Stem cell questions

[Wise Young]

Originally Posted by sheplola@yahoo.com

hi, i'm would like to know who is do reseach with cord blood stem cells for sci. i am now 7 month out from my injury & my wife & i stored our son's cord blood 19 months ago.

We are doing cord blood cell transplants for the spinal cord.

Please note that there is a chance that a son's cord blood may not adequately match the father. In general, a person has six HLA-genes that are important for preventing rejection of the cells. Three of the genes come from the mother and three from the father. If the mother does not have HLA genes that overlap with the father, than it is possible to get only a 3:6 match. In order for a reasonable chance of engraftment of umbilical cord blood to occur, one usually needs 4:6 match. Of course, the best would be 6:6 HLA match.

I should also describe the treatments and how the cells from umbilical cord blood are being used for spinal cord injury and other conditions:

Spinal cord injury

1. Engraftment into bone marrow. Umbilical cord blood has been used for over 20 years to treat hematopoietic disorders (these are disorders of blood production). Blood is made by stem cells in bone marrow. If the bone marrow has been damaged by disease or chemotherapy, one can infuse bone marrow cells, peripheral blood stem cells, or umbilical cord blood cells from another person into the recipient intravenously. If the donor cells are well-matched, the cells goes to the bone marrow and "engraft". Thereafter, these engrafted cells will make blood cells, as well as stem cells that can contribute to different parts of the body. If you don't do anything to kill some or all of your existing bone marrow cells, the transplanted cells tend not to engraft. The process of killing of your existing bone marrow cells is called myelo-ablation. They usually use chemotherapy to do so. The procedure is unlikely to work in the following circumstances:
• If you receive an infusion of HLA-matched umbilical cord blood without doing any myeloablation, the cells usually do not engraft.
• If you receive an non-HLA-matched umbilical cord blood after myeloablation, the cells will usually not engraft whether or not you do myeloablation.
• If you receive an infusion of non-HLA matched umbilical cord blood without myeloablation, the cells will not engraft and very unlikely to have any therapeutic benefit.

2. Transplant umbilical cord blood cells intrathecally. Intrathecal injection means that the cells are injected into the cerebrospinal fluid (CSF) surrounding the spinal cord. By the way, one cannot transplant umbilical cord blood directly into the CSF. One has to process the cells first and get rid of all the red blood cells (RBC). RBC's are toxic to the spinal cord and one does not want to inject blood into the spinal cord. So, the mononuclear cells (non-RBC) must isolated. In our experience with animals, none or very few of the cells get into the spinal cord. They tend to congregate on the surface of the spinal. Although some investigators claim that they cells are not rejected from the central nervous system, we have not seen this. They are almost always rejected within 4 weeks. It is true that the rejection is slower than in the periphery but the cells are rejected. So, in my opinion, if the cells are not HLA-matched, they will survive several weeks or perhaps several months at the most but they will eventually be rejected. If they are matched, they will probably survive but it is unclear that the cells will get into the spinal cord injury site. The chances that the cells will get into the spinal cord are probably better than if the cells are injected intravenously.

3. Tranplant intraspinally. Injecting the cells into the spinal cord is the best way to get a substantial number of cells into the spinal cord. However, as pointed out above, it is essential that the mononuclear cells (which includes the stem cells) be isolated and all the RBC's be removed. If the cells are HLA-matched, a certain proportion of the cells will survive and stay in the spinal cord for more than a few weeks. If the cells are not HLA-matched, the cells will be rejected within a few weeks.

So, in my opinion, all places that are giving non-HLA-matched cells intravenously or intrathecally are doing little or nothing for anybody. The cells are probably rejected within a few days. There is no evidence that they cells are engrafting in the bone marrow and the cells are very unlikely to enter the spinal cord and do anything there. If they are having some beneficial effect, it is through a mechanism that nobody knows anything about or understands. Most of the Carribbean and Mexican clinics do not offer HLA-matched cells.

The places that are giving HLA-matched cells intravenously will probably have longer survival of the cells but the cells are unlikely to engraft unless there has been myeloablation. By the way, if the myeloablation is done, it also caused immunosuppression and therefore enhances the survival and engraftment of the cells. Thus, I suspect that there will be little beneficial effects of such therapies as well.


