Logistical Barriers to Stem Cell Researchby Sajid Surve, DO | March 1, 2009
I recently attended a lecture by Wise Young, MD, PhD, who is a prolific researcher in the fields of spinal cord injury and stem cells. The lecture was fascinating, and part of the discussion was the current model for stem cell research. Currently we have two types of stem cells which are available for study: embryonic stem cells and induced pluripotent stem cells (iPSCs). As is well known, embryonic stem cells are derived from fertilized embryos that are allowed to multiply briefly before the cells are harvested. iPSCs are precursor cells found in adults, which are then chemically treated to revert them back to a stem cell.
To better understand this topic, one needs a little background in embryology. Once an embryo is created, the cells begin to multiply and differentiate into all the other types of cells that we have in our bodies. At the very early stages, the cells are lumped into 3 layers, called the ectoderm, mesoderm, and endoderm. Cells in each of these layers then move on to further differentiate into precursor cells, which then differentiate further into our final cell types. The ectoderm is what eventually differentiates into our skin, as well as our brain and spinal cord. The mesoderm differentiates into bone, muscle, and cartilage, as well as our heart, blood, blood vessels, and reproductive organs. The endoderm is responsible for forming our internal organs. Generally speaking, once a cell is designated into one of these 3 layers, it is committed to becoming a cell within those parameters. A mesodermal cell could not become a hair follicle, and an ectodermal cell could not become part of the liver.
Once we have been fully differentiated and are functional human beings, the stem cells do not disappear. They stay in small quantities around the structures they formed. Ectodermal stem cells are still present in the skin and brain. Mesodermal stem cells are still present circulating in the blood and bone marrow. Endodermal stem cells reside in the internal organs. They continue to produce precursor cells, which are then useful in tissue repair. As an example, the mesodermal stem cell can produce fibroblasts, which are precursor cells that lay down collagen for use in bones and connective tissue.
Currently, stem cell researchers are only able to control ectodermal and mesodermal cells. Science has not yet devised a way to control the differentiation of endodermal cells. This fact means that organ diseases such as diabetes or hepatitis are not being studied for stem cell cures. However, through chemical treatment, researchers have found a way to convert a mesodermal stem cell into an ectodermic stem cell and vice versa. They have also found a way to take precursor cells and revert them back to stem cells. In a practical example, this is significant because now scientists could take a skin cell, chemically revert it back into an ectodermal stem cell, convert it into a mesodermal stem cell, then redifferentiate it into a blood precursor to treat blood diseases. This process is what is meant by iPSCs.
Embryonic stem cells are a difficult thing to maintain. They are built to differentiate, not to remain as stem cells. The process to take an embryonic stem cell and ensure that it remains the same is tedious and laborious, requiring both manpower and money. If the process is not carried out perfectly, then all the stem cells will convert and the researcher is left with nothing. By contrast, iPSCs are produced on demand. If some mesodermal stem cells are required, they can be harvested out of the blood or bone marrow, or chemically produced from skin cells as outlined above. The downside is that the technology is fairly new and not able to be done except in a few highly specialized labs. That means that for now, most research is being carried out on embryonic stem cells until the iPSCs are easier to produce.
In terms of availability, the majority of current embryonic stem cells are being harvested in blood banks and umbilical cord blood banks. The problem is that the vast majority of umbilical cord blood banks are private, meaning the blood is frozen and maintained separately, not available to researchers. Of all the blood that resides in private cord blood banks, less than 1% is ever used. Cord blood samples are so rarely used or tested, in fact, that it is unclear how long cord blood can be maintained in a frozen state, or if it will be viable when the thawing process is complete. Private blood samples are also not indexed or released to the national stem cell databanks, meaning that a potential stem cell recipient would never know that they had a perfect match sitting in a private bank.
In the near future, Dr. Young predicted that the way we process, access, and research stem cells will radically change. Once a commercially viable process to produce iPSCs is perfected, the need for embryonic stem cells will disappear. People could submit a swab from the inside of their cheek, and a week or two later receive a plastic bag filled with ectodermal or mesodermal stem cells for use in transplantation or research. Cracking the code of endodermal stem cells will also dramatically increase the range of diseases that stem cells have the ability to treat. Until that time, we have no choice but to look to the future with optimism and wait patiently.
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