There are many types of stem cells. Stem cells are found everywhere in the body. They may be grouped according to where they came from (Tissue type) and developmental stage (Embryonic or adult), ability to grow in a test tube, Manipulation (Minimal or cultured), or ease of differentiation in a test tube (Totipotent, pluripotent, multipotent, unipotent). Mesenchymal stem cells are proving to be the easiest and most useful of the stem cells that we have available.
Ease of differentiation (Totipotent, Pluripotent, Multipotent or Unipotent etc) is less important than we first thought since we now know that any cell can become any other cell. Just as we can do it in a test tube the body seems to do it with ease.
| Totipotent | Embryonic | Embryo |
| Pluripotent | Adult (Somatic) | Adipose, Bone Marrow, Umbilical, etc |
| Multipotent | Tissue type (Lineage) | Neural – make neurons, astrocytes, oligodendrocytes. |
| Unipotent | Single cell (Precursor) | Endothelial progenitor cell (EPC) |
Embryo and development.
As the embryo develops it forms three germ layers. Endoderm on the inside, mesoderm in the middle and ectoderm on the outside.
- Endoderm forms the stomach, colon, urinary bladder, lungs.
- Mesoderm forms muscle, bone, cartilage, blood vessels, joints, connective tissue, endocrine glands, kidney cortex, heart muscle, urogenital organ, uterus, fallopian tube, testicles and blood cells from the spinal cord and lymphatic tissue
- Ectoderm forms hair, nails, nerve tissue, outer layer of skin, salivary and mucous glands
These three layers interact with each other to form all the organ systems of the body as well as a special connective system called mesenchyme which supports them all. Mesenchyme is present in every tissue. The stem cells in mesenchyme are called mesenchymal stem cells. Each tissue also has its own specialised stem cell. The brain has neural stem cells, the kidney has renal stem cells, bone marrow has hematopoietic stem cells for making blood cells as well as Mesenchymal Stem Cells. Even the cornea of your eye has mesenchymal stem cells (Ref)
Mesenchymal Stem Cells
The role of the mesenchyme as a supporting connecting tissue throughout the body helps us to understand why mesenchymal Stem Cells have been so successful in healing and replacing damaged and diseased tissues all over the body. A prime function of mesenchymal stem cells is the formation and healing of blood vessels. This allows nutrients to reach impoverished tissues, and waste products to be removed. Once the vascular supply has been restored the specialised stem cells (eg renal stem cells) that are already in the tissue will be able to get back to doing what they normally do and the tissues can heal themselves.
Hematopoietic Stem Cells
Ogawa and his team at the laboratory of the Medical University of South Carolina have done a lot work exploring the origin of Hematopoietic stem cells and how that demonstrates the ‘plasticity’ of Hematopoietic Stem Cells. Plasticity is the ability of one cell to change and become another. This is one of the things that sets stem cells apart from other cells. They go on to state that “HSCs are not just “hematopoietic,” but are pluripotent. HSCs may support regeneration of the majority of, if not all, cells in our body.”
inducedPluripotent Stem Cells (iPSC)
We used to believe that cells changed (differentiated) in one direction only moving from stem cells to totally specialized cells such as a skin cell and that was the end. Then in 2006 Shinya Yamanaka and Kazutoshi Takahashi changed a mature skin cell back into an embryonic cell (induced Pluripotent Stem Cell)
This demonstrated that cells could change in any direction to become any other cell.
So is any one cell type better than another if they can all change? Hematopoietic Stem cells can become Mesenchymal Stem cells, and mesenchymal Stem Cells can become Hematopoietic.
Advantages and disadvantages of Stem Cell Types
There are many ‘advantages’ proposed for one cell type over another. Do you want to use your own stem cells or someone elses
Autologous (Using your own stem cells)
Stem cells are found in almost every tissue. In your eye the edge of the cornea is the limbus. This is where corneal limbal stroma stem cells are found. Human dental tissue-derived mesenchymal stem cells are found in your teeth. Stem cell numbers in these locations are very low. Bone marrow contains much larger numbers, and adipose tissue has 500x more MSCs than bone marrow, and most people have very generous supplies of fat. This makes adipose a clear winner if you want lots of cells.
