损的牙齿并再生丢失的牙齿，”华盛顿大学牙科学院修复牙科教授、研究团队之一的张海说道。 ——作者在新闻稿中说道。

“This is a critical first step to our long-term goal to develop stem cell-based treatments to repair damaged teeth and regenerate those that are lost,” Hai Zhang, professor of restorative dentistry at the UW School of Dentistry and one of the co-authors says in a press release.

使用干细胞作为再生人体器官的基础长期以来一直是研究人员的目标，而牙齿是一个很好的起点，因为它们的结构比其他器官更简单，而且人体没有办法替代它失去的牙釉质。

Using stem cells as the basis of regrowing human organs has long been a goal of researchers, and teeth are a great place to start because they are a simpler structure than other organs, and the human body does not have a way to replace enamel it loses.

牙釉质是人体中最坚硬的物质，它是在牙齿形成过程中由称为成釉细胞的特殊细胞产生的，一旦牙齿形成完成，这些细胞就会死亡。

Enamel is the hardest substance in the human body, and it is created during the formation of teeth by specialized cells called ameloblasts that die off once tooth formation is complete.

“我们希望能够替代的许多器官，如人类胰腺、肾脏和大脑，都是巨大而复杂的。从干细胞中安全地再生它们需要时间，”研究负责人、生物化学教授、华盛顿大学干细胞和再生医学研究所副所长 Hannele Ruohola-Baker 博士说。“另一方面，牙齿要小得多，也不那么复杂。它们也许是唾手可得的果实。我们可能需要一段时间才能重新生成它们，但我们现在可以看到实现这一目标所需的步骤。”

“Many of the organs we would like to be able to replace, like human pancreas, kidney and brain, are large and complex. Regenerating them safely from stem cells will take time,” says research lead Hannele Ruohola-Baker, PhD, professor of biochemistry and associate director of the UW Medicine Institute for Stem Cell and Regenerative Medicine. “Teeth on the other hand are much smaller and less complex. They’re perhaps the low hanging fruit. It may take a while before we can regenerate them, but we can now see the steps we need to get there.”

发现这些步骤是一个漫长的过程。为了说服干细胞在实验室中生长成成釉细胞，研究人员首先研究了自然产生它们的基因编程。这是通过单细胞组合索引 RNA 测序 (sci-RNA-seq) 实现的，该测序旨在通过跟踪不同阶段的信使 RNA 水平来显示细胞发育不同阶段的活性基因。

Discovering those steps was a lengthy process. In order to convince stem cells to grow into ameloblasts in the laboratory, researchers first studied the genetic programming that produces them naturally. This was accomplished using single-cell combinatorial indexing RNA sequencing (sci-RNA-seq), which is designed to show the active genes during different stages of a cell's development by tracking the levels of messenger RNA through the different stages.

在这项研究中，sci-RNA-seq 用于创建牙齿发育每个阶段的一系列基因激活“快照”。这些数据被输入 Monocle，这是一种复杂的分析软件应用程序，可以生成将干细胞发育成成釉细胞的基因活动的可能轨迹。

In this research, sci-RNA-seq was used to create a series of "snapshots" of gene activation at each stage of tooth development. This data was fed into Monocle, a sophisticated analysis software application that produced the likely trajectory of gene activities to develop stem cells into ameloblasts.

“计算机程序可以预测你如何从这里到达那里，以及构建成釉细胞所需的路线图和蓝图，”Ruohola-
Baker 说。

“The computer program predicts how you get from here to there, the roadmap, the blueprint needed to build ameloblasts,” Ruohola-Baker says.

为了在实验室中重现这一过程，研究人员将干细胞暴露于已知可激活不同基因的化学信号中。这样做是为了模仿 sci-RNA-seq 数据预测的路径，但根据新闻稿，这一过程中仍然需要大量的试验和错误。

To then recreate the process in the lab, researchers exposed stem cells to chemical signals known to activate different genes. This was done to mimic the path predicted by the sci-RNA-seq data, but according to the press release it still required a lot of trial and error along the way.

该项目的发现之一是一种名为亚成牙本质细胞的新细胞类型，研究人员认为它是成牙本质细胞的祖细胞，而成牙本质细胞也在牙齿形成中发挥作用。

One of the discoveries during the project was a new cell type named subodontoblast which researchers believe to be a progenitor of odontoblasts which also play a role in tooth formation.

然后，由干细胞产生的细胞可以被诱导形成小型的 3D 多细胞类器官，这些类器官可以将自身组织成与发育中的牙齿相似的结构。这些类器官还分泌成釉素、釉原蛋白和牙釉质，这三种必需蛋白质形成基质并矿化形成牙釉质。

The cells created from the stem cells could then be induced to form small, 3D, multicellular organoids which organized themselves into structures similar to those seen in developing teeth. These organoids also secreted ameloblastin, amelogenin, and enamelin, 3 essential proteins that form a matrix and mineralize to form enamel.

这一系列研究的下一步是改进这些类器官的生产，并成功创造出具有与天然牙列相似的耐用性的牙釉质。最终，这一系列研究可能会导致牙釉质填充，甚至可能重新长出整个牙齿。

The next steps for this line of research are refining the production of these organoids and successfully creating enamel with durability similar to that found in natural dentition. Eventually, this line of research could lead to enamel dental fillings, and even potentially regrowing entire teeth.

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