Stem Cell Pathway
None.
That is the technique the body cells use to survive the critical period whenever there is low blood oxygenation to an area. The low blood supply reduces charging of the cellular battery (ATP). Without it, the cell wall potassium gates start to leak potassium out of cells, raising the voltage outside the cell wall. That makes the voltage dependent calcium ion gates to close down. Unless calcium neters the cell to switch on the cellular mechanisms, the cell stops working, and shuts down all operations .
This is similar to a car engine being swithched off.
In this state, the cell can survive for years as a dormant damaged, but NOT DEAD, area. The area remains inflammed, swollen, function deprived. It can be visualised best on a properly done single photon emission computerised tomogram using Technetium99 dye to give standard cross sectional images in all three planes as well as the six sided 3D images. See image alongside (Pink=normal. Blotchy red/bluish red=low blood supply. Deep blue=severe blood supply deficiency or dead area).
Why do we think of Stem Cells:
Because damaged brain is NOT ALWAYS DAMAGED FOR LIFE, especially if managed within about 5 years of injury, with lower response thereafter.
Where do we use Stem Cell Therapy?:
Stem cells are usually being used as a part of Clinical Trials or as Compassionate Ground Therapy when no other medical remedy is successful or available, and there are some theoretical grounds to believe that Stem cell usage may, I repeat, MAY give some benefit, by harnessing the body's own powers of healing. This work will be Experimental in nature, as per the rules and regulations as laid out in the Helsinki Declaration.
What is the scope of stem cell therapy in cerebral palsy (CP)?:
CP is now believed to be a genetic disorder, where the brain has abnormal susceptibility to hypoxic injury caused by pre-delivery, birth procedure, or after delivery complications arising within the first two years of life, maximally affecting the motor controlling pathways, but also a variable degree of damage to thinking, hearing, visualising and psycho-social behavior areas of brain.
In spite of that, some or many functions remain. Standard Therapists (OT + PT + Special Education + Speech) can work hard to train those remanining functions to perfection, improving quality of life to a good extent.
However, these improvements sooner or later reach a state of stagnant improvement. Additionally, they do not enhance Cognitive Powers, intellect, and related functionality.
At this stage, ONLY REGENERATIVE MEDICINE CAN WORK TO GIVE FURTHER IMPROVEMENT, comprising Hyperbaric Therapy (Click here for details) and STEM CELL THERAPY.
What is the scope of stem cell therapy in Autism Spectrum Disorder (ASD)?:
Now that is a complicated answer, because the Jury is still out on what causes Autism. We have some leads:
- Genetic susceptibility for:
- Decreased ability to excrete heavy metals and many toxins, especially Industrial effluents mixed up with ground water and food grown in such soil or fishes living in polluted waters.
- Decreased ability to synthesize body's required level of vitamin methyl cobalamin
- Decreased immmune functions leading to frequent Gut Dysbiosys, leading to absorption of substances that harm the body and irritate the brain
- Abmormal mirror image neurons
- There are many more things cropping up that we know or dont yet know
- Inflammation/ swelling/ hypoxia in specific areas of brain that have been shown by various workers to correlate well with symptoms of ASD
- SPECT Scan imagery of brain that almost always shows the same classical pattern to those trained to look for it.
Why do most Specialists pooh-pooh such ideas?:
The "medical" knowledge of most specialists, doctors, and autism experts is based on the "FREE ABSTRACTS" available on PubMed, the free online medical disease and drug therapy database of the US National Library of Congress. What they do not know is that this "Medical Library" has almost 100 databases, of which only PubMed or Medline is free as far as abstracts are concerned (Even here, most full text articles are only available on payment of $5 per article, which hardly anyone goes in for!). The remaining lines are restricted to US Authorised Personnel only, and the general public may access it only on payment of about $34 per article. Naturally, hardly anyone anywhere in the world goes that far.
Free Medline is meant to help doctors treat diseases with current or future drugs or surgical procedures (to an extent). All raw science data like neuroanatomy, pure physics (HBOT), toxicology, cancer, pharmacology, pathology, biochemistry, etc. are not mentioned in Medline. For example, if you search Free Medline for mercury toxicity (one of the culprits in Autism), you will find only a few dozen articles. But, on TOXLINE, a paid database, more than 4500 articles are available. Have these "Experts on Autism" accessed them? You bet they haven't !!!