Muscular Dystrophy

The studies that have reported effective treatments with umbilical cord blood for muscular dystrophy have used HLA-matched (or sibling cord blood) that do not have the muscular dystrophy gene and used myeloablation. They have also demonstrated engraftment in that the blood type and HLA of the blood changes to the donor type. This is proof that the cells have engrafted. All these studies used myeloablation. If you do not do myeloablation, the cells are very unlikely to engraft.

Note that if donor cell engraftment is successful, the bone marrow will thereafter produce mesenchymal stem cells that have the donor genes and therefore the cells will gradually replace the myoblasts in the muscle and therefore the muscles. Over time, the muscles will be replaced by muscles without the muscular dystrophy gene. Like all treatments of genetic disorders, the stem cells must come from a donor that does not have the genetic deficit. There is no point in transplanting cells that have the same genetic deficit.

The main question that is unanswered is the extent to which myeloablation should be carried out. If one does what is called "mini-myeloablation", i.e. that kills many but not all the bone marrow stem cells, the donor cells will engraft and you will get a mixture of bone marrow cells that produce the donor and recipient stem cells. This may be all right because the donor cells may be stronger and eventually the cells will be replaced by the healthy ones. It is likely that this will work for all the different types of muscular dystrophy, including limb girdle.

Note that only one group (in China) have reported successful use of cord blood engraftment to treat muscular dystrophy. Why has this been tried so little? For a long time, myeloablation and failure to engraft carried a relatively high mortality of 5-10%. This was considered to be too high a risk. However, in recent years, gentler myeloablation methods and better engraftment procedures have resulted in 95% or greater engraftment rates. Furthermore, doctors are now taking out some of the bone marrow of the recipient and storing the cells before the myeloablation, in case engraftment does not occur. In such cases, the bone marrow can be re-transplanted back into the patient. A recent series of umbilical cord blood transplants being used to treat thalamessia have shown zero mortality.

I hope that this is understandable. Please ask questions.

Wise.

[Wise Young]

Originally Posted by doha

nobody have been cured with stem cell yet there in no cure

I'm sorry

While it is true that umbilical cord blood has not yet been shown to "cure" anybody with spinal cord injury, umbilical cord blood now has been successfully used to cure thalassemia and other genetic conditions.

Wise.

[salmanaslam]

Originally Posted by Wise Young

We are doing cord blood cell transplants for the spinal cord.

Please note that there is a chance that a son's cord blood may not adequately match the father. In general, a person has six HLA-genes that are important for preventing rejection of the cells. Three of the genes come from the mother and three from the father. If the mother does not have HLA genes that overlap with the father, than it is possible to get only a 3:6 match. In order for a reasonable chance of engraftment of umbilical cord blood to occur, one usually needs 4:6 match. Of course, the best would be 6:6 HLA match.

I should also describe the treatments and how the cells from umbilical cord blood are being used for spinal cord injury and other conditions:

Spinal cord injury

1. Engraftment into bone marrow. Umbilical cord blood has been used for over 20 years to treat hematopoietic disorders (these are disorders of blood production). Blood is made by stem cells in bone marrow. If the bone marrow has been damaged by disease or chemotherapy, one can infuse bone marrow cells, peripheral blood stem cells, or umbilical cord blood cells from another person into the recipient intravenously. If the donor cells are well-matched, the cells goes to the bone marrow and "engraft". Thereafter, these engrafted cells will make blood cells, as well as stem cells that can contribute to different parts of the body. If you don't do anything to kill some or all of your existing bone marrow cells, the transplanted cells tend not to engraft. The process of killing of your existing bone marrow cells is called myelo-ablation. They usually use chemotherapy to do so. The procedure is unlikely to work in the following circumstances:
• If you receive an infusion of HLA-matched umbilical cord blood without doing any myeloablation, the cells usually do not engraft.
• If you receive an non-HLA-matched umbilical cord blood after myeloablation, the cells will usually not engraft whether or not you do myeloablation.
• If you receive an infusion of non-HLA matched umbilical cord blood without myeloablation, the cells will not engraft and very unlikely to have any therapeutic benefit.

