Michael Levin Bioelectricity 101 Crash Course Lesson 15: Frog Limb Regeneration: Bioelectric “Kickstarts” for Regrowth Summary
- Adult Xenopus laevis frogs, unlike their tadpole stage, do not naturally regenerate limbs after amputation. They form a scar instead of a new limb.
- The research demonstrates that a brief (24-hour) application of a wearable bioreactor (the “BioDome”) containing a specific cocktail of drugs (MDT – Multidrug Treatment) can trigger long-term (18-month) limb regeneration in these adult frogs.
- This is a “kickstart” approach – a short intervention initiates a self-sustaining regenerative cascade. It’s not about continuous treatment or micromanaging the process.
- The BioDome creates a protected, moist environment at the amputation site, mimicking aspects of embryonic development or the rapid wound closure seen in regenerating animals.
- The MDT includes five small-molecule drugs that target different aspects of regeneration: 1,4-DPCA (anti-fibrotic, pro-angiogenic), BDNF (nerve growth), GH (tissue growth), Resolvin D5 (anti-inflammatory), and Retinoic Acid (patterning morphogen).
- The regenerated limbs show significant growth, patterning (including digit-like structures), bone regrowth and remodeling, increased vascularization (blood vessels), and reinnervation (nerve growth).
- Importantly, the regenerated limbs regain function. Frogs can use them for swimming and responding to touch.
- Early changes after treatment include delayed wound closure (which is a good thing for regeneration) and increased expression of blastema markers (like SOX2).
- Transcriptomic analysis (RNA-seq) shows that the MDT activates key developmental and regenerative pathways (Wnt, Hedgehog, Notch, TGF-β) within the first 24-72 hours.
- The short, localized treatment causes gene transcription factors involved in development, morphogenesis, immune cell response to occur, at different stages of development.
- This research is a major proof-of-principle for regenerative medicine, showing that latent regenerative potential can be “awakened” in a non-regenerating vertebrate.
Michael Levin Bioelectricity 101 Crash Course Lesson 15: Frog Limb Regeneration: Bioelectric “Kickstarts” for Regrowth
So far in this course, we’ve explored the amazing world of bioelectricity, learning how cells use electrical signals to communicate, coordinate, and even “remember” their body plan. We’ve seen how planarian worms can regenerate entire bodies thanks to their bioelectric memory. Now, it’s time to see how these principles can be applied to a more complex challenge: limb regeneration in an animal that doesn’t normally do it – the adult Xenopus laevis frog.
Remember, Xenopus tadpoles can regenerate their limbs. But as they mature into frogs, they lose this ability. If an adult frog loses a leg, it doesn’t grow back; it just forms a scar. This is similar to what happens in humans and other mammals. We can heal minor wounds, but we can’t regenerate lost limbs. This makes the adult Xenopus frog a fantastic model for studying regeneration – or rather, the lack of it – and for testing interventions that might restore this lost ability.
The key to the research we’re focusing on in this lesson is the idea of a “bioelectric kickstart.” Think of it like jump-starting a car. A car’s battery might be dead, unable to start the engine on its own. But a brief jolt of electricity from another battery (the “kickstart”) can get the engine running. Once the engine is running, it can recharge its own battery and keep going.
The “kickstart” approach in frog limb regeneration is similar. Instead of trying to constantly control every step of the regeneration process (which would be incredibly difficult), the researchers aimed to give the frog’s limb a brief “jolt” of the right kind of signals – a combination of bioelectric and biochemical cues – to awaken its dormant regenerative program. Once that program is activated, the limb can (mostly) take over and regenerate on its own, without further intervention.
The two crucial components of this “kickstart” are:
- The BioDome: This is a small, wearable bioreactor – a soft, silicone device that’s fitted over the amputation site. Think of it like a tiny, customized “incubator” for the wound. It serves several important purposes:
- Creates a Protected Environment: It shields the wound from the outside environment, preventing infection and maintaining a moist, controlled microenvironment. This is crucial because, unlike salamanders or newts that heal and close wounds rapidly in any water, the Xenopus frog closes its wounds too slowly. An unassisted wound may develop infections and scarring as a response. This also prevents desiccation (drying out), which is important for bioelectric signaling.
