Definition of a Stem Cell
“Stem cells are a special type of cells that have two important properties. They are able to make more cells like themselves. That is, they self-renew. And they can become other cells that do different things in a process known as differentiation. Stem cells are found in almost all tissues of the body. And they are needed for the maintenance of tissue as well as for repair after injury." (1) - MayoClinic.org
There are many types of stem cells. Embryonic (ESCs), Induced Pluripotent (iPSCs), Hematopoetic (HSCs) and Mesenchymal (MCSs).
When you compare the different sources of stem cells, perinatal tissues clearly have the advantage over other sources at this time.
In the future, iPSCs will be the premier stem cell source but today if you want to get a stem cell treatment the best source is from perinatal tissues and in particular the UC-MSC from the umbilical cord and placental tissue is the #1 regenerative medicine cell.
“Stem cells are a special type of cells that have two important properties. They are able to make more cells like themselves. That is, they self-renew. And they can become other cells that do different things in a process known as differentiation. Stem cells are found in almost all tissues of the body. And they are needed for the maintenance of tissue as well as for repair after injury." (1) - MayoClinic.org
There are many types of stem cells. Embryonic (ESCs), Induced Pluripotent (iPSCs), Hematopoetic (HSCs) and Mesenchymal (MCSs).
When you compare the different sources of stem cells, perinatal tissues clearly have the advantage over other sources at this time.
In the future, iPSCs will be the premier stem cell source but today if you want to get a stem cell treatment the best source is from perinatal tissues and in particular the UC-MSC from the umbilical cord and placental tissue is the #1 regenerative medicine cell.
Mesenchymal Stem Cells
Mesenchymal Stem Cells (MSCs) are found in bone marrow and in the perinatal tissues like the placenta and the wharton's jelly/umbilical cord (UC-MSCs). MSCs are the ideal cell for regenerative medicine treatments. MSCs can form all three germ layers meaning that from MSCs can form bone, cartilage, muscle tissue, nerve tissue and organs.
An MSCs was first defined by the International Society Cell and Gene therapy (ISCT). (2)
“First, MSC must be plastic-adherent when maintained in standard culture conditions.
Second, MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79α or CD19 and HLA-DR surface molecules.
Third, MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro.”
MSCs have low expression of MHC Class II molecules and lack co-stimulatory molecules like CD80, CD86, and CD40, making them less likely to trigger immune responses.
They are often described as "immune privileged." Immune priviledged means that MSCs do not need to “match” the donor and the recipient in the same manner that HSCs need to match making MSCs the ideal universal cell for regenerative medicine.
Advantages of Umbilical Cord MSCs (UC-MSCs)
Although bone marrow and adipose tissue (fat) contain MSCs, the MSCs from perinatal sources and particularly from from the Wharton’s Jelly of the Umbilical cord tissue are superior sources of MSCs.
MSCs by definition express the markers CD105, CD73 and CD90.
However, MSCs from the umbilical cord also express Oct-4, Sox-2 and Nanog.
Oct-4, Sox-2 and Nanog are markers that are known as embryonic stem cell markers and have to do with greater telomerase potential.
Telomerase control the stem cell’s ability to make perfect copies of itself which is also known as population doublings without senescing or dying.
Oct-4, Sox-2 and Nanog markers are considered Pluripotent ESCs markers and are not expressed on adult MSCs from bone marrow and adipose.
The expression of these ESCs markers make perinatal derived MSCs more proliferative with greater therapeutic potency than MSCs from adult sources (bone marrow and adipose tissue).
Of all the MSCs sources the most widely studied and the ideal stem cell for regenerative medicine treatments is the Umbilical Cord derived MSC or UC-MSCs.
Mesenchymal Stem Cells (MSCs) are found in bone marrow and in the perinatal tissues like the placenta and the wharton's jelly/umbilical cord (UC-MSCs). MSCs are the ideal cell for regenerative medicine treatments. MSCs can form all three germ layers meaning that from MSCs can form bone, cartilage, muscle tissue, nerve tissue and organs.
