Interstitial Stem Cell Bank in Tianjin, China

Some interesting news coming out from China. This article mentions that an "interstitial stem cell bank" was inaugurated in Tianjin a few days ago. It is managed by the China National Engineering Center of Cell Products (NECCP) but it isn't clear from the article whether this a private set up or a public funded project. The head of the Center, a gentleman Wang Fu sheng suggests in his statement that the center plans to engage in cell therapy of injured tissues and organs, especially in cancer, nervous diseases and skin tissue for burn patients.

The article mentions that these stem cells are usually taken from the marrow but can now be isolated from the "navel string" which I think is a literal translation of the umbilical cord. I'm not sure if its umbilical cord tissue or whether they isolate the stem cells from the cord blood, in which case would make it an umbilical cord blood stem cell bank.

Cryo-Cell International Inc. changes from Vials to BAGS conforming to US AABB Cord Blood Stem Cell Banking Standards

I read recently that one of the oldest and largest banks in the US has recently announced their financial results and described at the same time that they had made a fundamental change in the way they bank cord blood stem cell units, resulting in a 5X increase in their price of cord blood banking.

The recent Cryo-Cell International Inc. (OTC Symbol: CCEL or CCCEC) First quarter results for 2006 showed that although revenues were up by 12% from 2005, cost of sales was up by 7% and marketing, general and administrative expenses were up by 5%, all compared to the first quarter 2005.

The increase in cost of sales was attributed to:

1) Increased cost in lab supplies
2) Sales Promotions and Cord Blood Collection Reimbursements
3) Service Enhancements

The 1st point involving lab supplies increase was due to "the Company's April 2005 implementation of a new processing methodology in accordance with newly established standards of the AABB (formerly known as American Association of Blood Banks). The new process utilizes closed-system bags in place of vial storage".

With regards to how they are going to maintain their on-going financial strength, Cryo-Cell International Inc has raised their prices of cord blood stem cell banking.

Cryo-Cell Price Change to reflect change in storage system:

Vials Storage- USD 315 (initial), USD 50 (on-going). ie. RM 1170 (initial) and RM 190 (yearly)

TO

BAG Storage - USD 1,595 (initial), USD 125 (on-going). ie. RM 6,061 (initial) and RM 475 (yearly)

This means that Cryo-Cell's cord blood stem cell banking program has increased by 5X and yearly by 2.5X.

What this price increase does show is that lab consumables when using a bag system is more expensive than vials. However, due to the new safety regulations on cord blood banking, cryo-bags are now the standard. It may be merely a matter of time before most stem cell banks using vials change to the bag system in order to conform to international standards.

Analysis and Reasoning:

Coming from the angle of usage, many proponents of vials argue that by storing in several vials, a patient may be able to use each vial for a single treatment. However, this is misleading especially since:

a) ex-vivo expansion is not readily available and expensive
b) not every bag of cord blood collected contains sufficient cells for splitting into multiple vials
c) thus far, transplanters have used whole bags of cord blood and now propose using double cords to constitute sufficient numbers.

However, from the angle of safety:

a) bags use closed system processing (cells not exposed to air during transfer stages)
b) In handling of the bag, cells won't be spilt (unlike vials, potential spillage if mishandled)
c) Labelling safety- the unit is kept as one
d) Better risk management for transplant (no popping of cap or transfer needed when it comes to an IV line)

I also read separately that Cryo-Cell made a licensing agreement with an Indian company called Lifecell. Lifecell pays licensing fees to Cryo-cell Intl. Inc. for its set up and operations- with licensing fees contributing approximately 10% of Cryo-cell's topline revenue. It is unclear to me from their website whether Lifecell in India uses bags or vials for cord blood stem cell banking and if they currently use vials, when or if they will also make the change to bag systems.

But, looking at the prices that Lifecell charges since its launch in November 2004:

Enrolment & Processing = 27,000 Rupees (USD 599 ; RM 2,183)
Yearly storage = 2,900 Rupees (USD 64 ; RM 234)

And taking into account that Lifecell started in late 2004, perhaps they may not be using the bag system.