- Mimics Embryonic Conditions: The BioDome, in a way, creates an “artificial amnion” – a fluid-filled sac that surrounds a developing embryo. Embryos develop and regenerate in a fluid environment, and the BioDome recreates this at the wound site.
- Provides a Delivery System: The BioDome contains a silk protein hydrogel. This gel acts like a sponge, holding and slowly releasing the crucial second component: the drug cocktail.
- The Multidrug Treatment (MDT): This is a carefully chosen cocktail of five small-molecule drugs, dissolved in the silk hydrogel within the BioDome. Each drug targets a different aspect of regeneration:
- 1,4-DPCA (1,4-dihydrophenonthrolin-4-one-3carboxylic acid): This is a mouthful, but its main job is to prevent fibrosis. Fibrosis is the formation of scar tissue, which is the enemy of regeneration. 1,4-DPCA also promotes the growth of new blood vessels (angiogenesis), which are essential for bringing oxygen and nutrients to the regenerating tissues.
- BDNF (Brain-Derived Neurotrophic Factor): As the name suggests, this is a growth factor that’s important for the survival and growth of neurons (nerve cells). Regenerating a limb requires growing new nerves, and BDNF helps with that.
- GH (Growth Hormone): This is a general growth stimulator, promoting the growth of various tissues.
- Resolvin D5 (RD5): This is an anti-inflammatory molecule. Inflammation is a complex process – it’s necessary for the initial stages of wound healing, but too much inflammation can hinder regeneration. Resolvin D5 helps to “resolve” inflammation, bringing it back to a balanced state.
- Retinoic Acid (RA): This is a morphogen – a signaling molecule that plays a crucial role in patterning during development. It helps to tell cells where they are in the body and what they should become. In limb regeneration, RA helps to ensure that the new limb grows with the correct structure and proportions.
The brilliance of this approach is that it’s temporary. The BioDome, with its drug cocktail, is only applied for 24 hours. After that, it’s removed, and the frog is left to its own devices. This brief intervention is enough to “kickstart” the regenerative process, which then continues on its own for months.
And what are the results? They’re truly remarkable. The frogs treated with the BioDome and the MDT showed significant limb regeneration over an 18-month period. Their limbs grew back, not perfectly, but with far more complexity and functionality than anything seen in untreated frogs. Here’s what the researchers observed:
- Soft Tissue Growth: The regenerated limbs grew much longer than the stumps of untreated frogs. They developed flattened, paddle-like structures at the end, with distinct digit-like projections. This is a huge step up from the simple, featureless spikes that form in untreated frogs.
- Bone Regrowth: X-rays and micro-CT scans showed that new bone grew from the amputation site. This bone wasn’t just a shapeless mass; it showed signs of remodeling, with features resembling the original bone structure, including ridges and depressions for muscle attachment.
- Vascularization: New blood vessels grew into the regenerated limb, providing the necessary oxygen and nutrients.
- Innervation: New nerve fibers grew into the limb, connecting it to the nervous system.
- Functional Recovery: This is perhaps the most exciting result. The frogs used their regenerated limbs! They could swim with them, and they could respond to touch, indicating that the sensory nerves had reconnected.
How does this “kickstart” work at the cellular and molecular level? The researchers investigated this using several techniques:
- Delayed Wound Closure: Interestingly, they found that the MDT treatment actually delayed the closure of the wound. This might seem counterintuitive, but it’s actually a good thing for regeneration. Rapid wound closure and scarring, as seen in untreated frogs, prevents regeneration. The delayed closure allows time for the regenerative process to get going.
- Blastema Formation: They found increased levels of SOX2, a protein that’s a marker of stem cells and progenitor cells. These cells are found in a structure called the blastema, a mass of undifferentiated cells that forms at the wound site and gives rise to the new limb. The MDT treatment seems to promote the formation of a more robust blastema.
- Transcriptomics (RNA-seq): They analyzed the gene expression in the early tissue buds that formed after amputation. This showed that the MDT treatment activated key developmental and regenerative pathways, including:
- Wnt: A crucial signaling pathway involved in embryonic development and regeneration.
- Hedgehog: Another important signaling pathway for patterning and growth.
- Notch: Involved in cell fate determination and differentiation.
