Dr. Jill Helms provides a captivating overview of what stem cells are, how they work and what the future may hold for us in this area.
The first topic is "Why do we need regenerative medicine?" She displays an image from a Washington Post article showing a variety of implants and other mechanical devices that are used to replace worn out or broken human parts. But these parts have limitations. For example, hip implants or metal rods in bones fail to have the balance and flexibility that bones have. They can't cushion impact or distribute weight the same way - the result being they are less effective, wear out over time and surrounding tissue is placed at greater risk.
The skeleton replaces itself every 7 years. Defects can be repaired and adjustments can be made.
Tissue and organ transplants have several drawbacks. Low number of available organs. Immune system issues (have to be on immuno-suppressant drugs, which leads to increased cancer risk among the many other problems). That's why organs that aren't absolutely mandatory are rarely transplanted. Identical twins do not need the immuno-suppressant drugs.
IN AREAS WHERE THERE IS CELLULAR DAMAGE THE MECHANISM FOR REPAIR IS DISRUPTED. SCARS AND DAMAGED TISSUE WILL REMAIN BECAUSE THE DAMAGE ITSELF PREVENTS COMPREHENSIVE REPAIR. That's why there's scar tissue to begin with. That's why damaged organs don't heal. That's why stem cell repair is such a potentially great thing, provided it can be started one step removed (i.e. regenerating whole sections, not repairing damaged areas). Basically with the damage, the cells are cut off from nutrients and proteins that promote repair. Once that bridge is blown up, nothing ever travels that way again and the damage remains.
So repair processes can only repair areas when there's access. Cut yourself with a kitchen knife and your cells rush in to fix the damage. Get a recluse bite on that same finger and the tissue withers and dies. The main question is whether there's blood (and nutrients) being supplied. As long as the tissue is accessible, repair can happen.
Weight bearing can help with osteoporosis because the mechanical forces of action signal the body to grow more bone in those weight bearing areas. With bone and hip replacement surgeries, she recommends waiting as long as possible. The areas loosen over time (approximately 15 years) and requires further surgery. With each operation, there's less natural bone to attach the implant to.
Unique feature of stem cells.
1. They can become any cell type in the body. This ability is called pluripotency.
She shows an example of stem cell research with mammary stem cells in mice. The stem cell was tagged with a blue quality so all its "offspring" would be blue and then injected into a different mouse (whose stem cells had been removed). The result was the production of new cells that were blue in the host mouse.
2. They can duplicate themselves.
For example, in bone marrow transplants the marrow of the sick patient is removed by radiation and replaced with donor marrow. The donor marrow then goes on to create all the cells within the bone. The stem cell can create copies of itself and these copies are a complete set, as contrasted with a skin cell making another skin cell but not being able to make any other type of cell.
A difficulty inherent in stem cell use is that it's not always clear what signals the stem cell to create a certain type of cell. DNA coding, transcription factors, etc. influence the stem cell's expression, but we haven't yet mastered how to make this happen on demand.
Embryonic stem cells come from a morula, which is formed nearly right away (about 5 days). They come from the blastula. They are before tissue (they form the tissue). A difficulty in cultivating these lines is that in order to make them grow, they need nutrients. The feeder layer they are placed on can eventually alter the stem cell line.
Newts and regeneration. A wound blastema forms at the tip of the amputated limb. Stem cells flood into the blastema from nearby muscle, cartilege and nervous tissue. The limb them regenerates. They seem to have an unlimited number of stem cells (whereas we seem to have a limited number).
Repair vs. regeneration. After a serious wound, we don't regenerate, we repair. Scar tissue takes over. Scar tissue has different functionality and lacks many of the characteristics of the original tissue. It might be this way because it is a way to cover the wound quickly. However, scar tissue sucks in many ways. After a spinal cord injury scar tissue replaces the original tissue and can result in paraplegia. Post stroke, glial scar tissue covers over affected areas of the brain, essentially killing off the neurons. A heart attack results in scar tissue in the heart which interferes with the heart's functioning (this is why major heart surgery is known as bypass surgery - the surgical team has to create a new pathway for blood flow since the old has been compromised).
The human liver has enormous regenerative capacity. Up to 25% can be removed and will regrow. As long as scar tissue isn't formed. If there's scar tissue you have cirrhosis and it will not regrow. Professor Helms notes that you have to form the blastema to have regrowth (and you can even transfer the blastema to another part of the body and it will grow the limb or organ it was originally planning on growing). What this suggests is that stem cell success may end up being more about replacing entire organs (heart, liver, kidney transplants) than site repair. Cloning is making an identical copy of a cell, organ or being.
