创新背景

虽然研究人员从2006年就已经了解了诱导多能干细胞，但科学家们仍有很多东西要了解，如何在实验室中人工和安全地模仿人体细胞分化，以提供针对性的医疗治疗。

 

创新过程

新南威尔士大学研究人员在这一领域的两项研究不仅揭示了前体血液干细胞如何在动物和人类中发生，而且揭示了它们如何被人工诱导。

在发表在《细胞报告》上的一项研究中，新南威尔士大学生物医学工程学院的研究人员演示了如何在实验室中使用微流体设备模拟胚胎心脏的跳动，从而开发出人类血液干细胞“前体”，这是一种即将成为血液干细胞的干细胞。

 

 

在发表在《自然细胞生物学》上的一篇文章中，新南威尔士大学医学与健康学院的研究人员揭示了老鼠胚胎中负责产生血液干细胞的细胞的身份。

这两项研究都是了解血液干细胞如何、何时、何地以及哪些细胞参与创造的重要步骤。

模拟心脏

在《细胞报告》中详细介绍的这项研究中，第一作者李晶晶博士和其他研究人员描述了一个3cm x 3cm的微流体系统是如何泵入从胚胎干细胞系产生的血液干细胞，以模拟胚胎的心脏跳动和血液循环状况。

她表示，在过去的几十年里，生物医学工程师一直试图在实验室培养皿中制造血液干细胞，以解决供体血液干细胞短缺的问题。但至今还没有人能够做到这一点。部分问题在于，研究人员仍然没有完全理解胚胎发育过程中微环境中发生的所有过程，这些过程导致了大约在第32天产生血液干细胞。所以他们制作了一个模拟心脏跳动和血液循环的设备，以及一个眼眶震动系统，当血细胞在设备中或在培养皿中移动时，该系统会对血细胞产生剪切应力或摩擦。

 

 

这些系统促进了前体血干细胞的发育，可分化为各种血液成分——白细胞、红细胞、血小板等。他们很兴奋地看到这个被称为造血的过程在设备中被复制了出来。

该研究的合著者罗伯特·诺顿副教授表示，他感到惊讶的是，该设备不仅创造了血液干细胞前体，进而产生了分化的血细胞，而且还创造了胚胎心脏环境的组织细胞，这对这一过程至关重要。

血液干细胞，当它们在胚胎中形成时，在称为主动脉的主血管壁中形成。它们基本上从主动脉中弹出进入循环， 然后进入肝脏，形成所谓的确定性造血，或确定的血液形成。形成主动脉，然后从主动脉实际进入循环的细胞，这是产生这些细胞所需的关键步骤。

研究人员已经证明，我们可以产生一种可以形成所有不同类型血细胞的细胞。他们还表明，它与主动脉内膜的细胞密切相关——因此他们知道它的起源是正确的——而且它会增殖。

研究人员对他们在用机械装置模拟胚胎心脏状况方面取得的成就持谨慎乐观态度。他们希望这能成为解决当今限制再生医学治疗的挑战的一步：供体造血干细胞短缺、供体组织细胞排斥，以及围绕使用体外受精胚胎的伦理问题。

 

创新关键点

新南威尔士大学悉尼分校的生物医学工程师和医学研究人员已经独立地发现了胚胎血液干细胞的创造，有一天可能会消除对干细胞献血者的需求。

研究人员制作了一个模拟心脏跳动和血液循环的设备，以及一个眼眶震动系统，当血细胞在设备中或在培养皿中移动时，该系统会对血细胞产生剪切应力或摩擦。

这些系统促进了前体血干细胞的发育，可分化为各种血液成分——白细胞、红细胞、血小板等。

 

创新价值

这些研究是再生医学朝着使用“诱导多能干细胞”来治疗疾病的方向发展的一部分，这种干细胞是从成人组织细胞中逆向工程而不是使用活的人类或动物胚胎。

在未来，这一知识可以用于帮助癌症患者，以及其他接受了高剂量放射和化疗的患者，以补充他们耗尽的血液干细胞。

 

Stem cells can be derived from adult cells rather than human embryos

Two studies in this area by UNSW researchers have revealed not only how precursor blood stem cells occur in animals and humans, but also how they can be artificially induced.

In a study published in Cell Reports, researchers at the University of New South Wales School of Biomedical Engineering demonstrated how a microfluidic device can be used in the laboratory to mimic the beating of an embryonic heart to develop human blood stem cell "precursors," a type of stem cell that is on its way to becoming a blood stem cell.

In an article published in Nature Cell Biology, researchers at the University of New South Wales School of Medicine and Health reveal the identity of the cells responsible for generating blood stem cells in mouse embryos.

Both studies are important steps toward understanding how, when, where, and which cells are involved in the creation of blood stem cells.

Simulation of the heart

In the study detailed in Cell Reports, lead author Dr Jingjing Li and other researchers describe how a 3cm x 3cm microfluidic system is pumped with blood stem cells generated from an embryonic stem cell line to mimic the heart beating and blood circulation conditions of an embryo.

For the past few decades, biomedical engineers have been trying to create blood stem cells in lab dishes to address the shortage of donor blood stem cells, she said. But no one has been able to do so yet. Part of the problem is that researchers still don't fully understand all the processes that take place in the microenvironment during embryonic development that lead to the generation of blood stem cells around day 32. So they built a device that mimics heart beating and blood circulation, as well as an orbital vibration system that creates shear stress or friction on blood cells as they move in the device or in a petri dish.

These systems promote the development of precursor blood stem cells, which can differentiate into various blood components -- white blood cells, red blood cells, platelets, etc. They were excited to see this process, called hematopoiesis, replicated in the device.

Associate Professor Robert NORTON, co-author of the study, said he was surprised that the device not only created blood stem cell precursors, which in turn gave rise to differentiated blood cells, but also tissue cells of the embryonic heart environment, which are crucial for this process.

Blood stem cells, when they form in the embryo, form in the wall of a major blood vessel called the aorta. They basically pop out of the aorta into the circulation and then into the liver to form what's called deterministic hematopoiesis, or deterministic blood formation. The formation of the aorta and then the actual entry of cells from the aorta into the circulation is a critical step required to produce these cells.
Researchers have shown that we can produce one type of cell that can form all the different types of blood cells. They also showed that it was closely associated with cells in the inner lining of the aorta - so they knew its origin was correct - and that it proliferated.

The researchers are cautiously optimistic about their success in simulating the embryonic heart condition with a mechanical device. They hope it will be a step toward addressing the challenges that limit regenerative medicine treatments today: donor hematopoietic stem cell shortages, donor tissue cell rejection, and ethical issues surrounding the use of IVF embryos.