- TGF-β: A complex pathway involved in both inflammation and tissue remodeling.
The RNA-seq data showed a dynamic pattern of gene expression. In the first few hours and days after treatment, genes related to inflammation, morphogenesis, and neural signaling were upregulated. Later, the gene expression shifted towards pathways involved in cell maintenance and metabolism. This suggests that the MDT treatment triggers a cascade of events, starting with an initial inflammatory response (which is necessary, but must be controlled), followed by the activation of developmental pathways, and finally the growth and differentiation of new tissues. It showed clear difference in what happened with treated animals, vs nontreated, right after amputation occurred.
This research is a major breakthrough in regenerative medicine. It shows that it’s possible to stimulate complex limb regeneration in an animal that doesn’t normally do it, using a relatively simple, brief intervention. This “kickstart” approach, combining a controlled microenvironment (the BioDome) with a targeted cocktail of signaling molecules (the MDT), opens up exciting possibilities for future therapies, not just for limb loss, but potentially for other types of tissue regeneration and repair.
Michael Levin Bioelectricity 101 Crash Course Lesson 15: Frog Limb Regeneration: Bioelectric “Kickstarts” for Regrowth Quiz
1. Adult Xenopus laevis frogs, unlike their tadpole stage, typically:
A) Regenerate limbs perfectly.
B) Form a scar instead of regenerating a limb.
C) Regenerate limbs, but only partially.
D) Don’t lose limbs.
2. The “bioelectric kickstart” approach involves:
A) Continuous electrical stimulation of the wound site.
B) A brief, localized treatment to trigger regeneration.
C) Genetically engineering the frog to regenerate.
D) Transplanting stem cells to the wound site.
3. What is the “BioDome”?
A) A type of drug used to stimulate regeneration.
B) A wearable bioreactor that creates a controlled environment at the wound site.
C) A gene that controls limb regeneration.
D) A type of frog that can regenerate limbs.
4. What is the purpose of the silk hydrogel within the BioDome?
A) Provides oxygen directly to the cells.
B) Provides no support at all, it’s just to fill in space
C) Provides a physical barrier
D) Act as a scaffold and slow-release delivery system for drugs.
5. Which of the following is NOT a component of the Multidrug Treatment (MDT)?
A) 1,4-DPCA
B) BDNF
C) Aspirin
D) Retinoic Acid
6. What is the role of 1,4-DPCA in the MDT?
A) Promote nerve growth.
B) Prevent fibrosis (scarring) and promote blood vessel growth.
C) Stimulate overall tissue growth.
D) Reduce inflammation.
7. What is the role of Retinoic Acid in the MDT?
A) Reduce inflammation
B) Prevent fibrosis.
C) Act as a morphogen, guiding tissue patterning.
D) Promote nerve growth
8. How long is the BioDome with the MDT applied to the frog’s limb?
A) Continuously for 18 months.
B) 24 hours.
C) 1 week.
D) 1 month.
9. What were some key outcomes observed in the MDT-treated frogs?
A) Formation of featureless spikes.
B) Significant limb regrowth, patterning, and functional recovery.
C) No difference compared to untreated frogs.
D) Increased scarring.
10. What is one method the body regrew bone and patterned the structure?
A) Micro-CT
B) X-Ray
C) Looking at the animal directly
D) All of the above
11. What happened with wound closer after MDT treatment and bioreactor treatment, vs untreated group?
A) There was delayed wound closure
B) Wound closed a lot quicker
C) No wound formed at all.
D) All animals died due to an infection.
12. True or False: Delayed wound closure in the MDT-treated frogs was a negative outcome, indicating a problem with the treatment.
A) True
B) False
13. What is SOX2?
A) a gene transcription factor that promotes cell repair and growth
B) A bandage put on wounds
C) A specific type of bandage with medicines infused in it
D) Another term for bioelectric signal
14. What did RNA-seq analysis reveal about the MDT treatment?
A) It had no effect on gene expression.
B) It activated key developmental and regenerative pathways.
C) It suppressed all gene expression.
D) It only affected genes related to inflammation.
