Stem Cells: Monday, February 23, 2015


The blood cells of mammals are constantly replaced by differentiation a special kind of cell, located in the more central parts of the bone marrow. These are called stem cells. Another kind of stem cell forms the inner germinative layer of the epidermis (the epidermis is the ectodermal part of the skin); this constantly grows and replaces skin cells that die and rub away from the outermost layer of the skin (I refuse to use the word "slough"). Incidentally, the so-called "dust" that accumulates along the tops of picture frames, consists of dead skin cells.

A third example of naturally-occurring stem cells line the stomach and intestine. These constantly divide and replace neighboring cells that have died and broken loose. Sperm cell precursors are another example of stem cells. The word "stem" is used metaphorically, because stem cells are somewhat like stems of a plant, from which new leaves and branches grow.

The defining properties of stem cells have traditionally been unlimited growth and mitotic division, combined with controlled differentiation to replace some particular differentiated cell type.

In the last couple of decades, the phrase "stem cell" has been extended to several other kinds of undifferentiated cells, some of which are artificial, which some scientists believe can eventually be used to replace muscles, bones, nerves and whole organ. Ideally, methods will be discovered by which undifferentiated cells can be grown in tissue culture, to unlimited numbers, and then put back into patients' bodies and caused to differentiate into whatever cell type is missing or needed.

In the new sense of the word "stem cell", any undifferentiated cell that can or might eventually be caused to differentiate will be called a "stem cell", not just the bone marrow cells, germinal layer cells of the skin, etc. It might have been better to invent different words to refer to cells which have been artificially stimulated to lose their differentiation.

If you are interested in how to use propaganda to control people's beliefs and expectations, the history of stem cell biology is full of examples. If you want people to believe that two things are the same, then call them by the same name. Nevertheless, I think that stem cell research will eventually result in medical advances even more important than the ability to transplant bone marrow of graft skin.

Among the obstacles that need to be overcome is muddled reasoning, such as results from using the same term for unrelated, distantly-related or possibly unrelated phenomena. Better names for this subject could have been "de-differentiation research" or "re-differentiation research". To call it stem cell research could give people the idea that what is being studied are bone marrow cells, etc. and how to control their differentiation. That's not the intention. The real intention is to create public and political expectations that because skin and bone marrow can be transplanted, therefore methods can be invented to grow unlimited amounts of any cell type and transplant them into the body.

The "California Institute For Regenerative Medicine" is a more accurate name. But why should we assume that only undifferentiated cells can produce regeneration, or that if we can produce undifferentiated cells, then regeneration will be easy, or even that regeneration will become the slightest bit easier to produce than it is now.

I just read and recommend an excellent and short and sardonic book by Jonathan Slack titled "Stem Cells: A very short introduction" ~$12 & 130 pages. Slack is Director of the Stem Cell Institute at the University of Minnesota, and is a real embryologist who wrote another book that we used as a textbook in this course several years ago.

Here are some quotes from Slack: "Inflated expectations are highly prevalent because we live in a world where money can be acquired by attracting attention and by making promises..."

"The hype has been further amplified by the ethical debate over human Embryonic Stem cells, which has led proponents of stem cell research to promise very rapid development of very rapid cures."

Slack discusses "Aspirational cell therapy, also known as stem cell tourism" as provided by "Doctor Feelgood". He has a few words about the backlash that will come when no breakthrough cures are achieved, despite all the hype.


Recent discussions of "Stem Cells" are mostly about one of the following two:

1) Inner Cell Mass cells dissected out of blastocyst stage mouse or human embryos, and then kept in tissue culture media. These are called ES or Embryonic Stem Cells. Most of the moral controversy is about the destruction of non-viable human embryos to get the inner cell mass cells. Some controversy spilled over to other issues.

2) Induced Pluripotent Stem Cells (iPS cells), which are tissue culture cells whose differentiation has been reduced as much as possible (in any way possible, including insertion of extra copies of 3 particular genes for transcription factors that were previously discovered to be transcribed especially much in undifferentiated cells. Unfortunately, some of these genes can cause cancer.

The first method is to prevent embryonic cells from differentiating, grow lots of them, and then stimulate them to differentiate into insulin-secreting cells, or nerve glia cells, or heart muscle cells, or whatever is needed. Rhetorically, the gimmick has been to imply that these later stages will be easy as soon as better culture methods are discovered to induce growth of inner cell mass cells.

The other method is to choose tissue culture cells (that aren't too aneuoploid, etc.) then use growth-inducing genes to inactivate their differentiation, followed by the same later stages as with the ES cells.


In my opinion, we should be trying to understand regeneration, itself.

Stem cells are not much better than a random guess about how to produce regeneration.




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