I wonder if our competitor in Malaysia (check out their amusing blog here) will continue trying to promote the benefit of vials given the clear (yet expensive) message that Cryo-Cell sends by changing all of their processes and systems to accomodate the benefits of storage in bags. At StemLife we thought about these issues carefully from our inception, which is why we have always stored in cryo bags and only cryo bags, in spite of the temptation to choose relatively inexpensive vials.

BOTTOM LINE:
Cryo-Cell's announcement confirms the decision of StemLife, Malaysia's first stem cell bank and therapeutics company, to use bags for stem cell storage rather than vials. As Malaysia's first and only company* to have also used stem cells stored in bags, we have first hand knowledge in assisting doctors in the thawing and use of stem cells for therapies when the patients need them. All stem cell units released from our bank have successfully engrafted, a testament that StemLife's cryopreservation procedures are valid.

*StemLife has expanded now to Thailand where Thai StemLife also uses the bag system of stem cell storage. Additionally, we have clients banked from Indonesia and Singapore where they have chosen StemLife's stem cell banking program for their babies' cord blood stem cells.

Misleading Bangkok Post article on Thailand Cord Blood Stem Cell Banking Availability

I read an article written up in the Bangkok post about Thai mothers "flocking" to bank their baby's cord blood stem cells at a foreign cord blood bank due to the service being unavailable in Thailand according to Thai Health Authorities. What the article failed to mention is that a local stem cell bank - Thai StemLife- has been operating and banking for expecting parents in Thailand since July 2005.

Additionally, the article quoted a doctor who mentioned that about 10-15% of mothers birthing at a reknown Bangkok Hospital were spending VAST amounts of money to do so (1st year 50,000 baht [USD 1,320], subsequent years 6,000 baht [USD 159]).

Thai StemLife is a joint venture between StemLife in Malaysia and reputable doctors and hospitals in Thailand. The entity, which is majority Thai owned, follows StemLife Malaysia's structure in laboratory operations and some co-marketing activities to leverage on cost saving functions. Thai StemLife has its own passionate and professional management who work hard to establish committment, credibility and great service to their clients. Clients are welcome to visit and tour Thai StemLife's facilities at the Central World Tower which boasts state of the art security for client's stem cells, full power back up and modern lab facilities rivalling those internationally.

Another mistake or perhaps misquote in the article states that the storage life of the cord blood cells is 20 years according to the CEO of the foreign bank. Actually, stem cells properly cryopreserved may be stored for longer than that, almost 20 years of data is already available- so there is no reason why stem cells can't last 30, 40 or even 50 years under the right conditions.

Thai parents, you can save a bit of money and see the tank your baby's stem cells are stored in just by dropping by Thai StemLife at Central World Tower (its even next to a convenient BTS stop!). Additionally, you could ask them who they've banked stem cells for and if your baby's stem cells are next to any famous babies... :)

Check out Thai StemLife's website here.

Or contact them directly:

THAI StemLife Headquarters
Address : 23rd. floor. The Offices at Central World.
999/9 Rama I rd. , Patumwan
, Bangkok 10330
Tel : +66(0)2 613 1515-8
Fax : +66(0)2 613 1519
Email : info@thaistemlife.co.th
24 Hr Hotline : +66(0)1 3407676

Reports of Stem Cell Transplant for treatment in Hurler Syndrome and Leukemia

Two patient cases reported recently needing stem cell transplants to treat their condition.

The first story is about a 1 year old boy Justin Wolford with Hurler syndrome who gets an 8 hour weekly enzyme replacement injections at Hershey Medical Centre. However, the enzyme injection is only temporary and the only way to slow the progression of the disease (85% chance of stopping) is a stem cell transplant. Hurler syndrome (otherwise known as muccopolysaccharidosis Type 1) is debilitating on the growth of children and are progressively neurologically impaired with a possibility of early death. Gone undetected, he could have been faced with a life of progressing mental retardation, hearing loss, clouding of the eyes and spinal deformities. Eventually, the mother said, his organs would have begun to shut down.