15. Which of the following signaling pathways was NOT significantly activated by the MDT treatment?
A) Wnt
B) Hedgehog
C) Insulin
D) Notch
16. True or False: the study examined gene transcriptions from the wound region at multiple time points after treatmen?
A) True
B) False
17. How did the research test how functional, or working, the regenerated limbs of frogs were after treatment?
A) Using tiny treadmills.
B) Checking neuron and muscle regernation under the microscrope, including amount of nerves.
C) Testing the sensory reponse threshold with calibrated filaments
D) B and C
18. What key finding supports the importance of brief intervention in promoting regeneration?
A) They gave constant hormone supplements throughout the 18 months, constantly and very frequently, and monitered closely the drug levels in their system.
B) The frog subjects was given drugs over and over, during the 18 months, showing the importance of maintaining drug concentration, throughout regeneration.
C) 24-hour exposure triggered regenerative cascade over a very long period of time, proving short time treatmetns matter, and are sufficient.
D) Gene editing allowed frogs to develop a limb as normal.
19. How does this research relate to the broader concept of bioelectricity?
A) The nerves are part of, and influence, broader bioelectrical fields, and drugs help this action.
B) Regeneration using signals is a core concept in bioelectrity
C) Pattern formations by cells are coordinated by the field and influenced greatly by gene transcription factors
D) All of the Above.
20. What is the ultimate significance of this research?
A) It shows that frogs can regenerate limbs.
B) It provides a proof-of-principle for a new approach to regenerative medicine in vertebrates that do not regenerate, that works on electrical properties of cells and tissues..
C) It proves that limb regeneration is impossible.
D) It demonstrates the importance of continuous drug treatment for regeneration.
Michael Levin Bioelectricity 101 Crash Course Lesson 15: Frog Limb Regeneration: Bioelectric “Kickstarts” for Regrowth Answer Sheet
1. B
2. B
3. B
4. D
5. C
6. B
7. C
8. B
9. B
10. D
11. A
12. B
13. A
14. B
15. C
16. A
17. D
18. C
19. D
20. B
迈克尔·莱文 生物电 101 速成课程 第十五课：青蛙肢体再生：生物电“启动”促进再生 摘要
- 成年非洲爪蟾青蛙，与它们的蝌蚪阶段不同，截肢后通常不能自然再生肢体。 它们会形成疤痕，而不是新的肢体。
- 研究表明，短暂（24 小时）使用可穿戴生物反应器（“BioDome”），其中包含特定的药物混合物（MDT – 多药治疗），可以触发这些成年青蛙的长期（18 个月）肢体再生。
- 这是一种“启动”方法——短暂的干预会启动一个自我维持的再生级联反应。 这不是关于持续治疗或微观管理过程。
- BioDome 在截肢部位创造了一个受保护的、湿润的环境，模拟了胚胎发育或再生动物中快速伤口闭合的某些方面。