In 1958 an entire carrot was formed from a single cell via cloning technology. The first animal was a frog. A fully differentiated cell, when placed into another area, will continue growing its type of cells. However, if the nucleus is extracted and placed into another area, it will grow the new area's type of cells. So the nucleus contains the info for all cell types. What this ultimately suggests is that regenerative growth is very much about how to turn on a particular DNA coding sequence. So you can take a fully differentiated skin cell and by introducing these genes (Oct4, Sox2, Klf4 and c-Myc/nanog) you can turn it back into a stem cell. This is done by introducing the genes into a virus which is then introduced into the nucleus. (As a side note, c-Myc is a proto-onco gene, meaning it can form a cancer - again, that's growth). Recent research has even shown that the virus may not be needed; the proteins can be used instead.
Next she suggests that adult cells may not be expressing the right growth factors to keep stem cells alive and to promote regenerative growth. My sense is that this is an inaccurate point - we have to go back to the question of scar tissue and nutrient supply. As long as the blood is flowing to an area, it has the potential for healing and the growth factors will be expressed. Once the area is cut off it dies. You can't send a pothole repairman to fix a collapsed bridge.
Stem cells must still follow the right differentiation pathway. Otherwise you have a major cancer risk.
Newcastle disease, virus growth within a petri dish and the development of sufficient polio for study and eventual vaccination. An "initial" difficulty was that the virus wasn't infecting test cells in petri dishes enough to allow for comprehensive study. Salk piggybacked some of his research on the methods used for the study of Newcastle disease and was able to get more polio growth for study. (The latency of polio viruses in cell cultures and monkey trials would later re-emerge as an issue when several pharmaceutical companies, most notably Cutter Laboratories, created and released their vaccinations. Vaccinations from Cutter contained live polio virus and infected thousands of patients, with over a hundred suffering paralysis.)
Fruit fly research, wingless flies led to discovery of wynt, which is involved in bone production, neural stem cells and hair regrowth too.
Too much wynt = van Buchem disease (super thick bone). Too little wynt = bone loss. So in the event of bone injuries, especially in susceptible populations (the elderly, people with cancer), the use of wynt technologies can facilitate bone repair and growth. The stem cells within the injury area respond to wynt by proliferating. So for the 82 year old grandmother with a broken hip, fruit fly research can be the difference between mobility and being in a wheelchair, or worse.
The first topic is "Why do we need regenerative medicine?" She displays an image from a Washington Post article showing a variety of implants and other mechanical devices that are used to replace worn out or broken human parts. But these parts have limitations. For example, hip implants or metal rods in bones fail to have the balance and flexibility that bones have. They can't cushion impact or distribute weight the same way - the result being they are less effective, wear out over time and surrounding tissue is placed at greater risk.
The skeleton replaces itself every 7 years. Defects can be repaired and adjustments can be made.
Tissue and organ transplants have several drawbacks. Low number of available organs. Immune system issues (have to be on immuno-suppressant drugs, which leads to increased cancer risk among the many other problems). That's why organs that aren't absolutely mandatory are rarely transplanted. Identical twins do not need the immuno-suppressant drugs.
IN AREAS WHERE THERE IS CELLULAR DAMAGE THE MECHANISM FOR REPAIR IS DISRUPTED. SCARS AND DAMAGED TISSUE WILL REMAIN BECAUSE THE DAMAGE ITSELF PREVENTS COMPREHENSIVE REPAIR. That's why there's scar tissue to begin with. That's why damaged organs don't heal. That's why stem cell repair is such a potentially great thing, provided it can be started one step removed (i.e. regenerating whole sections, not repairing damaged areas). Basically with the damage, the cells are cut off from nutrients and proteins that promote repair. Once that bridge is blown up, nothing ever travels that way again and the damage remains.
So repair processes can only repair areas when there's access. Cut yourself with a kitchen knife and your cells rush in to fix the damage. Get a recluse bite on that same finger and the tissue withers and dies. The main question is whether there's blood (and nutrients) being supplied. As long as the tissue is accessible, repair can happen.
Weight bearing can help with osteoporosis because the mechanical forces of action signal the body to grow more bone in those weight bearing areas. With bone and hip replacement surgeries, she recommends waiting as long as possible. The areas loosen over time (approximately 15 years) and requires further surgery. With each operation, there's less natural bone to attach the implant to.
Unique feature of stem cells.
1. They can become any cell type in the body. This ability is called pluripotency.
She shows an example of stem cell research with mammary stem cells in mice. The stem cell was tagged with a blue quality so all its "offspring" would be blue and then injected into a different mouse (whose stem cells had been removed). The result was the production of new cells that were blue in the host mouse.