Unfortunately, his only 7 year old sister was not a match and a matching unit is in the process of being found.

Malaysia has a number of Hurler syndrome sufferers (US estimates of incidence is 1 in 25,000 but I couldn't find any numbers for Malaysia) and I wonder if they are aware that with an early diagnosis and stem cell transplant, their child might have a decent chance of living quite normally. StemLife did have one enquiry for this condition, but the child was already of significant age and there was a significant risk associated with the procedure.

The next story is about an 8 year old boy, Zachary McCracken, who has been fighting acute lymphoblastic leukemia for three years but relapsed and received an umbilical cord blood stem cell transplant last week. Three months ago, the McCrackens were hoping to find a bone marrow match for the boy. Hundreds of the boy's neighbours donated blood during a December fund drive at the boy's school, but the family was unable to find the right match. They had little choice but to search for a suitable unit of cord blood, but the article does not specifiy where they obtained the unit. The transplant was conducted at Duke University Hospital and the parents will wait out the 4-6 months until their son is able to leave the isolation room.

Zachary McCracken and his recovery is available online. Fingers crossed for both these young patients. The StemLife team hopes they are able to return home soon.

Heart Attack Trial Treatment by Mesenchymal Stem Cells

A new study has just been announced at a Centre in Illinois that Osiris is funding and supplying mesenchymal stem cells obtained from healthy volunteer donors' bone marrow in a trial for those who have had a single heart attack. The interesting thing about this trial is that there are several deemed advantages from the patient's perspective:
1. No match required! 2. Infusion through a standard IV line, no angioplasty or surgical procedures required.

“A person who has had a single, severe heart attack may survive but can be left with substantial damage to the heart muscle as a result of the blood supply to the heart muscle being cut off during the heart attack. The damaged muscle inhibits the heart's overall ability to pump blood, leading to heart failure,” said Rush principal investigator cardiologist Dr. Gary Schaer, head of the Rush Cardiac Catheterization Laboratory. Rush is the only center in Illinois participating in the trial. There are 15 other sites nationwide participating in the study."

It is thought that the mesenchymal stem cells (MSC) are in the early stages of development and thus do not trigger an immune response when placed in someone else's body. And since adult stem cells are designed by nature to perform tissue repair in mature adults, it is believed that these cells can be used without fear of rejection and promote healing in damaged organs by "homing" into the site of injury. The doctor conducting the trial says that the stem cells know how to go to the heart after a recent heart attack.

Osiris grows the cells in culture to very high numbers, allowing a single donor's cells to treat thousands of patients. The cells are then frozen at Osiris and taken out for distribution or use when required. The article doesn't state how much each infusion costs nor how many cells need to be administered (probably by body weight as they had announced in a previous trial). As the cells may have a multipotential lineage, I wonder if the doctor will also be monitoring other organ functions at the same time to see if there is a global improvement in the patients receiving these stem cells.

According to the article: "The Phase I study is double blind; two thirds of the participants receive the stem cells and one-third receive a placebo. To be eligible for the trial, patients must have experienced a first heart attack within the past seven days, and are between 21 and 85 years old. Patients are given a pulmonary breathing test, a CT scan and an MRI before the procedure. Patients undergo an MRI at the end of the study to see how much of the diseased heart muscle has been repaired and measure heart function. A patient may stay in the hospital only 2-3 days for observation, and then go home. The total time commitment for the study is two years."

If Osiris succeeds in improving heart attack in this trial, the role of cardiologists and cardiac surgeons may change profoundly in the way that a patient is treated. This is revolutionary and exciting news and Osiris might just live up to its name of the god of death and resurrection.
Imagine... just a shot of mesenchymal stem cells, could change the lives of hundreds of thousands of patients living with heart disease and perhaps reduce the possibility of sudden death in Malaysia.

