Who needs stem cell therapies?

[Wise Young]

Several people have written to me asking whether they need stem cell therapies. Let me try to answer this question as best as I can here because I am sure that the question has occurred to many people.

First, before we go ahead, let me make sure that everybody understands the definition of a stem cell because it is not clear to me that most people are using the words correctly. A stem cell is a cell that can produce many kinds of cells (as well as itself). An olfactory ensheathing glial cell is not a stem cell because it can only produce other olfactory ensheathing glia. It does not produce neurons or astrocytes. Likewise, a Schwann cell is not a stem cell because it cannot produce many kinds of cells. An oligodendroglial cell is not a stem cell. An astrocyte is not a stem cell. In fact, many of these cells cannot produce even themselves. For example, a mature neuron cannot produce another neuron. Another kind of cell is necessary to produce a neuron: a neural progenitor cell. Note that some neural progenitor cells can produce astrocytes, oligodendroglia, and neurons while others can only produce neurons. Neural progenitor cells that produce only neurons are called neuron-restricted progenitors (NRPs). Neural progenitor cells that produce only glia are called glia-restricted progenitors (GRPs).

Bone marrow and umbilical cord blood contains cells called "mesenchymal stem cells" that can produce many kinds of cells but only under very special circumstances. In fact, if you transplant mesenchymal stem cells into injured adult spinal cord, the cells usually do not produce neurons or any other kind of cell. If it does make cells, it makes more of itself. This is because the adult spinal cord does not contain the factors that are necessary to stimulate the mesenchymal stem cell to produce other kinds of cells.

On the other hand, several groups have reported the mesenchymal stem cells will stimulate remyelination and, in some circumstances, may themselves help remyelinate axons. Because there is no definitive marker for mesenchymal stem cells, it is hard to get a pure culture of such cells from bone marrow, umbilical cord blood, or peripheral blood. One is usually transplanting a mixture of cells that include some mesenchymal stem cells.

In contrast, embryonic stem cells (obtained from blastocysts which are at the earliest stage of development) or fetal stem cells (obtained from fetuses) tend to produce neurons, astrocytes, and oligodendroglia when transplanted into the injured adult spinal cords. Embryonic stem cells are more unpredictable in that if they are transplanted in large numbers of the spinal cord, they may be fooled into thinking that they are in an embryo and therefore may produce all sorts of cells, including hair, skin, gut, and other cells. Such a growth is called a teratoma, a tumor of embryonic stem cells. Most such tumors are not very malignant and are typically relatively slow growing.

It is possible to pre-differentiate embryonic stem cells into neural progenitor cells by exposing them to a chemical called retinoic acid (RA). If they are exposed further to sonic hedghog (SHH), a factor that is known to stimulate neural stem cells to produce neurons, the cells tend to produce more neurons. But, all these manipulations are still relatively crude and better methods need to be developed.

OK, enough lecturing and let me try to answer the question. If you have flaccid muscle that cannot be stimulated electrically, this suggests that you have damaged the motoneurons that control the muscle. If the muscle can be activated electrically but you have no reflexes and no spasticity in the muscle, it suggests that you may have damaged some of the neurons that are responsible for the reflex. The segments where loss of neurons is most crucial are C3-5 and T10-L1 where the cervical and lumbosacral enlargements are present. Please note that flaccidity or loss of reflexes may also result from too much antispasticity drug or peripheral nerve injury.

A majority of people who have lower cervical and thoracic injuries would benefit regenerative therapies to get their axons to regrow and reconnect. But, if the neurons have been damaged, regeneration may produce only limited return. If you do have to replace or repair local neuronal circuits, stem cell therapies to replace neurons should be helpful.

Wise.

[anty]

Ok dr. wise in my case with TM what would be good for me you saw my mris. I am waiting for a bike for my house to build up some more muscle in my legs and try to lower my intake of spasm meds. Taking 4-AP does wonders for me. I hope i am doing the right thing. The drs in P.A. when they hear TM they are like ? thanks anty

[~MAVERICK~]

Dr. Wise,
Can you please put more light on Bone Marrow "Mescnchymal Stem Cells". There is a hospital in Manipal, India where they have started clinical trials for SCI using Bone Marrow "Mescnchymal Stem Cells". However for now they are accepting patients only less than 6 months post SCI. Is there any other research/clinical trials of such nature conducted anywhere in the world? If Yes what are the results/implications? Also is this the same as "Autologous Bone Marrow Stem Cells which is being conducted by cells4health in Turkey.

