Chapter 1
Meet Your Stem Cells
Stem cell technology represents one of the most astonishing new developments in medicine in a century. Treatments based on stem cells have the potential to tackle many of the most troubling diseases and injuries that we might face during our lives. However, our own intrinsic populations of so-called “endogenous” stem cells are vital and need attention as well. They have underappreciated, but huge roles in our everyday health, reproduction, and aging.
As you are reading this you have endogenous stem cells in every part of your body busily working away to maintain your body and as a result your health.
Stem cells in the eyes reading these words.
Stem cells in the hands turning the page.
Stem cells in the stomach digesting your food as you read.
And so forth.
Answers to many of the most critical questions about stem cell medical treatments of today and the future come from studies of these endogenous populations of stem cells that we each already possess. In addition, some of the most essential lessons about stem cells that researchers such as myself have learned come from studies of endogenous stem cells and models developed from them. Therefore, to start this book I will introduce you in this chapter to your stem cells from the perspective of an insider.
The idiosyncrasies, strengths and shortcomings of our own unique cohorts of stem cells are key determinants for how we age and our health along the way. Unfortunately, our stem cells are not perfect. Their limitations point to the reasons why potential stem cell transplants are so significant as a new form of medicine. Stem cells with significant clinical potential include embryonic stem cells, fetal stem cells, adult stem cells, and induced pluripotent stem (iPS) cells. The last is a remarkable new kind of designer stem cell that has nearly all of the properties of embryonic stem cells, but does not require an embryo to make.
What are Stem Cells?
Before we get too far into our discussion of different kinds of stem cells including our own endogenous stem cells, we need to address a fundamental question:
What are stem cells?
I will let you in on a secret. Even stem cell scientists sometimes argue with each other about whether certain cells qualify as “stem cells”.
The old saying about a duck that if something walks like a duck and quacks like a duck, it is a duck, does not entirely work when it comes to cells. Appearances can be deceiving.
Cells can “walk” like a stem cell, meaning behave akin to a stem cell, and still not be a stem cell. A cell can also quack or “talk” much like a stem cell (meaning present itself via markers and gene expression as a stem cell) and still not always be a stem cell.
Cells generally speaking are far more difficult to distinguish from each other than most people may realize and the same is true of stem cells specifically. Why? Most cells look almost identical and do not always behave in a manner that immediately tells a scientist or medical doctor that they are a stem cell. Any given stem cell does not have the molecular equivalent of “stem cell” tattooed on its outer membrane. As a result, even scientists are not always entirely sure if specific cells are stem cells or alternatively some other related kind of cell such as progenitor cells. For example, some non-stem cells just have some, but not all the qualities of stem cells.
Time also can be a critical factor.
Cells can change their identities over time. As a result, certain cells can be stem cells one day and then the next not be stem cells any more. It is even formally possible that non-stem cells can revert back to be stem cells later on in their cellular life history. The ability of non-stem cells to be forced by scientists to become stem cells again in vitro in a lab and even in vivo in mice has been beautifully illustrated in the case of iPS cells [1], which garnered a stem cell researcher, Shinya Yamanaka, the Nobel Prize in 2012. iPS cells will be discussed in a great deal more depth later in this book. Whether this phenomenon of a non-stem cell changing back into a stem cell occurs naturally remains unknown. However, the point is that cells, including stem cells, exist in a state with a given identity for only a finite period of time. They are dynamic.
Still, despite the complexities, scientists usually agree on what defines a stem cell. A stem cell has two key properties. First, it possesses “self-renewal”, which simply means that it can divide to make more stem cells. Second, a stem cell has “potency” meaning it can differentiate into a variety of other cell types. A true stem cell has both self-renewal and potency.
What Do Stem Cells Do?
Our bodies are made up of different building blocks of various sizes. One human body is made of many organs such as the brain, the heart, the liver, and so forth. Each of these parts is made up of tissues, which are relatively smaller. In turn tissues are made of cells. While one can go even smaller to molecules, it is cells that are the smallest well-defined building blocks and functional units of the body.
A very large fraction of our cells are akin to Legos™. They are structural units that make up the mass of the tissues and organs of the body. In addition, many other cells have more dynamic functions rather than just strictly being building blocks. Certain cells of the heart beat. Brain cells such as neurons work together to make us think. Beta cells of the pancreas make insulin to regulate appropriate blood levels of sugar. Taken all together, the structural and functional cells constitute 99% or more of all the trillions of cells in one human body.