Have they searched the paid databases on correlation of specific areas of brain damage with specific areas of autistic behavior? You know the answer!
How many paid searches have been done on the researches in progress for use of Stem Cell Therapy for Autism? You know the answer!
Regenerative Medicine Timeline:
- Repairs and revives damaged dormant brain cells to variable degree within 2 months
- Nerve remyelination followed conduction ability restoration occurswithin 4-6 months to restore brain to (other parts of brain or affected parts of body) communication link
- Thereafter, brain needs 6-24 months to acquire a variable degree of control over the reconnected body parts as with any CHILD BORN NORMALLY.
- Quality of follow up one-to-one Standard Therapies determines degree of improvement seen over the next 2 years.
Emerging place (= Still Experimental Therapy or Clinical Trial Stage) of Stem Cell Therapy in CP and ASD:
Stem Cell Therapy (STC) in ASD and CP is being tried to repair swelling, inflammation, hypoxia, reactivate brain stem cells, and also possibly grow some new brain cells, to see if we can significantly enhance the quality of life of these children, even though "CURE" is just not possible at this stage.
Before even thinking of trying STC, we must be sure of diagnosis.
STC and HBOT may revive some damaged areas of brain that was otherwise formed normally during fetal life.
But if the brain did not form properly (Down, Tuberous Sclerosis, Fragile-X, etc), or if there is a congenital storage disease (Tay Sachs Disease, Sandhoff Disease, Wilson's Disease. William's Syndrome, Phenylketonuria, Gaucher's Disease, Galactosemia, etc), then the outcome of STC/HBOT may be nil or even harmful, including fatal.
The outcome is also not yet clear in disorders like PANDAS, Rett Syndrome, Landau-Kleffner Syndrome, Niemann Pick's Disease, etc.
Some similar pure genetic fault induced metabolic or abnormal anatomy producing disorders may be added to this list in future as more data comes in.
Types of Stem Cells and their place
Embryonic Stem Cell:
There is a lot of hype on Embryonic STC (See picture on top of page).
Its LONG TERM (more than 4 to 5 years later) safety is unknown though potency of the STC is quite good.
The source of the stem cell is often questionable: Was it an aborted fetus with genetic abnormality or infection? Was it an extra fetus made during In-Vitro Fertilisation technique (Is not that fetus alive and would it not have grown into a full fledged human had it been implanted into a viable woman's womb, and hence, is it not murder to cut up that fetus to obtain stem cells?)
Even though embryonic stem cells are GROSSLY deficient in HLA tissue antigen markers that cause transplantation rejection, they DO HAVE a tiny antigenicity. A perfect donor to host tissue match is extremely rare except in identical twins. Still, Graft Versus Host Disease (GVHD) is not OBVIOUS by current methods of testing, but what happens at the micro level inside the body after the injection, is unknown. In addition, a very small risk of tumor formation is reported in medical literature after 4 to 5 years.
The amount of stem cells available is anyway very low in number. It needs to be cultured and often requires Cell Manipulation to obtain a therapeutic dose. During culture, after 5 to 20 passages, genetic changes have been noticed at the micro-array level. Their long term effect is not fully known.
Legally, Embryonic STC is in CLINICAL TRIAL PHASE in India.
Cord Blood Stem Cells:
Autologous (same patient to same patient) Cord Blood STC is safe and effective.
Here also, the available stock is small (20 ml of peripheral type blood only). Hence it must be cultured to get optimum quantity, with rare attendant risks as seen with Embryonic stem cell culture.
Long term viability on Cryopreservation is an issue. The longest stored cord blood is now about 16 years and more than 40% loss of viability reported so far.
Allogenic or Pooled Cord Blood is generally available cheaply.
All centers do not do tissue match, and even where they do it, a match of 4/6 is considered OK, but it is NOT 6/6 antigen match. Perfect tissue match is not available.
Except sibling matched cord blood (least chances of rejection), it is unknown if stock of pooled cord blood contains some cells from children born of mothers who had congenital malformations or diseases or infections, as the samples is often obtained from Hospital Labor Room waste.
Duration of survival inside body unknown (GVHR).
