STEM CELL INFORMATION
1. What are Stem Cells
A stem cell is the main building block of the human body.
When they divide, they can make either any one of the 220 different cell types in the human body or they can reproduce themselves, i.e. having the capability of self-renewing.
Stem Cells, during the lifetime of a human being, are acting like “maintenance crews” helping a human body to maintain and restore its cellular structure and function as its neural network is directing stem cells to areas of disease, injury or inflammation.
Stem cells are the most important art of the Human biological system of about 100 Trillion cells, embedded in an electromagnetic energy field, communicating with its specific neural network, able to exchange and analyze information and with this, initiating impulses triggering biological, electrical and chemical-related reaction at its cellular basis. (N1)
This natural regenerative capability can be influenced in various ways involving stem cells. Today we can divide stem cells into basically four main kinds of cells:
1. Embryonic Stem Cells
2. Adult Stem Cells
3. Induced Pluripotent Stem Cells (iPSC)
4. Gene manipulated cells
The first two (Embryonic and Adult Stem Cells) are part of the natural development of beings, whereas the group 3 and 4 (iPSC and Gene manipulated cells) are men made, artificially developed and highly manipulated cells.
While Embryonic Stem Cells are responsible to build the human body from the fertilized egg, until a baby is born, Adult Stem Cells develop from embryonic stem cells, then become fetal stem cells and with the birth mature into adult stem cells. Those adult stem cells are the reserve supply of cells that can multiply when needed to repair, regenerate damaged organs and tissues. Adult stem cells are readily available for personalized autologous medical treatments as they can be harvested easily and returned without heavy manipulation back to the same individual to help a body to restore itself.
When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.
Stem cells are distinguished from other cell types by two important characteristics. First, they are unspecialized cells capable of renewing themselves through cell division, sometimes after long periods of inactivity. Second, under certain physiologic or experimental conditions, they can be induced to become tissue- or organ-specific cells with special functions. In some organs, such as the gut and bone marrow, stem cells regularly divide to repair and replace worn out or damaged tissues. In other organs, however, such as the pancreas and the heart, stem cells only divide under special conditions. (N2)
In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells e.g. skin cells to be “reprogrammed” genetically to assume a stem cell-like state. This new type of adult-derived stem cell, called “induced pluripotent stem cells (iPSCs)”.
iPSCs are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells. Although these cells meet the defining criteria for pluripotent stem cells, it is not (yet) known if iPSCs and embryonic stem cells differ in clinically significant ways. Mouse iPSCs were first reported in 2006, and human iPSCs were first reported in late 2007. Mouse iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cells from all three germ layers, and being able to contribute to many different tissues when injected into mouse embryos at a very early stage in development. Those stem cells are experimental and genetically modified and became a new field of stem cell research, and it remains to be seen whether they do not develop unwanted side effects due to their strongly manipulated and modified structure. Genetically manipulated cells are going even one step further and will have to follow the clinical trial route before approved for human treatments. (N2)
2. Potency of Stem Cells (N1)
The main difference between embryonic stem cells and adult stem cells is the type of potency. Potency of the stem cell specifies the differentiation potential i.e., the potential to differentiate (develop) into other cell types. The following summarizes the “potency of stem cells”:
are stem cells that can differentiate into embryonic and extra embryonic cell types. Such cells can construct a complete, viable organism. These cells are produced from the fusion of an egg and sperm cell. The only totipotent cells are the fertilized egg and the cells produced by the first few divisions of the fertilized egg are also totipotent. Totipotent stem cells give rise to somatic stem/progenitor cells and primitive germline stem cells.
are stem cells that are the descendants of totipotent cells and can differentiate into nearly all cells, i.e. cells derived from any of the three germ layers.