Hope to get some valued inputs from you on the same.

Regards,
Melwin M

Bone marrow and umbilical cord blood contains cells called "mesenchymal stem cells" that can produce many kinds of cells but only under very special circumstances. In fact, if you transplant mesenchymal stem cells into injured adult spinal cord, the cells usually do not produce neurons or any other kind of cell. If it does make cells, it makes more of itself. This is because the adult spinal cord does not contain the factors that are necessary to stimulate the mesenchymal stem cell to produce other kinds of cells.

On the other hand, several groups have reported the mesenchymal stem cells will stimulate remyelination and, in some circumstances, may themselves help remyelinate axons. Because there is no definitive marker for mesenchymal stem cells, it is hard to get a pure culture of such cells from bone marrow, umbilical cord blood, or peripheral blood. One is usually transplanting a mixture of cells that include some mesenchymal stem cells.

[alan]

So a C-4 or C-5 wouldn't get hand function back?

[Meredith Tate]

Dr. wise Young,
I saw your name in conjunction with information on olefactory stem cells. I have seen information on Olefactory stem cells dating back to 1999 (it probably goes back further) I have read about Dr. Lima's work in Portugal and I wonder why we have not taken the olefactory stem cell and run with it. It seems it has potential to cure and does not require immunosupressant drugs. I wonder why the politicians are fighting over fetuses when there are olefactory cells in all of us. One of my favorite quotes ,"The last time politics and religion mixed, people were burned at the stake) But then I wonder why, in the greatest country in the world (which I think we are) there exists a dark ages protocal for SCI recovery, one which lessens one's chances of recovery.

[teesieme]

TY so much Wisey for taking such care in your explanations regarding stem cells and inquiry of. I am beginning to understand more and more, what is what and how with whom, etc. I really appreciate you so much!!! ~ Teresa

[Wise Young]

Originally Posted by anty

Ok dr. wise in my case with TM what would be good for me you saw my mris. I am waiting for a bike for my house to build up some more muscle in my legs and try to lower my intake of spasm meds. Taking 4-AP does wonders for me. I hope i am doing the right thing. The drs in P.A. when they hear TM they are like ? thanks anty

anty, I am glad that 4-AP is helping you. Transverse myelitis can have so many causes (or even no identifiable cause) that I think that it is difficult to come out with any generalization about the condition. Some people recover a lot and others do not. In some cases, TM may be due to ischemia of the spinal cord while, in others, it may be demyelination due to inflammation. It is possible that you have the latter and this may be why 4-AP is improving your function, since the drug works mostly by improving conduction of demyelinated axons.

Wise.

[Wise Young]

Originally Posted by ~MAVERICK~

Dr. Wise,
Can you please put more light on Bone Marrow "Mescnchymal Stem Cells". There is a hospital in Manipal, India where they have started clinical trials for SCI using Bone Marrow "Mescnchymal Stem Cells". However for now they are accepting patients only less than 6 months post SCI. Is there any other research/clinical trials of such nature conducted anywhere in the world? If Yes what are the results/implications? Also is this the same as "Autologous Bone Marrow Stem Cells which is being conducted by cells4health in Turkey.

Hope to get some valued inputs from you on the same.

Regards,
Melwin M

Melwin,

For many years, doctors always meant hematopoietic (blood-producing) stem cells when they referred to bone marrow stem cells. However, in late 1990's, several groups reported that they were able to grow cells from bone marrow that produced cells other than blood and related cells. Although nobody had a marker for the cells in bone marrow, they were referred to as "mesenchymal" stem cells, meaning that these are stem cells that develop into connective tissues, blood vessels, and lymphatic tissues. In 1999, Dr. Ira Black at the Robert Wood Johnson School of Medicine reported that some bone marrow cells were able to make neurons, giving credence to the hypothesis that there may be pluripotent stem cells (cells that can make all the major cell types of the body).

