The Current Stem Cell Therapy
What Makes a Stem Cell? (1:04 – 6:50)
There are three qualities that qualify something as a stem cell. A stem cell should be able to self-renew and this is where a cell divides in an asymmetrical division. Every time a cell divides, one of the cells will have the exact properties of the original cell and have the ability to differentiate itself from a particular tissue. When a tissue is injured, damaged, or have lost cells, these cells will renew the tissue that they populate.
There are different kinds of stem cells with different properties. The most primitive cells are the precursor cells that are uncommitted with very long telomeres which make them vibrant. Under precursor cells, you have the totipotent, pluripotent, multipotent germ layer stem cells. The totipotent forms everything that sends a conception this includes the embryo, placenta, sperm, and egg. The pluripotent can form everything except for the placenta and sperm. You may have heard of people talking about induced pluripotent stem cells, those are the cells that are able to form any cell of any tissue type. The multipotent germ layer stem cells are from the development of the embryo that has three layers which are the ectoderm, endoderm, and mesoderm. The multipotent germ layer stem cells eat within each derm layer and have multiple potentials to become a tissue of that layer.
As you go down their evolution pathway, you will find cells that are more committed which are the progenitor cells. Since they are more committed, they are won’t be able to become everything which the previous generation is capable of. These still have more potential than the previous generation, but as they divide they become less. From a tripotent to bipotent to unipotent, they just keep getting narrower in their ability to become certain types of cells.
The embryo or fertilized egg is our first stem cell and then it divides into four-cell stage. From there it becomes the morula and then becoming a blastocyst. In the blastocyst, you will find the inner cell mass and that is usually what people refer to as embryonic stem cells. They are taking one of these cells and expanding them, but this is just for research purposes and is not allowed for clinical use.
Totipotent stem cells have certain markers that help you identify that they are totipotent. As they differentiate more, their different markers will start to show up. That’s one way you can tell what kind of cells they are.
The blastocyst on the early stage is the epic blast like stem cells that are differentiated into three layers which are the ectodermal, endodermal, and mesodermal. Each layer will become these tissue-specific type stem cells which are the multipotent, tripotent, bipotent, and unipotent.
The ectoderm’s outer layer will become cells of the skin and nervous system neurons. The mesoderm becomes the spinal cord, skeletal, kidney, and blood. The endoderm becomes the pancreas, thyroid, and lung.
Blastomeres have pluripotent like potentials and have evidence that these may persist to adulthood. Although there hasn’t enough research done about blastomeres, if we can get the pluripotent stem cells and transplant those in our body, then that can be ideal.Endogenous stem cells are cells within our body that have different markers that show these are pluripotent stem cells. These are all different cells in the human body that have pluripotent potentials.
Classifications of stem cell therapies (6:52 – 8:40)
Autograft is when you derive from your own tissue and then you put it back in your own body. Allograft is from an allogenic source which means you get cells from one human to another. Xenograft is where you get cells from different species, and this is done in many countries especially in Southeast Asian countries.
Another division is the embryonic stem cells versus adult stem cells. Adult stem cells can be bone marrow-derived which has the longest history where the first case was in 1956. It can also be adipose-derived and was first discovered in 2001. Then there is the perinatal derived which is right around the time the baby is born it’s still considered as adult stem cells. This is because they are way more adult-like than embryonic stem cells and their properties are settled. They don’t have the potential that embryonic stem cells have to go haywire, generate teratomas, or have tumor formations. Even though perinatal derives are younger, they are still adults. They have already gone through the evolutionary pathway long enough that they will not go haywire.
Embryonic stem cell therapy (8:41 – 9:31)
Embryonic stem cell therapy is where you have the fertilized egg that becomes a blastocyst then gets cells from the inner cell mass. This is about five to seven days after the fertilization process. The culture that and induce the cells to become different cells of the tissue. However, the problem is there hasn’t been enough control of their destiny because there are still cases of people having tumor formations in different strange locations. For this reason, the U.S. has not given permission for it to be used clinically.