- MDT 包括五种针对再生不同方面的小分子药物：1,4-DPCA（抗纤维化、促血管生成）、BDNF（神经生长）、GH（组织生长）、Resolvin D5（抗炎）和视黄酸（模式形成形态发生素）。
- 再生的肢体表现出显着的生长、模式形成（包括指状结构）、骨骼再生和重塑、血管化增加（血管）和神经再生（神经生长）。
- 重要的是，再生的肢体恢复了功能。 青蛙可以用它们游泳并对触摸做出反应。
- 治疗后的早期变化包括延迟伤口闭合（这对再生来说是好事）和胚基标记物（如 SOX2）表达增加。
- 转录组学分析 (RNA-seq) 表明，MDT 在最初的 24-72 小时内激活了关键的发育和再生通路（Wnt、Hedgehog、Notch、TGF-β）。
- 短暂的局部治疗会导致参与发育、形态发生、免疫细胞反应的基因转录因子在不同的发育阶段发生。
- 这项研究是再生医学的一个主要原理证明，表明在非再生脊椎动物中可以“唤醒”潜在的再生潜力。
迈克尔·莱文 生物电 101 速成课程 第十五课：青蛙肢体再生：生物电“启动”促进再生
到目前为止，在本课程中，我们已经探索了生物电的神奇世界，了解了细胞如何使用电信号进行交流、协调，甚至“记住”它们的身体蓝图。 我们已经看到涡虫如何凭借其生物电记忆再生整个身体。 现在，是时候看看这些原理如何应用于更复杂的挑战：在通常不会再生的动物——成年非洲爪蟾青蛙——中进行肢体再生。
请记住，非洲爪蟾蝌蚪可以再生它们的肢体。 但当它们成熟为青蛙时，它们就失去了这种能力。 如果成年青蛙失去了一条腿，它不会长回来； 它只是形成一个疤痕。 这与人类和其他哺乳动物的情况相似。 我们可以治愈轻微的伤口，但我们无法再生失去的肢体。 这使得成年非洲爪蟾青蛙成为研究再生的绝佳模型——或者更确切地说，是缺乏再生——以及测试可能恢复这种失去的能力的干预措施。
我们将在本课中重点关注的研究的关键是“生物电启动”的概念。 可以把它想象成启动汽车。 汽车的电池可能没电了，无法自行启动发动机。 但来自另一个电池的短暂电击（“启动”）可以让发动机运转起来。 一旦发动机运转，它就可以为自己的电池充电并继续运行。
青蛙肢体再生中的“启动”方法类似。 研究人员并没有试图不断控制再生过程的每一步（这将非常困难），而是旨在给青蛙的肢体一个正确信号类型的短暂“冲击”——生物电和生化线索的组合——以唤醒其休眠的再生程序。 一旦该程序被激活，肢体就可以（大部分）接管并自行再生，而无需进一步干预。
这种“启动”的两个关键组成部分是：
- BioDome： 这是一个小型、可穿戴的生物反应器——一种安装在截肢部位的柔软硅胶装置。 可以把它想象成一个为伤口定制的微型“培养箱”。 它有几个重要的用途：
- 创建一个受保护的环境： 它可以保护伤口免受外部环境的影响，防止感染并保持湿润、受控的微环境。这一点至关重要，因为与蝾螈或蝾螈等在任何水中都能迅速愈合并闭合伤口的动物不同，非洲爪蟾 青蛙的伤口闭合速度太慢 。未加任何辅助措施的伤口可能会发生感染和疤痕反应.这还可以防止干燥，这对于生物电信号传导很重要。
- 模拟胚胎条件： BioDome 在某种程度上创造了一个“人造羊膜”——一个充满液体的囊，包围着发育中的胚胎。 胚胎在流体环境中发育和再生，而 BioDome 在伤口部位再现了这一点。
- 提供给药系统： BioDome 包含丝蛋白水凝胶。 这种凝胶就像海绵一样，可以容纳并缓慢释放第二个关键成分：药物混合物。
- 多药治疗 (MDT)： 这是精心挑选的五种小分子药物的混合物，溶解在 BioDome 内的丝蛋白水凝胶中。 每种药物都针对再生的不同方面：
- 1,4-DPCA (1,4-二氢吩并噻唑啉-4-酮-3羧酸)： 这很拗口，但它的主要工作是防止纤维化。 纤维化是疤痕组织的形成，这是再生的敌人。 1,4-DPCA 还可以促进新血管的生长（血管生成），这对于将氧气和营养物质输送到再生组织至关重要。
- BDNF（脑源性神经营养因子）： 顾名思义，这是一种对神经元（神经细胞）的存活和生长很重要的生长因子。 再生肢体需要生长新的神经，而 BDNF 对此有所帮助。
- GH（生长激素）： 这是一种一般的生长刺激剂，可促进各种组织的生长。
- Resolvin D5 (RD5)： 这是一种抗炎分子。 炎症是一个复杂的过程——它对于伤口愈合的初始阶段是必要的，但过多的炎症会阻碍再生。 Resolvin D5 有助于“消退”炎症，使其恢复到平衡状态。
- 视黄酸 (RA)： 这是一种形态发生素——一种在发育过程中模式形成中起关键作用的信号分子。 它可以帮助告诉细胞它们在体内的位置以及它们应该变成什么。 在肢体再生中，RA 有助于确保新的肢体以正确的结构和比例生长。
这种方法的妙处在于它是暂时的。 带有药物混合物的 BioDome 仅应用24 小时。 之后，它会被移除，青蛙就可以自行其是。 这种短暂的干预足以“启动”再生过程，然后该过程会自行持续数月。
结果如何？ 它们确实非常了不起。 用 BioDome 和 MDT 治疗的青蛙在 18 个月的时间里表现出显着的肢体再生。 它们的肢体长回来了，虽然不完美，但比未治疗的青蛙看到的任何东西都复杂得多，功能也强得多。 以下是研究人员观察到的情况：
- 软组织生长： 再生的肢体比未治疗青蛙的残端长得多。 它们在末端形成了扁平的、桨状的结构，具有明显的指状突起。 这比未治疗青蛙中形成的简单、无特征的尖刺有了很大的进步。
- 骨骼再生： X 射线和 micro-CT 扫描显示，新骨骼从截肢部位长出。 这种骨骼不仅仅是一个无定形的肿块； 它显示出重塑的迹象，其特征类似于原始骨骼结构，包括用于肌肉附着的脊和凹陷。
- 血管化： 新的血管长入再生的肢体，提供必要的氧气和营养。
- 神经支配：新的神经纤维长入肢体，将其与神经系统连接起来。
- 功能恢复：这也许是最令人兴奋的结果。青蛙能够 *使用* 它们再生的四肢了!它们可以用其来游泳，且它们会对触碰有反应, 说明感觉神经是重新连接了的.
