Science Education: Why do some organisms regenerate, while others don’t?

Sravanti Uppaluri and Harshitha Kanchamreddy, in the i wonder magazine, explain why it may be useful to study regeneration in nature, apart from it being an awe-inspiring process.

All of us have seen movies or heard stories of fights between gods and demons where hands or heads get severed, but grow back magically. In reality, humans do not have the ability to grow new hands or heads, but there are many organisms that do. The ability to regrow lost or damaged parts of the body is called regeneration..

Almost all regeneration occurs due to the presence of stem cells. Stem cells have the potential to become’ any other kind of cell in the body through a process called differentiation. This process allows cells to perform specific functions. 

For example, the cells in our liver (called hepatocytes) are different from the cells in our heart (called cardiomyocytes). Hepatocytes cannot function as cardiomyocytes, and vice versa. Therefore, as you can imagine, the regeneration of the liver will require stem cells capable of differentiating into hepatocytes (see Fig. 1).

  • I wonder issue 4 may 2020 diving into the world of regeneration fig 1

Fig. 1. Stem cells differentiate into various cell types. 

A fertilised egg divides to form a cluster of totipotent’ stem cells. Each cell in this cluster has the potential to form all other cell types in the human body, as well as extraembryonic or placental cells. Some cell divisions later, these totipotent stem cells differentiate into pluripotent ones. 

Pluripotent embryonic cells can form any of the cell types in the human body except the placenta. Each pluripotent embryonic cell divides and specializes to form multipotent cells. Multipotent stem cells can develop into a limited number of cell types within a particular lineage. The different multipotent cells divide and differentiate into blood cells, neurons, muscle cells, etc. Each of these can only grow into cells of their own kind.

Credits: Sravanti Uppaluri & Harshitha Kanchamreddy. License: CC-BY-NC.

Regeneration can occur at many levels, ranging from the microscopic cell to the macroscopic body. For example, we lose nearly 200,000,000 skin cells every hour, but these cells are continuously replaced by new ones.1

If a lizard on the wall loses its tail in an accident, it can regrow it. Its cousin, the axolotl, can regrow not only a new tail, but also new limbs, retina, and even parts of its brain and heart.

The common earthworm, which we see emerging from the soil after the rains, also has some regenerative capacity. It may be evident from these and other observations (see Examples I‑V) that not all organisms have the same regenerative capacity.

  • I Wonder Issue 4 May 2020 diving into the world of regeneration examples 1
  • I Wonder Issue 4 May 2020 diving into the world of regeneration examples 2
  • I Wonder Issue 4 May 2020 diving into the world of regeneration examples 3
  • I Wonder Issue 4 May 2020 diving into the world of regeneration examples 4
  • I Wonder Issue 4 May 2020 diving into the world of regeneration examples 5

Regeneration in humans

At first glance, humans don’t seem to have the regenerative capacities that amphibians and plants do. But keep in mind that regeneration can have a wide ranging definition.

On the one hand, the most common example of regeneration in humans is seen in the skin. Our skin cells are constantly being replaced, and our wounds getting healed (often without scars). On the other hand, the human liver can fully recover its form and function from as little as one fourth of its original mass. In fact, this organ has the strongest regenerative ability in our body.

Why does this organ retain this ability, and not others? We don’t have a complete answer to this question, but can take a guess by looking at the liver’s regenerative capacity from an evolutionary perspective. As a detoxifier and regulator of blood glucose, ammonia, and lipid levels in the body, the liver is essential for the functioning of the brain and other essential organs. It also processes all circulation exiting the intestines, spleen, and pancreas. 

Consequently, the liver is prone to damage from chemical toxins and diseases. Left unchecked, this damage can result in liver failure. Not surprisingly, in most vertebrates, the liver retains its regenerative capacity — a capacity that is most likely to have been selected for in the hostile environment of our evolutionary past.2

While humans cannot match the regenerative capacities of an axolotl, the genes that give the axolotl the ability to regenerate parts of its brain and heart muscle also allow the regeneration of our fingertips. Yes, you read that correctly — up to a certain age, humans can replace relatively small amputations of a fingertip. A similar ability in mice depends on stem cells found under their nails. Since we share many regeneration genes with mice, it is likely that the same mechanism may be at play in humans.3

Parting thoughts

Regeneration in different organisms has mostly been studied by removing a body part (cells, tissues, limbs, organs, etc.) and observing subsequent processes. As we develop increasingly sophisticated laboratory techniques, we are beginning to identify the genes and proteins involved in regeneration.

Apart from how awe-inspiring this process is, it may be useful to study regeneration in nature because:

  1. Humans lose limbs due to accidents, infections, or even birth defects. Understanding the regenerative process at the level of genes, cells and organs across the plant and animal kingdoms is likely to yield useful insights for medical applications.
  2. Regeneration is not very different from a dividing embryo — both
    processes involve the division of cells to form functional body parts. Since it is often difficult to study an embryo, capturing the process of regeneration offers us a window to understanding how embryos develop.
  3. Studying organisms that have adapted their regenerative capacities to their environment can show us how such diversity has come about. It can also provide insights into the evolution of these organisms.

Learning more about the different mechanisms for regeneration used in the animal world could help us replicate this process in humans too. We have already made a lot of progress in this field. For example, we have identified stem cells in multiple human tissues. By inducing these cells to grow into different cell types, we are able to produce organ and tissue replacements to damaged parts in humans. 

While many mysteries about regeneration remain, with ever-increasing knowledge, we might just be able to imagine a day when we can grow back an amputated head, like the demons from many Indian stories!

  • I Wonder Issue 4 Mainto the world of regeneration try this out fig 6

Key Takeaways

  • Regeneration is the capacity to regrow a lost body part, and recover a function.
  • Regenerative capacity varies across the plant and animal kingdom. Some organisms can regenerate cells, others can regenerate full organs.
  • Investigating regenerative capacity is possible even at the school level by studying simple invertebrates and plants.
  • Gaining an understanding of regeneration has applications in medicine and developmental biology.

References:

  1. New insights into skin cells could explain why our skin doesn’t leak (2016). ScienceDaily: https://​www​.sci​encedai​ly​.com/​r​e​l​e​a​s​e​s​/​2016​/​11​/​161129114910.htm.
  2. Michalopoulos, G. K. Liver Regeneration. J. Cell. Physiol. 213, 286 – 300 (2007).
  3. Yong, E. How nails regenerate lost fingertips. Nat. News. doi:10.1038/nature.2013.13192.e34

About the authors:

Sravanti Uppaluri teaches biology in the undergraduate programme at Azim Premji University. She is interested in developmental biology, and all life that can regenerate. She can be reached at sravanti.​uppaluri@​apu.​edu.​in

Harshitha Kanchamreddy is an alumnus of Azim Premji University, and is currently pursuing a Master’s degree at Manipal University. She loves reading and writing about science. Harshitha can be reached at sreeharshitha.kanchamreddy@​apu.​edu.​in

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