Stem cell research is hot, and getting hotter. Big deal, you might think. This esoteric topic may be important for some scientists, or maybe a few politicians—but what’s in it for me? Let me tell you right off: A lot more than you can imagine. Just consider the statistics, and do the math of your odds of, one day, requiring stem cell therapy.

Heart disease:

  • Almost 1 out of every 2.4 deaths in the USA result from cardiovascular disease, or CVD.
  • Since 1900, CVD has been the leading cause of death in every year but one, in 1918. In that year, the main cause of death was the Spanish Flu pandemic.
  • About every 29 seconds, an American will suffer a coronary event.
  • About every 60 seconds, someone dies from one.
  • At least 250,000 people die of heart attacks each year before they reach a hospital.
  • It is a myth that heart disease is a man’s disease. In fact, cardiovascular diseases are the number one killer of women (and men). These diseases currently claim the lives of more than a half a million females every —yearmore than the next 16 causes of death put together.

Diabetes (type 2):

  • As of 2005, 20.8 million people—7.0% of the population—had diabetes; according to recent CDC figures, there are approximately 798,000 new cases of type 2 diabetes annually in the USA, most are Type 2 diabetes.
  • According to the WHO figures, there were 173 million cases of type 2 diabetes worldwide in 2002.
  • Type 2 diabetes confers a two to four-fold greater risk of coronary heart disease among men and a three to five-fold increased risk among women.
  • Diabetes also magnifies the effect of raised cholesterol levels, raised blood pressure, smoking, and obesity and so, influences coronary heart disease risk indirectly.
  • Number of deaths with diabetes as the underlying cause of death climbed from 34,500 in 1980 to 62,000 in 1996—an increase of over 44% in 16 years.
  • Diabetics use medical resources at a higher rate than average, nationwide. Diagnosed diabetics constitute about 7% of the total population, but diabetes costs account for about 13-14% of all healthcare expenditures. Diabetes treatment costs about $113 billion a year—more than three and a half times as much as the care for non-diabetic patients.

Alzheimer’s disease:

  • There are now more than 5 million people in the United States living with Alzheimer’s. This number includes 4.9 million people over the age of 65 and between 200,000 and 500,000 people under age 65 with early onset Alzheimer’s disease and other dementias. This is a 10% increase from the previous prevalence nationwide estimate of 4.5 million.
  • Every 72 seconds, someone develops Alzheimer’s.
  • Without a cure or effective treatments to delay the onset or progression of Alzheimer’s, the prevalence could soar to 7.7 million people with the disease by 2030. By mid-century, the number of people with Alzheimer’s is expected to grow to as many as 16 million, more than the current total population of New York City, Los Angeles, Chicago, and Houston combined.
  • As the prevalence impact of Alzheimer’s grows, so does the cost to the nation. The direct and indirect costs of Alzheimer’s and other dementias amount to more than $148 billion annually, which is more than the annual sales of any retailer in the world excluding Wal-Mart.

Parkinson’s disease

  • There are about 1.1 million people in the U.S. diagnosed with Parkinson’s disease. This is a rate of about 360 per 100,000 people. The rate for people over 65 is about 3%.
  • The most detailed report on the economic impact of PD was prepared in 1998 for the Parkinson’s Disease Foundation. This study estimated the per-individual yearly cost of PD in 1997 at $24,041 ($24,425 in 1998). Based on a prevalence of one million affected individuals, the total economic burden was calculated at $24 billion.

So there you have it. I listed only four diseases that may be amenable to stem cell therapy. The reason I included the costs of these diseases is to highlight the cost to you, in the form of healthcare insurance and direct costs, before you die.

 

What is a stem cell?

Just think of it as the stem of a plant, which gives rise to the branches and leaves. The developing embryo is formed by a few cells that have the potential to develop into any of the body’s almost 200 cell types. We call such cells “pluripotential”. And when their origin is from an embryo, they are called “embryonic pluripotential cells”. It turns out that every fully formed tissue—be it blood, neurons, heart—maintains a small reservoir of pluripotential cells, albeit less “pluri” than the embryonic ones, because they are destined to develop into only one or a few specific tissues. This is biology’s form of insurance, in case a certain tissue is in need of repair or regeneration. Alas, in the course of evolution, we lost our capacity to regenerate new heart muscle or new brain cells, although the cells are still there, dormant.

The big debate the country went through was over the use of cells derived from a (discarded) blastula (an early stage of embryonic development, consisting of a spherical layer of around 128 cells surrounding a central fluid-filled cavity). Some people saw it as tantamount to murder; others saw the tilting of the moral balance in favor of a discarded agglomeration of 128 cells over the suffering of millions of living people as incomprehensible, if not unconscionable.

 

The new discovery: Genetically manufactured stem cells

Last week, Shinya Yamanaka of the University of Kyoto reported that his team has created pluripotent cells from human skin cells, or fibroblasts. On the same day, a team of researchers led by James Thompson at the University of Wisconsin, Madison, reported the same. Do you get the sense that there must have been a fierce race underway to reach this goal? You are absolutely right. Here is what happened.

Last year, Yamanaka discovered that introducing four proteins called transcription factors into mouse skin cells “reprogrammed” the cells into an embryo-like state. There are thousands of different transcription factors in every cell nucleus, and their function is to regulate gene expression. The discovery that only four transcription factors can induce such a profound change in the character of a cell is astounding. But this was in mouse, and there are basic differences between human and mouse cells. Yamanaka knew that his publication would trigger an intense race to accomplish the same feat in human cells. He worked 16 hours a day, seven days a week, and reported last week that the same four factors produced the same results in humans. The cells were taken from the face of a 36-year-old Caucasian woman. He repeated the exercise with cells from joint fluid from a 69-year-old man with similar results.

Back in Madison, James Thompson read Yamanaka’s mouse experiment with more than passing interest. After all, he was the discoverer of the method to propagate human embryonic stem cells. He immediately set out to repeat Yamanaka’s experiments in human cells, with two differences. The first was the source of the skin cells: He obtained them from foreskin, which is fertile ground for a lot of internet jokes but is otherwise of no import. The other difference is important; he used four transforming factors, but only two of the ones used by Yamanaka. He avoided one factor, c-myc, because it is associated with cancer. The fact that he could use different transforming factors suggests that in the future, scientists will have great latitude in the formation of “induced pluripotent stem (iPS) cells”, maybe of different traits and capabilities.

 

The future is bright

These were the first two teams to reach the finish line. Many more are still racing. With researchers crowding into the field, rapid advancements are certain. As several scientists ecstatically stated, this is a paradigm shift in reprogramming cells, and will relatively soon result in patient-specific pluripotent cell therapy. Many obstacles remain, but all are surmountable; the big breakthrough has been accomplished. The grim statistics of heart disease, diabetes, neurological diseases, and probably cancer will become a lot less menacing.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.