Risk of transmissible infections of unknown source cord blood is a rare possibility as living cells can’t be sterilized and there are no 100% foolproof tests to guarantee infection-free status.
Legally, in CLINICAL TRIAL PHASE in India
Just about to be permitted in US under stringent quality control.
Peripheral Blood Stem cells may be more important in future.
Peripheral Blood has Stem Cells but their relative concentration is too small. Hence they need to be cultured using growth promotibng factors. Some authorities also use HBOT or some drugs to to temporarily emenhance the release of stem cells from bone marrow to peripheral circulation before doing its harvesting. Such growth promoting chemicals may include Granulocyte Colony Stimulating Factor, etc. As per cirrent level of understanding, up to five times of cell division (passage) maty be OK but after that micro-array changes in the structure of genetic material occur with deletions here and there on the genetic chain. What the effect of that will be is still subject to study, since Micro-Array Genetic Research is still in its infancy. We are also unsure of the long term (= more than 4 to 5 years later) safety / efficacy needs more data.
Bone Marrow Stem cells
Autologous, Unmanipulated bone marrow derived mononuclear cells (high % of Stem cells) with no chemical added, has stood test of time as effective and safe, with virtually no risk of tumor formation. Since adequate stock is available, hence there is no need for culture. Its use in the same person avoids all risks, e.g. No infection, No allergy, No GVHD.
Currently, the scenario suggests that they may used as Experimental Therapy after full details are submitted to DCGI AND FOLLOWING ALL RULES and GUIDELINES IF ANY, GIVEN.
Are Embryonic Stems becoming Obsolete?
As per a news bulletin in "US NEWS" available from http://health.usnews.com/health-news/blogs/heart-to-heart/2009/03/04/why-embryonic-stem-cells-are-obsolete?s_cid=related-links:TOP, . A report from Israel published in PLoS Medicine in late February 2009 that shows embryonic stem cells injected into patients can cause disabling if not deadly tumours. The report describes a young boy with a fatal neuromuscular disease called ataxia telangiectasia, who was treated with embryonic stem cells. Within four years, he developed headaches and was found to have multiple tumours in his brain and spinal cord that genetically matched the female embryos used in his therapy. Though they are tamed in a petri dish to be disciplined, mature cells, research in animals has shown repeatedly that sometimes the injected (Embryonic) cells run wildly out of control —dashing hopes of tiny, human embryos benignly spinning off stem cells to save grown-ups, without risk or concern.
Even as the future of embryonic stem cells has dimmed, adult stem cell research has scored major wins evident just in the past few months… Such stem cells can be removed almost as easily as drawing a unit of blood, and they have been used successfully for years in bone marrow transplants. To date, most of the stem cell triumphs that the public hears about involve the infusion of adult stem cells. We've just recently seen separate research reports of patients with spinal cord injury and multiple sclerosis benefiting from adult stem cell therapy. These cells have the advantage of being the patient's natural own cells and the worst they seem to do after infusion is die off without bringing the hoped-for benefit. They do not have the awesome but dangerous quality of emi eternal life characteristic of embryonic stem cells.
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The importance of stem cells for medical research has never been greater, and the scientific and public clamour for unimpeded research is fully understandable. However, we must male sure the public understands that all stem cells are not the same or created equally.
Side Effects of BMSCT
- Pain at tapping site for 2 to 3 days.
- Mild nausea, headache and self limiting low grade fever after Intrathecal infusion for a day
- Usually child fit to go home after 4 to 5 hours of observation after the short Ketamine anesthesia
No other side effects as child’s own blood used.
- N0T ONE occasion for Follow Up Antibiotics
- At EVERY infusion, CSF for culture taken. EVERY time it has been sterile.
HBOT + STEM CELL THERAPY
This is a new pathway of Regenerative Therapy. Researchers like Barbosa & colleagues have tried out since early 2000 at Argentina for a variety of brain injuries. Stem Cell Therapy was done alone or in the middle of a course of 40 to 60 sessions of HBOT. Joint Therapy was significantly superior to STC alone.
Our Experience is similar in CP and TBI. In Autism, it causes high degree of Sensory issues for about 2 to 3 months, then settles down for superior progress, both clinically and on SPECT.