These pluripotent cells are characterized by self-renewal and a differentiation potential for all cell types of the adult organism. These are true stem cells, with the potential to make any differentiated cell in the body. Embryonic Stem Cells come under this category, as well as recently discovered “induced Pluripotent stem cells (iPSC) where adult cells are reprogrammed to have embryonic-like features.
are stem cells that can differentiate into a number of cells, but only those of a closely related family of cells. These are true stem cells but can only differentiate into a limited number of types. For example, the bone marrow contains multipotent stem cells that give rise to all the cells of the blood but not to other types of cells. Adult Haematopoietic Stem Cells are multipotent. Adipose tissue is a rich source of multipotent stem cells. Multipotent stem cells form multiple blood cell lineages.
are stem cells that can differentiate into only a few cells, such as lymphoid or myeloid stem cells. The corneal epithelium is a squamous epithelium that is constantly renewing and is Oligopotent.
are cells that can produce only one cell type, their own, but have the property of self-renewal, which distinguishes them from non-stem cells. Such Unipotent cells include muscle stem cells. Most epithelial tissues self-renew throughout adult life due to the presence of unipotent progenitor cells.
3. Adult Stem Cells
As mentioned before, Adult Stem Cells develop from embryonic stem cells, then become fetal stem cells and with the birth mature into adult stem cells.
Adult stem cells can be extracted from many areas of the body, including the bone marrow, fat, and peripheral blood. Once the cells have been harvested, they are either processed at the bed-side, where they are purified and assessed for quality before being reintroduced back into the patient, or sent to a lab for expansion before being reintroduced back to the patient.
Since this type of stem cells come from the same patient there is no possibility of rejection. Adult Stem Cells also called Somatic Stem Cells exist naturally in the body. They are important for growth, healing, and replacing cells that are lost through daily wear and tear.
Those adult stem cells are the reserve supply of cells that can multiply when needed to repair, regenerate damaged organs and tissues. We can visualize this repair and regeneration capability of stem cells by using a “Pharmacy as a model”. What does this mean?
A Pharmacy, on day one, is fully stocked with medicaments to dispense those medicaments to patients in need. In our model “day one” equals the birth of the baby fully loaded with all kind of cells, stem cells and growth factors for future repair needs of the body. While the baby is growing, the body, or in our pharmacy model, the patients, are using up the stock of the pharmacy. In a real pharmacy, the supplier of medicaments always replaces what had been taken by patients. This capability to replenish the depot is limited when it comes to our cell structure in our body, although stem cells have the capability to renew themselves, i.e. make copies.
The scientist believes that illness and aging is a result of the incapacity of a human body to regenerate over time fully those used and dying cells as the “depot in our body” is either exhausted or damaged.
On average each of us replaces, i.e. regenerates about 1.7 to 2.5 Million Cells per second, from the about 80 to 100 plus trillion cells any human has. We are not really aware of the cellular activities in our body, but it is happening all the time. We also need to understand that the rate of red blood cell production slows as we grow older. The reason for this is each cell has chromosomes, which contain our DNA. At the end of our chromosomes, we have “caps” called telomeres. As our cells divide, these telomeres begin to shrink. Each time the cell divides the telomere gets shorter, the chromosomes are less protected and finally, the chromosomes are exposed to damage, and cell division stops. So, cell division slows as we age. Furthermore, when younger, we are growing and so our body not only has to replace dying cells but make new cells for growth. When humans reach adulthood, our body ceases growth.
As a simple example, when we cut our finger accidentally with paper, it hurts, the cells around the injury, the cut, signals to the cellular system we have a problem, and with this signal we are initiating the message to the various cell types “fix it”!
Millions of cells are mobilized to close the wound and heal the cut….a process which is happing automatically! With age, we have fewer stem cells and growth factors and the capability to heal our body slows down eventually.
Research has, however, shown that by harvesting stem cells from e.g. bone marrow or adipose tissue (fat) and returning it back to the same body has the capacity to “increase the reserve” in our body and helps the natural capability to increase healing of various illnesses due to the so-called “homing capability” of stem cells, meaning they are automatically, after re-injected into the body, travel to those places (wounds) where needed.
Where can we find adult stem cells?
Adult stem cells have been identified in many organs and tissues, including the brain. Bone marrow, peripheral blood, blood vessels, fat tissues, skeletal muscle, skin, teeth, nose, heart, gut, liver, ovarian epithelium, and testis to name a few of the 220 different cells in the human body. They are thought to reside in a specific area of each tissue, called a “stem cell niche”.
The primary function of adult (somatic) stem cells is to maintain tissue homeostasis by replenishing senescent (growing old) or damaged cells. Homeostasis can be defined as a property of an organism that helps it maintain its parameters within a normal range of values. It is key to life, and failures in homeostasis can lead to diseases like hypertension and diabetes.