Bone Marrow Aspiration and Liposuction (9:33 – 13:31)
Bone marrow aspiration is usually at the hip or the iliac crest it’s a painful procedure. However, some doctors claim that they can do it with less pain, but it’s still quite a painful procedure. Then there is the liposuction where they get the cells from fat. When they get it from fat, they are actually getting it from the blood vessels in the fat. Fat is a very well vascularized type of tissue, as they spin it down they are mostly getting the MSC’s or Mesenchymal stem cells. As they hover around the blood vessel there are parasites, so as they spin it down they are also getting those parasites and those perivascular stem cells. Those are the cells they use for regeneration. Fat from different areas has different properties. Fat near your abdomen has more toxic build up, while fat on your right and left flank are better. There is limited supply and when you do liposuction, tissues will be expanded and it will have a lot of damage. You are causing significant injuries to those cells and then taking the stem cells out and re-infusing them. These stem cells have intelligence and they are attracted to areas with an injury. This means that most of the cells that you have re-infused will return to its original location. A lot of research has still shown good results from these MSC’s and perivascular stem cells.
Here are some statistics about MSCs in the body, when you are born 1 in 10,000 of your cells are MSC that is distributed throughout your body. There is a sharp decline in the number of these cells as you grow older. When you are in your teenage years it will drop down to 1 in 100,000. When you are in your 40s it will drop down to 1 in 400,000 and in your 80s it will drop down to 1 in 2 million. It’s not only the decline in their numbers but their ability to reproduce different factors, to be activated, and to start regeneration. That’s one concern with fat derives and the majority of doctors are using fat derives or bone marrow. Results are variable, sometimes it will work sometimes it doesn’t. Also the processing, you’re processing it your own clinic. You learn from a course you took and from the manufacturer, you are learning how to do it. That could introduce a lot of variabilities on what you are able to achieve.
Autologous Stem Cell Transplant (13:58 – 15:33)
The advantage of using your own cell is that it is a perfect match for yourself. If you put a stem cell in yourself in a particular tissue, then it’s possible that the stem cell can differentiate and become part of your tissue. There won’t be any signs of rejection and it will stay in your body longer.
This disadvantage of using your own cell is that it’s invasive and inconvenient that there’s risk of infection. With age or disease conditions the quality of the stem cell will decline. For example, the red marrow will start to change to yellow marrow as the person ages. The cell quantity is inconsistent when they perform the procedure and the stem cells are less potent with shorter telomeres, and fewer generations remaining. There are review studies that compare the MSC’s from the birth tissue versus from bone marrow and fat. They found that the MSC’s from the umbilical cord from the birth tissue, produced more anti-inflammatory factors, they are more robust, and they have newer protective functions. There are many parameters that show that these are superior in many ways.
Peri-natal Cell Sources (15:34 – 17:44)
In the perinatal cell sources, there is the fetal tissue of the placenta and the cord. The chorion is part of the mother, and the amnion is the baby’s tissue. When a baby is born you will hear about companies that have umbilical cords. They can work with the hospital and supposedly they can only accept placentas that are obtained through c-section. This is because that’s a completely sterile environment that hasn’t gone through the birth canal. They want this sterile organ that will go through all kinds of screening that’s the same level of screening as organ donation or blood transfusion. The placentas go through the same type of disease testing, checking the mother’s monitor, and the entire health history is taken. However, this is only done if the mother has agreed to donate the tissue. It also depends on the labs that need the tissue. Some may want low-quality product, while some may only take the highest quality. Not every baby is the same; a tiny mother with a normal weight baby can have the biggest cord, while a bigger person can have a long skinny cord.
Allogeneic Stem Cell Transplant (17:46 – 23:20)
The disadvantage of this procedure is that there is a potential immune response if you are giving tissues from one person to another. When cells are separated during the transplant, within the stem cells there are some surface markers or very small cells usually a few microns. These cells haven’t developed surface markers to mark them as a different individual. So when these cells are transplanted into another person, it will look like a blank cell to that person’s immune system. The problem happens when the cell tries to differentiate, that’s when they start to go down their pathway and express different markers which will then trigger the immune system.
