February 24, 2020 | David F. Coppedge

How Tissues Could Last Forever

A tale from the crypt with a happy ending: eternal life.

Stem cells have been a focus of biologists and medical researchers for many years now. These cells live in many organs of the body, and have the amazing ability to differentiate into any tissue when needed. Indeed, complete differentiation occurs when a body develops from a single-celled embryo. Up to a certain stage of development, it is possible to harvest embryonic stem cells and experiment with them, or perhaps insert them into the body to regenerate damaged tissues or organs. Because this involves killing a human embryo, which many believe is a unique human being, the process is fraught with ethical qualms. Adult stem cells, which can be gathered from the body after differentiation, bypass these ethical issues.

When Nobel prize-winner Shinya Yamanaka succeeded in coaxing regular cells from skin back into a stem-like state, the medical world became very excited. His ‘induced pluripotent stem cells’ (iPSC) opened the prospect for tissue regeneration without the ethical drawbacks of embryonic stem cells. In essence, Yamanaka took differentiated cells and “de-differentiated” them back into stem cells. His initial work has become refined and made more efficient in the years since. But can the body do this? Can it de-differentiate regular cells into stem cells?

Gut Reaction

The answer is yes! A press release from the Dana-Farber Cancer Institute in Boston, Massachusetts has found that intestinal cells can de-differentiate back into stem cells, marking the first known case of “reverse development” in the body. It’s been known that intestines can repair themselves, but how?

Deep within the lining of the human intestine lies the source of the organ’s ability to renew itself and recover from damage: intestinal stem cells (ISCs), lodged in pockets of tissue called crypts, generate the cells that continuously repopulate the intestinal lining. Even the stem cells themselves have a safety net: when they’re damaged, healthy replacements appear in less than a week.

There were two theories, the article says, about how the stem cells return after loss. One theory was that they come from a reserve supply somewhere. The other was that daughter cells, after differentiation, can de-differentiate back into the stem cell state. New experiments by Ramesh Shivdasani at Dana-Farber have demonstrated that the second theory is correct. There’s no need for a secret pool of stem cells; the intestine can regenerate them at will by de-differentiating tissue cells. In principle, the intestine has ‘eternal life’ – it would be like the fuel lines in a car being able to return to the initial metal and then mold themselves over punctures. They would never need external maintenance.

Amazing FactsThe intestine is one of just three tissues in the body, along with the skin and blood, in which cells are constantly turning over – dying and being replaced by freshly made cells. They share this quality because they are the tissues most intimately in contact with material from the environment, and therefore with potentially harmful substances. The constant turnover, it’s thought, is a way to prevent toxic substances from having lasting effects on cells and their offspring.

The crypts that hold ISCs are, in a sense, misnamed. Far from being enclosures where dead cells are entombed, they are the sites where ISCs daily generate the billions of daughter cells that take the place of defunct intestinal cells.

By Extension

The article mentions in passing that “It’s not known whether cells in other organs and tissues have this capability, but it remains an open avenue of investigation.” Logically, it would seem that blood and skin are the next to investigate, since they constantly regenerate new cells. Skin cells were the first tissue cells that Yamanaka used to develop iPSCs.

But what if each organ or tissue could have this capability? The body could live indefinitely, because repairs would be automatic. It would be like each part of a car having the innate ability to return to the raw material from which it was made, and then mold itself back over the damaged part. You would never have to drive to a garage for an external agent (a mechanic) to take out and replace a part. The car could have ‘eternal life’ in a sense.

Monarch butterfly feeding

Credit: Illustra Media

Regeneration is already known in nature. the lowly hydra can be cut and grow back again. Planaria (flatworms) can do this. And insects that undergo complete metamorphosis, like butterflies, return almost to a living ‘soup’ inside the chysalis that transforms into a completely different organism. Some vertebrates, like salamanders, can regrow limbs. It would seem science has much more to learn about regeneration of parts, and maybe ‘de-differentiation’ as observed in the intestine provides a clue.

I am personally grateful for this capability of the intestinal lining. When I underwent cancer surgery, 21 inches of my intestine had to be removed and the cut ends had to be sewed back together. I remember wondering at the time how this occurs, and I worried about leakage or the ends coming apart. My surgeons assured me that within a couple of days it would all be healed up as good as new. Before long I was able to eat again. That’s amazing!

Does this article not shed light on possibilities in the initial creation? Genesis says we live in a world under a curse because of sin. Genesis 3 mentions several immediate changes that exemplified physical aspects of the curse: thorns (degenerate leaves), pain in childbirth, and hard work to make plants grow. The serpent was also cursed to crawl on its belly. Undoubtedly, other changes occurred that made life harder and guaranteed death eventually. Some of these changes may have been explicit as direct judgments from God on the world of sinners yet to be born. Some may have been implicit, such as removal of protections that would make life more difficult, such as disease and decay. At the Fall, Satan also took on the role of “god of this world” to further cause suffering and pain in order to try to thwart the plan of God. Still, as Paul assured the pagans at Lystra, God “did not leave himself without witness, for he did good by giving you rains from heaven and fruitful seasons, satisfying your hearts with food and gladness” (Acts 14:17). And God had a plan to redeem the world.

By inference, none of the curses that make our present world, with its “bondage to corruption” (Romans 8:21-22), were present before sin. It seems conceivable that our bodies were designed to endure with automatic repair and regeneration mechanisms. In mercy, God kept a few – intestines, blood and skin – that otherwise would have ruled out life of any length; after all, people needed to live to adulthood and bear families, because God’s plan included a Redeemer for sin. Genesis also mentions God keeping Adam and Eve away from the Tree of Life, “lest they eat of it and live forever” (in a state of sin). The Tree of Life appears again in Revelation where death is no more.

If heaven (the eternal state for the saved) is not a wispy, ethereal existence but a real, physical reality, then God certainly has the wisdom and omnipotence to create the mechanisms that would make eternal physical life possible. We’re speculating from incomplete knowledge, but perhaps the discovery just made about intestinal stem cells provides a glimpse into “very good” capabilities in the beginning, and credible hopes for an ‘even better’ future life for the redeemed. Have you been redeemed yet? Read this.

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