An MSCs was first defined by the International Society Cell and Gene therapy (ISCT). (2)
“First, MSC must be plastic-adherent when maintained in standard culture conditions.
Second, MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79α or CD19 and HLA-DR surface molecules.
Third, MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro.”
MSCs have low expression of MHC Class II molecules and lack co-stimulatory molecules like CD80, CD86, and CD40, making them less likely to trigger immune responses.
They are often described as "immune privileged." Immune priviledged means that MSCs do not need to “match” the donor and the recipient in the same manner that HSCs need to match making MSCs the ideal universal cell for regenerative medicine.
Advantages of Umbilical Cord MSCs (UC-MSCs)
Although bone marrow and adipose tissue (fat) contain MSCs, the MSCs from perinatal sources and particularly from from the Wharton’s Jelly of the Umbilical cord tissue are superior sources of MSCs.
MSCs by definition express the markers CD105, CD73 and CD90.
However, MSCs from the umbilical cord also express Oct-4, Sox-2 and Nanog.
Oct-4, Sox-2 and Nanog are markers that are known as embryonic stem cell markers and have to do with greater telomerase potential.
Telomerase control the stem cell’s ability to make perfect copies of itself which is also known as population doublings without senescing or dying.
Oct-4, Sox-2 and Nanog markers are considered Pluripotent ESCs markers and are not expressed on adult MSCs from bone marrow and adipose.
The expression of these ESCs markers make perinatal derived MSCs more proliferative with greater therapeutic potency than MSCs from adult sources (bone marrow and adipose tissue).
Of all the MSCs sources the most widely studied and the ideal stem cell for regenerative medicine treatments is the Umbilical Cord derived MSC or UC-MSCs.
"During early embryogenesis, blood islands are first found in the yolk sac and later in the aorto-gonado-mesonephros (AGM) region. They then migrate through the early umbilical cord to the placenta. There is a second migration from the placenta again through the early umbilical cord to the fetal liver where blood islands are found and then finally to the fetal bone marrow where the hematopoietic stem cells (HSCs) reside. Included in these blood islands are early precursors of HSCs, as well as primitive mesenchymal- like stromal cells. These migrations take place between day 4 and day 12 of embryological development. Researchers have postulated that during this migration to and from the placenta through the umbilical cord, these mesenchymal-like stromal stem cells become embedded in the Wharton's jelly at a very early embryological age. (3)
It is believed by many that the formation of these cells at such an early embryonic state allows them to retain a resemblance to embryonic stem cells (ESCs), while still maintaining the properties of somatic mesenchymal stem cells found in bone marrow (BM-MSCs), as defined by the International Society for Cellular Therapy (ISCT) (2). As such, these umbilical cord mesenchymal stem cells (UC-MSCs) are in reality cells that fall somewhere between ISCT definitions of ESCs, mesenchymal stem cells and stromal cells. (4)."
Hematopietic Stem Cells
.Umbilical cord blood and placenta blood are rich sources of hematopoietic stem cells.
Dr. Hal Broxmeyer a pioneer in the stem cell world first discovered umbilical cord blood as a source of HSCs. The first hematopoietic stem cell transplant from cord blood took place in 1989 in France.
Hematopoietic cells require strict matching requirements for a safe transplant. Human leukocyte antigens (HLA) are proteins found on the surface of most cells in the body that help the immune system identify foreign substances. For a hematopoietic stem cell transplant you need to match HLA markers in order for the body to not reject the transplanted cells.
Embryonic Stem Cells (ESC)
The Embryonic Stem Cell (ESC) is the master of all stem cells. This cell is a Pluripotent stem cell meaning it can form any and all types of cells in the body. This is the cell that is produced by the joining of a sperm cell and an egg.
Embryonic stem cells were discovered at the University of Wisconsin in the lab or Jamie Thompson.