2. Transplant umbilical cord blood cells intrathecally. Intrathecal injection means that the cells are injected into the cerebrospinal fluid (CSF) surrounding the spinal cord. By the way, one cannot transplant umbilical cord blood directly into the CSF. One has to process the cells first and get rid of all the red blood cells (RBC). RBC's are toxic to the spinal cord and one does not want to inject blood into the spinal cord. So, the mononuclear cells (non-RBC) must isolated. In our experience with animals, none or very few of the cells get into the spinal cord. They tend to congregate on the surface of the spinal. Although some investigators claim that they cells are not rejected from the central nervous system, we have not seen this. They are almost always rejected within 4 weeks. It is true that the rejection is slower than in the periphery but the cells are rejected. So, in my opinion, if the cells are not HLA-matched, they will survive several weeks or perhaps several months at the most but they will eventually be rejected. If they are matched, they will probably survive but it is unclear that the cells will get into the spinal cord injury site. The chances that the cells will get into the spinal cord are probably better than if the cells are injected intravenously.

3. Tranplant intraspinally. Injecting the cells into the spinal cord is the best way to get a substantial number of cells into the spinal cord. However, as pointed out above, it is essential that the mononuclear cells (which includes the stem cells) be isolated and all the RBC's be removed. If the cells are HLA-matched, a certain proportion of the cells will survive and stay in the spinal cord for more than a few weeks. If the cells are not HLA-matched, the cells will be rejected within a few weeks.

So, in my opinion, all places that are giving non-HLA-matched cells intravenously or intrathecally are doing little or nothing for anybody. The cells are probably rejected within a few days. There is no evidence that they cells are engrafting in the bone marrow and the cells are very unlikely to enter the spinal cord and do anything there. If they are having some beneficial effect, it is through a mechanism that nobody knows anything about or understands. Most of the Carribbean and Mexican clinics do not offer HLA-matched cells.

The places that are giving HLA-matched cells intravenously will probably have longer survival of the cells but the cells are unlikely to engraft unless there has been myeloablation. By the way, if the myeloablation is done, it also caused immunosuppression and therefore enhances the survival and engraftment of the cells. Thus, I suspect that there will be little beneficial effects of such therapies as well.


Muscular Dystrophy

The studies that have reported effective treatments with umbilical cord blood for muscular dystrophy have used HLA-matched (or sibling cord blood) that do not have the muscular dystrophy gene and used myeloablation. They have also demonstrated engraftment in that the blood type and HLA of the blood changes to the donor type. This is proof that the cells have engrafted. All these studies used myeloablation. If you do not do myeloablation, the cells are very unlikely to engraft.

Note that if donor cell engraftment is successful, the bone marrow will thereafter produce mesenchymal stem cells that have the donor genes and therefore the cells will gradually replace the myoblasts in the muscle and therefore the muscles. Over time, the muscles will be replaced by muscles without the muscular dystrophy gene. Like all treatments of genetic disorders, the stem cells must come from a donor that does not have the genetic deficit. There is no point in transplanting cells that have the same genetic deficit.

The main question that is unanswered is the extent to which myeloablation should be carried out. If one does what is called "mini-myeloablation", i.e. that kills many but not all the bone marrow stem cells, the donor cells will engraft and you will get a mixture of bone marrow cells that produce the donor and recipient stem cells. This may be all right because the donor cells may be stronger and eventually the cells will be replaced by the healthy ones. It is likely that this will work for all the different types of muscular dystrophy, including limb girdle.

Note that only one group (in China) have reported successful use of cord blood engraftment to treat muscular dystrophy. Why has this been tried so little? For a long time, myeloablation and failure to engraft carried a relatively high mortality of 5-10%. This was considered to be too high a risk. However, in recent years, gentler myeloablation methods and better engraftment procedures have resulted in 95% or greater engraftment rates. Furthermore, doctors are now taking out some of the bone marrow of the recipient and storing the cells before the myeloablation, in case engraftment does not occur. In such cases, the bone marrow can be re-transplanted back into the patient. A recent series of umbilical cord blood transplants being used to treat thalamessia have shown zero mortality.

I hope that this is understandable. Please ask questions.

Wise.

What is the name of that group?

[Wise Young]

Originally Posted by salmanaslam

What is the name of that group?

http://sci.rutgers.edu/forum/showpos...6&postcount=11

[deepee]

I received a mail from Dr. Huang stating that they will give treatment for LGMD.
They charge CNY 150,000 for first time and CNY 110,000 for subsequent treatments.
Email ID for contact is nrrfr99@gmail.com.
Any one who know about the clinic, the type of treatment offered and the success rate please inform.