In the past, a lot of scientists thought that the way stem cell works are by putting into somebody’s body and it will automatically become part of the injured tissue. But in the new science, there is lots evidence that shows the rate in which they repair is not by becoming your tissue, and not by replacing what’s damaged. It’s actually by first calming down the inflammation to create an environment of healing where the repair can occur. Then, it sends signals to active molecules to your immune systems so different cells can come in and help with the repair and stimulate local stem cells. Even people who got allogeneic stem cell transplants from another person to repair their tissue. Once they analyzed the tissue, it’s their own cells. These cells serve as a conductor in symphony to command other cells what to do in order to repair the tissue then eventually die.
“When I do stem cell transplants with for patients, I give them these cells. The cells will usually last in the body for about three to six months. Everyone is different but on average six months is how long they would last,” Said Dr. Joy Kong. Stem cells die just like other cells in the body, and these stem cells when they are freed from another source, where they have gone through a little bit of trauma. They come out of something else which makes it difficult for them to survive. But when they try to go to your inflamed sites and try to repair they are also experiencing a toxic environment.
Just like a soldier that’s going into battle and trying to fight back, they can get injured or even die. Cells have an attrition rate, and while they are combating inflammation injury they can also be sacrificed. That’s basically one reason why the cells drop in the number and die.
One of the advantages of this stem cell transplant is that they don’t engraft easily. There’s no matching necessary because they don’t have the surface markers and they are considered immune privileged. They have immunosuppressive properties which make them safe. During an organ transplant, they would also give them MSC’s to prevent organ rejection. “I have done a lot of these treatments for my patients, there are some patients that are curious and want to make sure that this is safe. So they will look everywhere for answers and will eventually give up and say they can’t find anything. This is because it is exceedingly safe,” said Dr. Joy Kong. The cells are primitive they are more potent, and they differentiate more efficiently with longer telomeres which makes them more robust. They may contain pluripotent stem cell populations with more embryonic characteristics. They are very easy to obtain with no ethical considerations because nobody is getting hurt.
Amniocentesis (23:22 – 23:44)
This process is where people get stem cell-like products from the amniotic fluid. During early pregnancy, the products are obtained between three to six months and these are the time where the product is more therapeutic.
Amniotic Fluid-Based Cell Therapy (23:46 – 25:36)
The advantage of this therapy is that there are a lot of growth factors which makes this very helpful. When people do wound healing or local tissue injection it does work due to its growth factors. The cells are very young usually three to four months and may have pluripotent stem cells.
The disadvantage is that there are a very limited number of cells. Amniotic fluid has very few cells that float around in it. The FDA even prohibits amniotic products to be called stem cell products. A lot of the amniotic fluid is obtained from people that are doing an amniocentesis. They do this because they want to know if there is anything wrong with the baby. People who are doing it have higher risks of having genetic defects. This is also invasive which means there is a risk of miscarriage. There is also an ethical consideration where some women will want to sell their amniotic fluid.
Human Umbilical cord (25:37 – 29:32)
There are two arteries in the umbilical cord and the rest are a gelatinous material called Wharton’s jelly. A lot of studies have been done on cells obtained from Wharton’s jelly because it’s very rich in MSC’s. MSC’s was discovered by Dr. Arnold Kaplan and was called mesenchymal stem cells which he regretted later. He then renamed it to medicinal signaling cells because he said that, “there is no evidence that these cells actually differentiate.” He believed that these cells are a master of regeneration. They have evidence of how these cells make contact with local stem cells and send signals to direct the direction on how they should act. They don’t actually send the signal but they are the controller of the regeneration. The tissue found in Wharton’s jelly is extremely rich in MSC’s and because it is only nine months old, it has lots of growth factors and many kinds of properties.
A study was done in Stanford on mice, where they infuse them with old people’s blood and a young person’s blood. The results showed that the mice that received the young person’s blood to regain some of their memory, liveliness, and go through their maze better. So they tried figuring out what was found in the younger person’s blood that the older didn’t have. They were able to find a protein called tip-to protein that’s rich when a person is first born. This protein will gradually decline as the person gets older.