这种“启动”在细胞和分子水平上是如何工作的？ 研究人员使用多种技术对此进行了调查：
- 延迟伤口闭合： 有趣的是，他们发现 MDT 治疗实际上延迟了伤口的闭合。 这似乎违反直觉，但实际上对再生来说是好事。 未治疗青蛙中看到的快速伤口闭合和疤痕形成阻止了再生。 延迟闭合为再生过程的启动提供了时间。
- 胚基形成： 他们发现SOX2水平升高，SOX2 是一种干细胞和祖细胞的标志蛋白。 这些细胞存在于一种叫做胚基的结构中，胚基是在伤口部位形成的一团未分化细胞，可以产生新的肢体。 MDT 治疗似乎促进了更强健的胚基的形成。
- 转录组学 (RNA-seq)： 他们分析了截肢后形成的早期组织芽中的基因表达。 这表明 MDT 治疗激活了关键的发育和再生通路，包括：
- Wnt： 参与胚胎发育和再生的关键信号通路。
- Hedgehog： 另一个重要的模式形成和生长信号通路。
- Notch： 参与细胞命运决定和分化。
- TGF-β： 一种复杂的通路，参与炎症和组织重塑。
RNA-seq 数据显示了基因表达的动态模式。 在治疗后的最初几个小时和几天里，与炎症、形态发生和神经信号传导相关的基因被上调。 之后，基因表达转向参与细胞维持和代谢的途径。 这表明 MDT 治疗会触发一系列事件，首先是最初的炎症反应（这是必要的，但必须加以控制），然后是发育通路的激活，最后是新组织的生长和分化。 它显示了接受治疗的动物与未接受治疗的动物在截肢后发生的情况的明显差异。
这项研究是再生医学的一项重大突破。 它表明，使用相对简单、短暂的干预措施，可以刺激通常不会再生的动物的复杂肢体再生。 这种“启动”方法将受控的微环境 (BioDome) 与靶向信号分子混合物 (MDT) 相结合，为未来的治疗开辟了令人兴奋的可能性，不仅适用于肢体缺失，还可能适用于其他类型的组织再生和修复。
迈克尔·莱文 生物电 101 速成课程 第十五课：青蛙肢体再生：生物电“启动”促进再生 小测验
1. 成年非洲爪蟾青蛙，与它们的蝌蚪阶段不同，通常：
A) 完美再生肢体。
B) 形成疤痕而不是再生肢体。
C) 再生肢体，但只是部分再生。
D) 不会失去肢体。
2. “生物电启动”方法涉及：
A) 持续电刺激伤口部位。
B) 短暂的局部治疗以触发再生。
C) 对青蛙进行基因工程以使其再生。
D) 将干细胞移植到伤口部位。
3. 什么是“BioDome”？
A) 一种用于刺激再生的药物。
B) 一种可穿戴生物反应器，可在伤口部位创造受控环境。
C) 一种控制肢体再生的基因。
D) 一种可以再生肢体的青蛙。
4. BioDome 内的丝蛋白水凝胶的用途是什么？
A) 直接向细胞供氧。
B) 不提供任何支持，只是为了填补空间
C) 提供物理屏障
D) 充当支架和药物缓释系统。
5. 以下哪一项不是多药治疗 (MDT) 的组成部分？
A) 1,4-DPCA
B) BDNF
C) 阿司匹林
D) 视黄酸
6. 1,4-DPCA 在 MDT 中的作用是什么？
A) 促进神经生长。
B) 防止纤维化（疤痕形成）并促进血管生长。
C) 刺激整体组织生长。
D) 减少炎症。
7. 视黄酸在 MDT 中的作用是什么？
A) 减少炎症
B) 防止纤维化。
