?当蝾螈失去四肢时，它们能再生出新的肢体。而最近Max Planck研究所位于Bad Nauheim的心肺研究中心科学家们发现一种蝾螈的心脏能再生，他们目前正在研究这种再生的细胞学机制。哺乳动物包括人类都不具备这种能力，所以研究结果可能为器官受损的病人带来新的治疗手段，结果见最新的《Journal of Cell Science》。
??这种红色斑点的蝾螈Notophthalmus viridescens是科学家最喜欢的动物之一。它们来自北美的湿地，科学家在它们身上发现了有趣的现象：人类无法使受到损伤的心肌细胞再生，而且受损细胞会以结痂代替，但是这种蝾螈的心脏能完全再生，而且功能不受影响。
??其中的关键在于心肌细胞。当蝾螈的心脏经受损伤时，这些细胞会失去其本身特性，进行去分化。科学家发现心肌的特有蛋白——肌浆球蛋白和多种肌钙蛋白——在这过程中下降了。与此同时，细胞进行分化来创造新的心脏。这需要大约2周的时间。这一过程中蛋白质又恢复正常。
??科学家将这些心肌细胞分离出来并进行培养。在大部分细胞中，Braun和同事发现了Phospho-H3蛋白的存在。这种蛋白是细胞周期中G2过程的原因，并且显示了心脏再生没有干细胞的参与。而且心肌细胞再生没有遗留下愈合组织。Max Planck研究所的科学家们期望对于在蝾螈心肌再生过程的相关分子组织的更好了解能为遭受心脏疾病的人们带来治疗的新希望。
英文原文：
Newts which Regrow their Hearts
When a newt loses a limb, the limb regrows. What is more, a newt can also completely repair damage to its heart. Scientists at the Max Planck Institute for Heart and Lung Research in Bad Nauheim have now started to decode the cellular mechanisms in this impressive ability to regenerate and have discovered the remarkable plasticity of newt heart cells. As mammals, and therefore also humans, do not have this ability, the findings could contribute to new cell therapies for patients with damaged organs (Journal of Cell Science, 2006).
Fig. 1: Notophthalmus viridescens, the red-spotted newt.
Image: Max Planck Institute for Heart and Lung Research
The red-spotted newt, Notophthalmus viridescens, is a favourite animal of the researchers working with Thomas Braun in Nauheim. This amphibian comes from the wetlands of North America, but it also feels quite at home in the Institute’s aquaria. It is a small animal that scientists find interesting for a particular reason: whereas humans cannot regenerate damaged heart muscle adequately after a heart attack and the destroyed muscle tissue scars over instead, following damage, a newt’s heart can be completely repaired and the organ’s function can be completely restored.
The key to this ability to regenerate are the heart muscle cells themselves. When a newt’s heart sustains damage, its cells can lose their characteristic properties; they can dedifferentiate. The researchers were able to show that proteins typical of heart muscle cells - the heavy myosin chain and various troponins - were dramatically down-regulated in this process. At the same time, the cells embark on massive cell division to build up new heart muscle. It takes around two weeks for the heart function to be restored in the newt. The data shows that at this point the expression of the muscle-specific proteins is again normal, i.e. the cells have differentiated again, and have regained their characteristic properties.
The researchers isolated the heart muscle cells and cultured them. In most of the cells, Braun and his colleagues were able to demonstrate the existence of a protein called Phospho-H3. This protein is a marker for the G2 phase of the cell cycle and indicates that the newt heart regenerates without the involvement of stem cells. It also seems that the heart regeneration does not create typical wound healing tissue, called a blastema. Braun explains this finding: "The heart only has a relatively small number of different cell types. This could be a reason why the regeneration of heart tissue does not require a blastema." The researchers in Bad Nauheim found no indication that stem cells were involved in repairing newt hearts.
Fig. 2: Left: After two weeks, heart muscle cells injected into a regenerating leg produce proteins that are typical for skeletal muscle cells (green). The cells were previously stained red so that orange is created by overlaying the two colours. Right: As early as two days after the injection, the heart muscle marker troponin T can no longer be found in the injected cells - again stained red. The insert shows a piece of stained heart muscle as a control, which glows green due to the troponin T staining.
Image: Max Planck Institute for Heart and Lung Research
The process of regenerating lost extremities is different. Unlike in the process with the heart, newts develop a blastema in this case. Blastema cells have certain characteristics in common with stem cells, such as the development into different cell types. The cell biologists in Bad Nauheim injected isolated heart muscle cells into a newt’s leg that was regrowing after amputation. In this environment, the cells began to de-differentiate, as they did in the heart. However, this did not happen when they were injected into an undamaged extremity. Again, the researchers registered the very rapid loss of heart muscle-specific proteins.
"We suspect that the signal for the de-differentiation comes from the area where the wound is healing and the cells communicate with each other," explains Braun. These signals could be transmitted via certain enzymes, for example. An enzyme of this nature - focal adhesion kinase -, which plays a part in the transmission of signals in the cells, is phosphorylated in the transplanted cells and is thus active. The Max Planck researchers in Bad Nauheim hope that better understanding of the molecular issues involved in regeneration in the newt will open up new possibilities for the repairing human patients’ damaged hearts.