The core blood is mostly hematopoietic stem cells and the core tissue is mostly mesenchymal stem cells these are very different types of stem cells. Overall they will give rise to all the cells in your circulatory system such as the white and red blood cells, and platelets. There are still different kinds of MSC’s supposedly they will give rise to all the other tissue but Dr. Kaplan thinks that they are more of the master.
Why are MSC’s Important? (29:34 – 33:24)
The paracrine effect is about the stem cells being in a local environment and sending signals to cells in the surrounding areas. They are telling all the other cells what to do and induce changes in nearby cells. The immunoregulatory is where the MSC’s are able to modify and regulate new functions which cause a shift from a highly inflammatory to an anti-inflammatory. The anti-inflammatory has many factors that create anti-inflammatory molecules. The anti-apoptotic helps rescue cells induced by trauma, hypoxia, or any other kind of damage. They also have antimicrobial properties and secrete antibodies. They have different peptides and are effective for chronic infections. This often used by Lyme disease patients, stem cells found in the umbilical cord has a qualitative difference and can definitely cure patients with Lyme disease.
Mesenchymal stem cells now renamed medicinal stem cells orchestrate the activities of local stem cells. They produce huge quantities of biomolecules and can be immunosuppressive. They are also able to put up a curtain of molecules around themselves that allow mesenchymal stem cells to be transplanted into the recipient without a new response. MSC’s also release these factors help reduce the immune response which hinders the body from rejecting certain cells.
Umbilical Cord MSC’s (33:25 – 35:35)
The umbilical cord derives stem cells that have a lot of MSC’s if you use cord tissue. The cord blood has 0.1 to 1 percent of mesenchymal stem cells. Most companies that sell perinatal stem cells products are using umbilical cord blood-derived because they are easy to separate. The cells are already in a suspension and if you spin it down, there won’t be much trauma to the cells which is why the product is easily made. Unfortunately, there is not that many mesenchymal stem cells there. The core tissue is gelatin-like that is wrapped around those cells that are embedded in the tissue. So how do you free those cells without using enzymes? There has to be a mechanical manipulation or cutting involved to separate the cells because the FDA doesn’t allow to be used.
Many scientists can do cord blood easily but have trouble with the cord tissue. Though it is still worth trying because the cord tissue is where the most valuable components are. MSC’s provide immune modulating capacities that stimulate regeneration. There is no need to collect the SAP cells through invasive procedures such as liposuction or bone marrow collection. The cord MSC’s are more efficient in their proliferation differentiation than other types of adult stem cells. The umbilical cord cells have been proven to be more potent.
Clinical Benefits (35:37 – 41:08)
These are some of the conditions where the stem cells have proven to be helpful. Autoimmune disorders, neurological conditions, type2 diabetes, heart disease, osteoarthritis, erectile dysfunction, dermatological conditions, lung conditions, injuries, autism, spinal cord injuries, and anti-aging. Here are some conditions that are treated by stem cells.
An 80-year-old patient joining a clock that’s completely it’s barely a clock, all the numbers are lined up in an abnormal way. A month after the stem cell treatment, the person got intranasal cells. When you put cells near the nasal area, it can be up taken to the brain and cross the blood-brain barrier. This is because the olfactory nerves have the ability to uptake them and bring them to the brain. That 80-year-old patient got the treatment and a month after the injection, the clock was vastly improved making a lot more sense. The numbers were spreading around the perimeter which actually made it look like a clock. Although it was still not a perfect clock, the intriguing thing is that there is nothing in medicine that can produce that kind of benefit.
For erectile dysfunction, people do notice a significant benefit when using stem cells.
A lot of people use PRP which has been around for a long time, however, the PRP’s effect will last about six months. The stem cells, on the other hand, will last a year or two. Stem cells are more potent products and have the intelligence to respond to your local environment. Instead of PRP just focusing on the growth factors, there is a limit on how much those growth factors can do compared to live cells.
A lot of kids go to Panama to get treatment for their autism. They would usually spend 20 to 30 thousand dollars to get the treatment. In Panama, it’s also umbilical cord stem cells but they expand it. They expand it into a hundred million to two hundred million cells and give that to patients, whereas our cells are only 15 to 20 million cells. When the patient came back after getting the treatment that uses umbilical cord stem cells, the kid responded much better these cells.