The embryonic stem cell also is the stem cell that is surrounded in controversy. Embryonic stem cells are harvested from a 200-cell blastocyst. This blastocyst is a collection of undifferentiated cells but when you collect these cells you stop the development process that would eventually form a human being.
Although it is not yet a human being at this point, it's a collection of 200 cells. If you believe that the soul is transferred at conception, then you believe that you would be killing a soul to harvest embryonic stem cells. And that is the ethical controversy surrounding embryonic stem cells and the George Bush Stem Cell Era of the early 2000s.
For our purposes today reviewing stem cells for the potential use to cure disease and illness in our lifetime, it is important to note that the George Bush ban on ESCs was only on labs that received government funding in the form of NIH grants. The ban was never applied to private companies which had full authority to experiment on ESCs.
If ESCs are the magical stem cell then what happened to the progress?
What happened was that as researchers experimented with ESCs they quickly learned that since the ESC is a pluripotent stem cell that can truly become any cell including cancer stem cells that form tumors. When the cell is manipulated in the lab to become other cell types it does just that and produces teratomas.
The pluripotency power of the embryonic stem cell makes it very difficult to control this cell in an artificial lab environment. The uterus is the greatest bioreactor in the world. When you manipulate these cells outside of the uterus or outside of the natural human birth process, these cells are so primitive and have so much potential that they quickly spin out control and result in the formation of tumors. And that is why we have not seen the advancement of embryonic stem cells, not because of lack of access, because of the inherent tumorgenicity of ESCs.
More resources on ESCs
Professor Jamie Thompson's paper on this discovery. (PDF)
MIT Review of ESCs.
ESCs Youtube video
.Umbilical cord blood and placenta blood are rich sources of hematopoietic stem cells.
Dr. Hal Broxmeyer a pioneer in the stem cell world first discovered umbilical cord blood as a source of HSCs. The first hematopoietic stem cell transplant from cord blood took place in 1989 in France.
Hematopoietic cells require strict matching requirements for a safe transplant. Human leukocyte antigens (HLA) are proteins found on the surface of most cells in the body that help the immune system identify foreign substances. For a hematopoietic stem cell transplant you need to match HLA markers in order for the body to not reject the transplanted cells.
Embryonic Stem Cells (ESC)
The Embryonic Stem Cell (ESC) is the master of all stem cells. This cell is a Pluripotent stem cell meaning it can form any and all types of cells in the body. This is the cell that is produced by the joining of a sperm cell and an egg.
Embryonic stem cells were discovered at the University of Wisconsin in the lab or Jamie Thompson.
The embryonic stem cell also is the stem cell that is surrounded in controversy. Embryonic stem cells are harvested from a 200-cell blastocyst. This blastocyst is a collection of undifferentiated cells but when you collect these cells you stop the development process that would eventually form a human being.
Although it is not yet a human being at this point, it's a collection of 200 cells. If you believe that the soul is transferred at conception, then you believe that you would be killing a soul to harvest embryonic stem cells. And that is the ethical controversy surrounding embryonic stem cells and the George Bush Stem Cell Era of the early 2000s.
For our purposes today reviewing stem cells for the potential use to cure disease and illness in our lifetime, it is important to note that the George Bush ban on ESCs was only on labs that received government funding in the form of NIH grants. The ban was never applied to private companies which had full authority to experiment on ESCs.
If ESCs are the magical stem cell then what happened to the progress?
What happened was that as researchers experimented with ESCs they quickly learned that since the ESC is a pluripotent stem cell that can truly become any cell including cancer stem cells that form tumors. When the cell is manipulated in the lab to become other cell types it does just that and produces teratomas.
The pluripotency power of the embryonic stem cell makes it very difficult to control this cell in an artificial lab environment. The uterus is the greatest bioreactor in the world. When you manipulate these cells outside of the uterus or outside of the natural human birth process, these cells are so primitive and have so much potential that they quickly spin out control and result in the formation of tumors. And that is why we have not seen the advancement of embryonic stem cells, not because of lack of access, because of the inherent tumorgenicity of ESCs.