Mesenchymal stem cells have now been isolated for a variety of tissues, from peripheral blood, skin, joints, and others. Many studies have reported beneficial effects of so-called mesenchymal stem in various conditions but unfortunately there is no standard for isolating and identifying these cells. In the last four years, much excitement has surrounded the possible effects of bone marrow cells on the heart. Several clinical trials of mesenchymal stem cell therapy of cardiac conditions, such as after myocardial infarcts and congestive heart failure, have started. Because the treatment seems relatively innocuous, i.e. one simply takes one's own bone marrow cells, expand them in culture, and then reinfuse the cells intravenously. Since these are the person's own cells, the possibility of a reaction is low. Furthermore, in many cases, if one does not manipulate the cells, doctors can go ahead and do this kind of procedure without even having to get FDA approval.

The evidence that mesenchymal stem cells are useful for spinal cord injury, in either animal or humans, is still quite limited. While some animal studies have suggested that implantation of bone marrow cells into the spinal cord can stimulate remyelination, there is some controversy whether the transplanted cells are actually responsible for the remyelination. The cells may be secreting some factors that are stimulating endogenous cells to remyelinate the spinal cord. A few studies have even suggested infusion of the cells intravenous may be useful. I want to point out, however, that there is a crucial difference between most human and animal studies. In most humans, the cells used are autologous while, in most rodent studies (since it is difficult to collect bone marrow from them), the cells are obtained from another rat and some immunosuppression may be involved.

Several clinics (including Cells4Health in Brussels, the clinic that you are referring to in India, and others) have been reportedly trying to do clinical trials. I am in San Francisco at a stem cell meeting where several groups have been reporting their results and suggesting that bone marrow stem cell treatments are having beneficial effects on their patients. Dr. Amit Patel, for example, at the McGowan Institute in Pittsburgh is convinced that bone marrow cells are having beneficial effects on the heart. In the next year or two, the clinical trial results will come out and I think that we will know whether mesenchymal stem cell therapies are effective. In the meantime, many clinics are rushing in to make money from the procedure.

You ask whether Cells4Health and the Manipal hospital are using the same cells. I don't know and probably they don't know either. Cells4Health, for example, do not disclose the procedure that they use to isolate cells from the bone marrow. They keep the procedure proprietary. Most centers have been selecting cells from bone marrow that display CD34 or CD133, enriching them for these two types of cells. However, it is important to point out that neither of these markers are true stem cell markers. While some stem cells may display CD34 or CD133, not all cells that display these markers are stem cells.

Wise.

[Wise Young]

Originally Posted by Meredith Tate

Dr. wise Young,
I saw your name in conjunction with information on olefactory stem cells. I have seen information on Olefactory stem cells dating back to 1999 (it probably goes back further) I have read about Dr. Lima's work in Portugal and I wonder why we have not taken the olefactory stem cell and run with it. It seems it has potential to cure and does not require immunosupressant drugs. I wonder why the politicians are fighting over fetuses when there are olefactory cells in all of us. One of my favorite quotes ,"The last time politics and religion mixed, people were burned at the stake) But then I wonder why, in the greatest country in the world (which I think we are) there exists a dark ages protocal for SCI recovery, one which lessens one's chances of recovery.

Meredith,

Dr. Lima has been transplanting nasal mucosa (the lining of the nose). It is unclear how many olfactory ensheathing glia or other cells are present in the transplants. He has variously claimed that he is transplanting olfactory ensheathing glia and then stem cells into the spinal cord. I think that both of these claims cannot be justified. He is transplanting nasal mucosa into the spinal cord and it is not clear olfactory ensheathing glia or stem cells are being transplanted.

To date, nearly a dozen people from CareCure have had the Lima operation. While several have reported some benefit from the surgery, many have not. You may be interested to look a the following thread where there is a poll concerning recovery after the Lima procedure http://carecure.org/forum/showthread.php?t=17817 and about 20% of the people report that they had substantial recovery, 30% say they had slight improvement, and the rest said that they had no recovery or got worse. So, the chances of beneficial effect 50:50. A person has about equal chances of getting worse as they have of getting better.

Wise.

[Wise Young]

Originally Posted by alan

So a C-4 or C-5 wouldn't get hand function back?

Alan, it depends on the injury. The biceps receives innervation from the C4, C5, and C6. The motoneurons for the wrist extensors are at C5, C6, and C7. The motoneurons for triceps are at C6, C7, and C8. The motoneurons for hand are in C8 and T1. So, if a person has a C4/5 injury, the motoneurons for the hand should still be intact and regeneration alone should be sufficient to help restore function to the hand. One would not necessarily need neuronal replacement.

Wise.