C) 充当形态发生素，引导组织模式形成。
D) 促进神经生长
8. BioDome 与 MDT 一起应用于青蛙肢体多长时间？
A) 连续 18 个月。
B) 24 小时。
C) 1 周。
D) 1 个月。
9. 在 MDT 治疗的青蛙中观察到的一些关键结果是什么？
A) 形成无特征的尖刺。
B) 显着的肢体再生、模式形成和功能恢复。
C) 与未治疗的青蛙没有区别。
D) 疤痕增加。
10. 身体再生骨骼和模式化结构的其中一个方法是什么?
A) Micro-CT
B) X-Ray
C) 直接观察动物
D) 以上都是
11. MDT 治疗和生物反应器治疗后，与未治疗组相比，伤口闭合情况如何？
A) 伤口闭合延迟
B) 伤口闭合快很多
C) 根本没有形成伤口。
D) 所有动物都死于感染。
12. 对或错：MDT 治疗的青蛙伤口闭合延迟是一个负面结果，表明治疗存在问题。
A) 对
B) 错
13. 什么是 SOX2？
A) 一种促进细胞修复和生长的基因转录因子
B) 敷在伤口上的绷带
C) 一种注入药物的特殊绷带
D) 生物电信号的另一个术语
14. RNA-seq 分析揭示了关于 MDT 治疗的什么信息？
A) 它对基因表达没有影响。
B) 它激活了关键的发育和再生通路。
C) 它抑制了所有基因表达。
D) 它只影响与炎症相关的基因。
15. 以下哪种信号通路没有被 MDT 治疗显着激活？
A) Wnt
B) Hedgehog
C) 胰岛素
D) Notch
16.对或错： 该研究检查了治疗后多个时间点伤口区域的基因转录？
A) 正确
B) 错误
17. 研究如何测试治疗后青蛙再生四肢的功能性或工作情况？
A) 使用微型跑步机。
B) 检查显微镜下的神经元和肌肉再生，包括神经数量.
C) 使用校准的细丝测试感觉反应阈值
D) B 和 C
18. 哪个关键发现支持了短暂干预在促进再生中的重要性？
A) 他们在整个 18 个月内不断、非常频繁地给予激素补充剂，并密切监测他们体内的药物水平.
B) 在 18 个月内反复给青蛙受试者用药，表明在整个再生过程中保持药物浓度的重要性.
C) 24 小时的暴露在很长一段时间内触发了再生级联反应，证明短时间治疗很重要，并且是足够的.
D) 基因编辑允许青蛙正常发育肢体。
19. 这项研究如何与更广泛的生物电概念相关联？
A) 神经是更广泛的生物电场的一部分，并影响更广泛的生物电场，药物有助于这一作用。
B) 使用信号再生是生物电的核心概念
C) 细胞的模式形成由场协调，并受基因转录因子的极大影响
D) 以上都是。
20. 这项研究的最终意义是什么？
A) 它表明青蛙可以再生肢体。
B) 它为不 再生, 的脊椎动物的再生医学新方法提供了一个原理证明，该方法适用于细胞和组织的电特性。
C) 它证明肢体再生是不可能的。
D) 它证明了持续药物治疗对再生的重要性。
迈克尔·莱文 生物电 101 速成课程 第十五课：青蛙肢体再生：生物电“启动”促进再生 答案表
1. B
2. B
3. B
4. D
5. C
6. B
7. C
8. B
9. B
10. D
11. A
12. B
13. A
14. B
15. C
16. A
17. D
18. C
19. D
20. B