There are new researchers that show that expanded cells are less potent than native cells. Native cells mean that you have never manipulated it or never grown it. Expanded cells have been grown and cultured, they are incubated and they can grow into a lot of numbers. They’ve shown a graph that shows a hundred thousand native cells that gave a certain level of benefit, but expanded cells that were 10 times their number still proved to be less potent. That basically explains why we are using native cells because expanded cells are not allowed to be used in the U.S.
Studies have also shown that there are anti-aging properties. The study showed three months and six months results after IV infusion. The people’s skin, hair, energy levels, and libido have shown improvement.
Are these all intravenous administration? (41:10 – 42:38)
Not necessarily, but for a lot of the internal organs IV will be important. For patients with osteoarthritis or erectile dysfunction, for example, the injury is in a particular area so it will be better to inject cells right in the area because you get a huge concentration of growth factors. The IV is going to help improve your entire system even osteoarthritis the inflammation found through the body. This is why it’s always good to address your systemic health and even through small joints using an IV will be sufficient.
Modes of Delivery (42:39 – 44:00)
There is again the intravenous administration, interarticular, intramuscular, intrathecal, and intranasal. Interarticular is important when you have a large joint such as the hip, knee, and shoulders. This is important when you are certain that the problem is within the joint itself. It’s important to identify it properly because there are people with joint problems that are found in the surrounding tissue. In those with osteoarthritis when you look at the cartilage damage, the outer one-third is nourished by the blood supply. The inner two-thirds are nourished by the synovial fluid. So if you are doing IV, they may not address the internal environments as well. You should probably give a dose right into the joint space. Intranasal is a lot more comfortable, safer, and convenient. There are some people that prefer to inject directly into the organ of interest.
Dosing (44:01 – 47:03)
If you are going to do IV, then 0.5 million cells per kilo body weight will be sufficient. For example, a 62-kilo person will need 31 million cells so the product you should use should have 8 million cells per cc. They come in boxes and you can order them based on your needs which make it very convenient. It’s done in an FDA registered and inspected lab so you know they’ve gone through every safety procedure and quality control. Lots of patients come in for anti-aging purposes because these cells last in the body for about six months. However, if they have an aggressive disease process, then they may notice within three months that there is some relapse in symptoms. If they do everything right, getting the right nutrition, addressing their hormone issues, or they detox, then the stem cells will last a longer.
It’s important to always do a comprehensive evaluation because you are protecting an investment. Your physical body has all these parts and components that need to be addressed. There are patients that are regimented that come in every three to six months just so they know that they are helping their body regenerate, repair, and prevent the decline. When a person is really healthy they may not notice a lot of difference but that doesn’t necessarily mean that benefit is not there. Just like when we get sick, there are times when we don’t know that we’re getting sick and all of a sudden you are sick. But does that mean that you were not sick before? A lot of times you were sick but you haven’t hit the threshold that identifies that you are sick. This is the same thing when you are getting better. You may not know you are getting better but that doesn’t mean the repair isn’t happening.
Stem Cell IV Infusion Protocol (47:04 – 48:02)
You get the cells in a vial; you roll in your hand because you need rapid volume. If you do it too slowly there can be a certain temperature around -6 degrees where there is a potential for crystal formation. This can puncture the cell membrane and die, so you want to do very rapid volume on your hand then join the solution and put in the IV bag.
What does it mean for you as a Doctor? (48:14 – 50:06)
Basically, this is just to inform you that stem cells are very powerful tools for regeneration and can be used as therapy. It has a lot of advantages over traditional medical approaches because there are little side effects. When you use this you are kind of going back to your origin using what made us. The intelligence that was in the embryo is still in us and these are the stem cells. So, what can make us as a human from that one cell, that kind of intelligence is unimaginable. If we can use that instead of trying different types of chemicals to come up with something that can do everything, then that can be arrogance. To engage in nature’s innate intelligence is the future of where we should be going.
This eBook is based on Dr. Joy Kong’s Scottsdale 3/8/2018 Lecture on Current Stem Cell Therapy.