More resources on ESCs
Professor Jamie Thompson's paper on this discovery. (PDF)
MIT Review of ESCs.
ESCs Youtube video
Induced Pluripotent Stem Cells (iPSCs)
iPSCs were discovered by Professor Shinya Yamanaka and for this landmark achievement he was awarded the 2012 Nobel Price in Medicine.
Professor Yamanaka became a hero in Japan and Japanese government embraced advanced regenerative medicine seeking to be the worldwide leader in stem cell science and research. Japan has succeeded in their goal due to their advanced regulatory framework. (*It is the Japanese regulatory framework that the Perinatal society advocates to be adopted in the US.)
Yamanaka’s Paper
Like ESCs, iPSCs are pluripotent. To harvest iPSCs you start with an individual’s skin cell and by introducing 4 reprogramming factors (c-Myc, Klf4, Oct3/4, and Sox2) to the skin cell you are able to reverse the cells development all the way back to a totipotent state. (Oct3/4, and Sox2 are expressed by umbilical cord.)
The implications for this technology simply cannot be overstated.
For example: A patient needs a new heart. The patient can donate her own skin cell which can then be induced back to a totipotent state and then directed to develop into heart tissue and ultimately a new heart that is 100% identical to the patient’s original heart because it came from the same DNA.
There are a number of different techniques to induce the cell to reverse back to the pluripotent state and this Nature paper does a good job of describing them if you would like to go deeper down this pathway.
However, much like ESCs, iPSCs have also shown to be tumorigenic.
The first clinical trials with induced pluripotent stem cells were stopped because the cells were unstable and formed tumors.
Since those first clinical trials a few more trials have started up again.
This link is a review of the trials past and current.
Jamie Thompson who was credited with the discovery of ESCs also was studying iPSCs and announced the discovery of iPSCs on the same day as Yamanaka.
Although the Nobel prize and fame went to Yamanaka, Jamie Thompson also is credited with this discovery within the scientific community.
I was very fortunate that my professional path enabled me to attend the 2008 World Stem Cell Summit at the University of Wisconsin. At the time of this meeting, iPSCs were the rage as the two papers mentioned came out the previous year.
Jamie Thompson gave the key note at the conference and stated that he believed that iPSCs were an amazing tool to study the interactions of the human cell but that therapies from this technology were 25 to 50 years away. This was a pretty huge statement from one of the scientists who discovered this technology.
Additional iPSC resource: A paper by Yamanaka titled “Induced Pluripotent Stem Cells: Past, Present, and Future” from 2012.
Throughout the 14 years of its existence, the International Perinatal Stem Cell Society has focused on working with industry and regulators to bring the field of Perinatal Stem Cells and Tissue regenerative medicine products to patients. We are now bringing stem cell therapies to Veterans and First Responders.
References:
1. https://www.mayoclinic.org/tests-procedures/bone-marrow-transplant/in-depth/stem-cells/art-20048117
2. https://www.isct-cytotherapy.org/article/S1465-3249(06)70881-7/abstract
3. Wang X-Y, Lan Y, He W-Y, Zhang L, Yao H-Y, Hou C-M, et al. Identification of mesenchymal stem cells in aorta-gonad-mesonephros and yolk sac of human embryos. Blood 2008;111(4):2436e43.
4. www.sciencedirect.com/science/article/abs/pii/S0143400411002189?via%3Dihub
1. https://www.mayoclinic.org/tests-procedures/bone-marrow-transplant/in-depth/stem-cells/art-20048117
2. https://www.isct-cytotherapy.org/article/S1465-3249(06)70881-7/abstract
3. Wang X-Y, Lan Y, He W-Y, Zhang L, Yao H-Y, Hou C-M, et al. Identification of mesenchymal stem cells in aorta-gonad-mesonephros and yolk sac of human embryos. Blood 2008;111(4):2436e43.
4. www.sciencedirect.com/science/article/abs/pii/S0143400411002189?via%3Dihub
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