Regenerative medicine is using stem cells from umbilical cord blood, bone marrow, peripheral blood and more recently from adipose tissues. The advantage of adipose tissue is that, as recent research confirmed, that there are 500 times more mesenchymal stem cells in 1 gram of fat than there are in 1 gram of bone marrow. The advantage is that without expanding them a physician can harvest a small quantity which already has a therapeutic value. New technology to extract bone marrow has recently evolved and has increased the number of harvested stem cells from bone marrow considerably.
4. Stem Cells and Regeneration
Scientist and regulators are defining stem cells also into the following four main categories when it comes to transplanting them:
Allogeneic Stem Cells, the cells come from an unrelated donor.
Autologous Stem Cells, the cell comes from you.
Syngeneic Stem Cells, the cells come from your identical twin or triplet.
Xenogenic Stem Cells, from animals, also call life cell therapy
Regeneration is probably the most important possible medical application of stem cells in the 21st-century medical advancements. Currently, organs must be donated, harvested and transplanted, but the demand for organs far exceeds supply.
The allogeneic stem cell treatment method follows the pharmaceutical business model, with clinical trials in respect of safety and efficacy, which will take many years, and millions of dollars to develop a “nearly side-effect free” medical product. Those medical products, considered as “stem cells in a bottle” for use like a pharmaceutical drug will not take only years to develop due to the high potential of unwanted side effects like teratomas (cancerogenic) developments, but also will become extremely expensive to those having to pay for the treatment.(N1)
Autologous stem cells as an alternative can be easily harvested from the own body.
The main source had been bone marrow and more recently adipose tissue (fat). The advantage of autologous Stem cells in comparison with Allogeneic Stem Cells is that there is no need of immune-depressants and the risk of infection is next to non-existent as you use your own cell structure. Furthermore, they can be harvested quickly and easily via a mini-liposuction, purified and redeployed to the same body at the same day surgical procedure which takes between 3 and 4 hours at a qualified clinic. Furthermore, the costs of this kind of medical treatment are much less than those treatments with patented products, although the medical effect for a patient appears to be the same or similar.(N1)
The same can be said about stem cells from bone marrow.
Scientific reviews and applied autologous stem cell treatments, not only in the cosmetic field, but also in clinics using stem cells in the legal frame of “Practice of Medicine”, have shown that stem cell treatments with autologous stem cells can be considered as safe.
Stem cells isolated from the bone marrow or fat have the ability to become different cell types (i.e. nerve cells, liver cells, heart cells, and cartilage cells). Studies have also shown that these are capable of homing to and repairing damaged tissue. Animal studies have shown that these stem cells also secrete proteins and peptides that stimulate healing of damaged tissue, including heart muscle and spinal cord.
There are many scientific reviews on the safety of adipose-derived mesenchymal stem cells, confirming the safety of using MCS. One of them can be found at the following link.
In companion animals and horses with bone and joint injuries, stem cells from Bone Marrow and Fat have been used for the last five years with excellent results.
Experimental studies suggest that stem cells from adipose tissue and bone marrow potentially can develop into new tissues and also may suppress pathological immune responses as seen in autoimmune diseases.
Besides to use of stem cells for orthopedic conditions, various international clinics are treating patients with Rheumatoid Arthritis, Osteoarthritis, Multiple Sclerosis, and other autoimmune diseases using fat-derived stem cells.
5. Mesenchymal Stem Cells (N1)
Mesenchymal Stem Cells (MSC) are a specific type of stem cells described by Arnold Caplan, a scientist who coined the term “Mesenchymal Stem Cells” in 1991 for the type of bone marrow cells, previously known as “stromal stem cells”. This term became widely adopted. MSCs can be found in many parts of the human body like in umbilical cord blood, adipose tissue (fat), bone marrow, muscle or even the pulp of baby teeth.
Caplan views MSCs as a “drug-stores”, which can produce 10-20 biologically active substances. He thinks that FDA standards should not be applied to “live drug-stores”. He said: “We can’t use Pharmaceutical drug logic in regenerative medicine”.
Furthermore, he, in recent reviews (2012) mentioned that his new research indicates that MSC are rather progeny of pericytes, not real stem cells – the cells, attached to blood vessel’s wall in all tissues and organs. He, therefore, proposed to use for “MSC” an alternative term, i.e. “Medicinal Signalling Cells” instead of “Mesenchymal Stem Cells”.