2. They can duplicate themselves.
For example, in bone marrow transplants the marrow of the sick patient is removed by radiation and replaced with donor marrow. The donor marrow then goes on to create all the cells within the bone. The stem cell can create copies of itself and these copies are a complete set, as contrasted with a skin cell making another skin cell but not being able to make any other type of cell.
A difficulty inherent in stem cell use is that it's not always clear what signals the stem cell to create a certain type of cell. DNA coding, transcription factors, etc. influence the stem cell's expression, but we haven't yet mastered how to make this happen on demand.
Embryonic stem cells come from a morula, which is formed nearly right away (about 5 days). They come from the blastula. They are before tissue (they form the tissue). A difficulty in cultivating these lines is that in order to make them grow, they need nutrients. The feeder layer they are placed on can eventually alter the stem cell line.
Newts and regeneration. A wound blastema forms at the tip of the amputated limb. Stem cells flood into the blastema from nearby muscle, cartilege and nervous tissue. The limb them regenerates. They seem to have an unlimited number of stem cells (whereas we seem to have a limited number).
Repair vs. regeneration. After a serious wound, we don't regenerate, we repair. Scar tissue takes over. Scar tissue has different functionality and lacks many of the characteristics of the original tissue. It might be this way because it is a way to cover the wound quickly. However, scar tissue sucks in many ways. After a spinal cord injury scar tissue replaces the original tissue and can result in paraplegia. Post stroke, glial scar tissue covers over affected areas of the brain, essentially killing off the neurons. A heart attack results in scar tissue in the heart which interferes with the heart's functioning (this is why major heart surgery is known as bypass surgery - the surgical team has to create a new pathway for blood flow since the old has been compromised).
The human liver has enormous regenerative capacity. Up to 25% can be removed and will regrow. As long as scar tissue isn't formed. If there's scar tissue you have cirrhosis and it will not regrow. Professor Helms notes that you have to form the blastema to have regrowth (and you can even transfer the blastema to another part of the body and it will grow the limb or organ it was originally planning on growing). What this suggests is that stem cell success may end up being more about replacing entire organs (heart, liver, kidney transplants) than site repair. Cloning is making an identical copy of a cell, organ or being.
In 1958 an entire carrot was formed from a single cell via cloning technology. The first animal was a frog. A fully differentiated cell, when placed into another area, will continue growing its type of cells. However, if the nucleus is extracted and placed into another area, it will grow the new area's type of cells. So the nucleus contains the info for all cell types. What this ultimately suggests is that regenerative growth is very much about how to turn on a particular DNA coding sequence. So you can take a fully differentiated skin cell and by introducing these genes (Oct4, Sox2, Klf4 and c-Myc/nanog) you can turn it back into a stem cell. This is done by introducing the genes into a virus which is then introduced into the nucleus. (As a side note, c-Myc is a proto-onco gene, meaning it can form a cancer - again, that's growth). Recent research has even shown that the virus may not be needed; the proteins can be used instead.
Next she suggests that adult cells may not be expressing the right growth factors to keep stem cells alive and to promote regenerative growth. My sense is that this is an inaccurate point - we have to go back to the question of scar tissue and nutrient supply. As long as the blood is flowing to an area, it has the potential for healing and the growth factors will be expressed. Once the area is cut off it dies. You can't send a pothole repairman to fix a collapsed bridge.
Stem cells must still follow the right differentiation pathway. Otherwise you have a major cancer risk.
Newcastle disease, virus growth within a petri dish and the development of sufficient polio for study and eventual vaccination. An "initial" difficulty was that the virus wasn't infecting test cells in petri dishes enough to allow for comprehensive study. Salk piggybacked some of his research on the methods used for the study of Newcastle disease and was able to get more polio growth for study. (The latency of polio viruses in cell cultures and monkey trials would later re-emerge as an issue when several pharmaceutical companies, most notably Cutter Laboratories, created and released their vaccinations. Vaccinations from Cutter contained live polio virus and infected thousands of patients, with over a hundred suffering paralysis.)
Fruit fly research, wingless flies led to discovery of wynt, which is involved in bone production, neural stem cells and hair regrowth too.
Too much wynt = van Buchem disease (super thick bone). Too little wynt = bone loss. So in the event of bone injuries, especially in susceptible populations (the elderly, people with cancer), the use of wynt technologies can facilitate bone repair and growth. The stem cells within the injury area respond to wynt by proliferating. So for the 82 year old grandmother with a broken hip, fruit fly research can be the difference between mobility and being in a wheelchair, or worse.