Horinouchi et al tested the ablility of stem cells from young people and old people. They showed that both groups multiplied at the same speed and were equally able to grow into bone, cartilage or fat cells. So your fat derived stem cells stay young even though you are getting older.
Yamagouchi et al found that this did not hold true for rats. Rat fat appears to age at the same rate as the rest of the rat.
Cultured stem cells
Stem cells can be grown in culture. This does allow us to get large numbers of different kinds of our own stem cells but it comes with increased manipulation (Manufacturing), cost and risk.
When we harvest a tissue it contains many different stem cell types and stem cells of different potency. Culturing (Cloning) stem cells reduces the mixture of stem cells that were collected down to only one type of stem cell. Your body has many different cell types in each tissue and organ. Arteries, nerves, bone, muscle, etc. They all are damaged in each disease. It is logical that we would improve our results if we can treat multiple diseased cell types with multiple stem cell types in large numbers.
Stem cells have been shown in a test tube to be able to grow from one cell type into every other cell type. What happens in a test tube is very different to what may happen in the human body. In a test tube we will add a small number of hormones, minerals or cytokines so that we can measure the effect they have on stem cells in isolation. When we place these cells inside the body they are exposed to literally thousands of signals and messages asking for help or telling them what is happening in the tissues around them and in far distant locations. This makes it very difficult to compare what we have seen in a test tube to what will happen in a very busy, lively body.
Growing too many cells
Concern has been expressed that stem cells could make too much bone or too many arteries, or too many of any cell or tissue type but it would appear that stem cells are not self directed but that they respond to what the body asks for. If the oxygen tension is too low the stem cells grow blood vessels. When the oxygen levels rise the stem cells stop growing blood vessels and move on to the next task..
Mobility
Fresh uncultured Mesenchymal stem cells are very mobile and able to move to the far ends of your body. When we inject knees we also inject into a vein. These cells travel across the lungs into arteries and are taken everywhere arteries go. Cultured stem cells are larger and stiffer and cannot pass through the lungs in large numbers. (Pulmonary first pass effect). Our patients report improvements in multiple locations including the brain when we use uncultured cells. Uncultured cells will cross the blood-brain barrier. They see reduced headaches, better memory, etc.
We are starting to see trials comparing different cell types and eventually we will know how important or unimportant these choices are.
Minimal manipulation
There is a lot of conflicting information available about stem cells. It is the same for diets. Fortunately we have been researching diets for thousands of years and in the last few decades we have made some good progress. Consensus is moving toward less processed is best. Simple is better.
Stem cells are very likely to follow the same path. The less we interfere and leave the body to direct things the safer we may be. Adipose Stromal Vascular Fraction and Bone Marrow aspirate are both minimally manipulated and are showing powerful responses for various diseases.
Allogeneic
These are cells from another member of the same species. Getting cells from someone else raises many concerns and needs a lot more understanding on the part of the patient and a lot more care on the part of the donor, the technicians and the doctor. The hope for the future is that they can be manufactured in extremely large numbers so that the cost can be reduced for patients. Cheap, safe and effective stem cells in large numbers is still a distant dream.
Complying with regulations (safeguards) is very expensive as we see when trying to find new drugs. Making sure they are safe takes lots more money and when first marketed new drugs are very expensive. The same principles apply to stem cells but stem cells are still a long way behind drug discovery.
Donor selection
Donors are carefully screened for genetic defects and communicable diseases. Stem cells are immune privileged. That means that cross matching is not needed unless you intend to use large numbers of cells which raises a risk of the donor cells trying to take over. (GVHD)
Comparing adult stem cells from different sources reveals a pattern of increased vigor and ability to multiply in test tubes as we move closer to the embryo. Placental and umbilical stem cells perform very well in the test tube. How important this is will only become apparent once we are able to run head to head trials comparing different cell types.
In most countries stem cells are only available in clinical trials.