So, to be entirely correct, mesenchymal stem cells (MSCs) are not stem cells. They are perivascular cells with highly significant paracrine activity. Additionally, they have keen sensory capabilities, allowing them to assay their surrounding microenvironment, to which they respond accordingly.
In one study, conducted at Case Western Reserve University, it was found that when MSCs are introduced into injured tissue, the injured tissue which is immediately next to the MSCs begins making 90 different transcripts. In other words, the therapeutic proteins which heal the injured tissue originate from the injured tissue itself, not from the MSCs. The new, healthy tissue which is formed, is formed from the host tissue, not from the donor cells (the MSCs). It is the MSCs, though, the donor cells, which trigger the host tissue to produce the therapeutic proteins which heal the tissue. Without the MSCs, the host tissue would not be stimulated into action to heal the injury.
The importance of this phenomenon cannot be overemphasized. It represents a major shift in the fundamental understanding of how these cells work.
In the late 1980s, Dr. Arnold Caplan of Case Western Reserve University was the first person ever to isolate MSCs, from bone marrow, and expand them in culture. He is the one who named them “mesenchymal stem cells,” which, he now points out, is the wrong name. In his testimony before the FDA/CBER (Food and Drug Administration / Center for Biologics Evaluation and Research) in September of 2016, Dr. Caplan stated:
“In the late 1980s, I gave the term “Mesenchymal Stem Cells” to a cell which I was able to isolate from bone marrow, put into culture and expand in culture. That term is wrong, and I apologize for calling it a stem cell. It is not a stem cell. The assumption was that this cell was part of the stroma of marrow. This cell is not a part of the connective tissue or stroma of marrow, it is a perivascular cell, and as a perivascular cell it has a function only in cases of inflammation or injury. In this case, this cell comes off the blood vessel and does two things: from its front, it secretes a curtain of molecules which stop your overaggressive immune system from surveying the damaged tissue behind it. And from the back of the cell, it secretes a different group of factors which actually allow the tissue behind it to regenerate in a slow and unscarring process. This, therefore, is a cell which is medicinal in its function. And because I have such a delicate ego, I have written an article which asks my colleagues to continue to use the MSC nomenclature, but I’ve renamed this cell a “Medicinal Signaling Cell.” So therefore, when I lecture, I beg the audience to not use the stem cell nomenclature.”
Independently of this discussion of alternative terms and the understanding of what are MSCs, the fact is, that MSC are valuable sources for regenerative medicine and science since 2014 it has not changed its term, i.e. referring to “MSC still as Mesenchymal Stem Cells”.
MSC, today (2018) are referred to as multipotent stem cells because they can develop into multiple tissues, but they apparently do not have the capacity to reconstitute an entire organ. The newly developed 3D bio-printing technology may, however, use MCS as the raw material source to print fully functioning organs.
Recent research (2012) showed, that an extremely rich source of mesenchymal stem cells can be found in developing tooth bud of the mandibular (lower) third molar, or wisdom tooth. While considered multipotent, these stem cells, in the end, may prove to be pluripotent, capable of generating all tissue types. The stem cells found in developing third molars eventually form enamel, dentin, blood vessels, dental pulp, nervous tissue and a minimum of 29 different unique tissues and organs. Because of extreme ease in the collection at 8–10 years of age, they will probably constitute a major source for personal banking, research and multiple therapies in future.
Most interesting at the time of writing (April 2015 / update 2018) are, however, MCS from adipose tissue (fat). Recent scientific research suggests that there are 500 times more mesenchymal stem cells in 1 gram of fat than there are in 1 gram of bone marrow, which would make it easier to use therapeutical without expanding the cells. New bone marrow harvesting technologies claim that they may compensate for this.
Mesenchymal stem cells are of intense therapeutic interest because they represent a population of cells with the potential to treat a wide range of acute and degenerative diseases. Stromal Vascular Fraction (SVF) from adipose tissue (fat) and bone marrow is a rich source of MCS and already widely used for experimental patient funded studies in many qualified clinics around the world with interesting positive results.
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(N1) CellularStem – The Science of Regeneration, Sister company of ARISTOLOFT