Most of cells within the remaining 1% population are so-called progenitors, which are the immediate source of substitutes for the other 99% should they wear out, be damaged or die. Think of an analogy to a sports team. When a player gets injured on the field, in runs the substitute or “sub”. When it comes to cells, that sub is sourced directly or indirectly (via progenitors) from pools of stem cells contained within every tissue.
The body has mechanisms for sensing cell damage or death, which triggers stem and progenitors to proliferate and differentiate into fresh supplies of specialized cells. However, the progenitor cells are limited in what they can do and they also wear out. The ultimate supply source for all cells in our body is stem cells. Through potency and self-renewal, it is stem cells that are responsible for keeping our body healthy and fully- staffed with cells and tissues.
The battalions of endogenous stem cells in our bodies number in the millions for specific tissues, which seems like a big number until you recall that our bodies have trillions of cells. Day-in and day-out, stem cells acting as tiny defense forces achieve things that in the transplant world of stem cells are only a stem cell doctor’s dream. In every organ of your body stem cells lay in waiting for the time when you get hurt or sick. Injury or disease is their bugle call. They spring into action and working as a microscopic army of doctors, they pay the ultimate house call inside of our bodies. How these endogenous stem cells function helps us scientists predict how transplanted stem cells, emerging as a new type of medicine, will behave in recipient patients. The hope is that the transplanted stem cells will behave akin to our endogenous stem cells, or perhaps even better and stronger.
The best examples of how stem cells function come from everyday life, even though we do not consciously think of our stem cells routinely helping us. Pull a muscle at the gym? It is your own stem cell “doctors” that fix that. Scrape your elbows and knees after crashing while cycling? Ever wonder how your skin gets better in a matter of days? Most of us do not even give this healing a second thought in terms of how it works even though it is somewhat miraculous. The answer is that your own platoon of skin stem cells mobilizes and acting together as micromechanics they fix you up with new skin at the same time your bike is getting fixed at the shop.
Imagine your surprise if you left your wrecked bike in your garage instead of taking it to the bike shop and a few days later you found that it had fixed itself? That would be amazing, but why then are we not impressed when our body fixes itself?
If you think about it the body’s ability to heal itself, which is a stem cell-dependent process, is rather striking. We do not have to think to ourselves “Okay, I better heal myself” and go through in our minds the steps involved, consciously coordinating the process. In fact, we are not capable of doing that. Instead, our stem cells just automatically do it for us because that is what they are programmed to do. In this book we are going to talk a great deal about that stem cell programming.
It is not just injuries that stem cells work to address, but also pathogen-based illnesses as well. Get sick with a virus? Bacteria get under the skin after that bike accident? The only reason you get better is because of stem cells that supply your immune system. Without them, even something as benign as the common cold could prove fatal. When you get sick or injured regardless of where this happens in your body, your stem cells are there to come to the rescue by powering and coordinating the repair of the affected area.
A Stem Cell Fountain of Youth?
Another compelling, potential attribute of our stem cells is that they not only fix disease and injury, they also are thought to constantly fight aging. Together endogenous stem cells constitute a very real, miniature version of The Fountain of Youth that we all carry around with us.
Remarkably, without the system of stem cells throughout every part of our bodies, all of us would rapidly age and die within a period of only weeks or months. For example, if I suddenly lost all the stem cells in my body, within months I would have nearly no immune system as almost all of its cells would die as they normally do, but there would be no replacements. Not only would I be helpless against any major pathogen that I might be exposed to, but also everyday bumps and bruises as well as simple things such as a small cut could turn deadly for me.
More broadly, besides resupplying the immune system, stem cells also keep us young by replacing our injured or dying cells with new, young ones throughout the body. This very normal process is called “homeostasis”. In the human body it is standard procedure for billions of cells to die and be replaced with new, healthy ones every day. For this reason, your hypothetical stem cell-less author would not only get sick, but also I would age at fast-forward speed. Therefore, if miraculously, illness or injury did not get me, I would quite literally die of old age within a few years or less. The same thing would happen to you if you lost your stem cells.
Sadly, losing one’s stem cells is not just a hypothetical event. There are real diseases that foul up our ability to replace stem cells, leading to accelerated aging of the hypothetical kind that I described above. Generally, these rapid aging syndromes are called “Progeria”, which comes from the Greek Progeros meaning “prematurely old”. The suffix “geria” means “old” and is used as a prefix to...