StemLife attends Cancer Immunotherapy Workshop at Nilai Cancer Hospital, Malaysia

StemLife was invited to attend a special Cancer Immunotherapy Workshop at the new wing of NCI Cancer Hospital (Nilai Cancer Institute- Cancer Hospital= NCICH) organized by a local company specializing in bringing viable health and scientific related products to markets in South East Asia and Islamic countries.

In this particular event, the company brought in speakers from 3 Cuban research institutions with the aim of introducing and showcasing Cuba’s R&D strengths and new products to Malaysia. Attendees included a motley crowd of scientists, physicians, academics and students.

The 2 product lines from Cuba include Cancer vaccines known as EGF, TGF and Her-1, which are claimed to target 60% of all cancers. The animal and human trials have already been conducted in Cuba but they will launch Phase II trials in Malaysia, China, India and the US (via US licensees) in 2006 for regulatory approval. The other product line is a nutritional supplement of proteins for faster fish growth and enhanced immune capabilities against environmental insults. A field trial is currently being conducted in Mersing.

The main issues raised by the Cuban General Director for the Centre of Molecular Immunology, Dr. Agustin Lage (pronounced La-hey) was whether biotechnology from developing countries would ever be able to rival or match biotechnology countries in the US and Europe which have between them more than 85% of the top biotechnology companies in the world.

He also brought up the topic of regulation by governing bodies of new and foreign drugs, where the concept originated as appropriate scrutiny for the safety and gradually was used or construed in a manner which became a manner of economic protection. Citing the example of the rotavirus vaccine, due to 20 deaths that happened in infants, the vaccine was withdrawn from public use. In developing countries where rotavirus causes the most damage, the withdrawal of the vaccine inadvertantly caused some 500,000 infant deaths. He expressed the hope that the ethics of the west would not prevail as the ethic for developing countries without considering the local impact and consequences.

A question was raised by a member of the audience regarding Cuban's high retention policy of scientists and doctors, in contrast with Malaysia's problem of "brain drain" to neighbouring countries offering double the amount in renumeration. Dr. Lage replied saying that in Cuba, doctors and scientists were inspired to stay on by forming a well developed unit and their own objectives. Though the Institutes were state-owned, the policies, staffing and direction of research was very much in the control of the individual groups who aim to create the maximum amount of impact of society through their work.

Malaysian scientists could be rewarded with equal treatment and meritocracy, respect, access to research grants and a real collaborative as opposed to competitive atmosphere; there should be no problem in nuturing the biotechnology sector and preparing graduates for a worthwhile, noble yet promising career.

Apart from the production of cigars, sugar and shellfish, Cuba appears to be ready to export some expertise and biotechnology products to Malaysia. I asked Dr. Lage about stem cells in Cuba, but he didn't think that there was any development in that area in Cuba, which isn't really surprising if the focus is on manufacturing products for export.

Anyway Dr. Lage, I found some information on the use of stem cells in limb ischaemia and heart disease in Cuba. So, it is happening albeit on a small scale at local medical institutes.

Clinical Trial Using Stem Cells from Peripheral Blood and Umbilical Cord Blood to treat HIV (AIDS)

A recent report published on stem cells (from umbilical cord blood, peripheral blood) and HIV recently prompted me to find out exactly what this branch of research involved and how 70 HIV positive patients in California fared with this elegant and hopeful combination of molecular biology and cellular biochemistry.

It was elucidated that an enzyme known as "ribozyme" (as seen in above picture) could be created with an activity that enables it to cleave the mRNA* strand of the HIV-1 virus (*mRNA stands for m=messenger RNA= RiboNucleic Acid). mRNA is an important component in viral replication as it serves as a "template" strand which codes the proteins to form the structures of many more HIV viruses. Essentially, if you can halt the formation of the template, you can prevent the formation of any meaningful viral particles, rendering the virus non-infectious. The ribozyme acts as a special biochemical scissors to snip the template at specific sites and prevent template formation and further virus manufacturing.

Research on this area of enzymic activity has been conducted for more than a decade now, since the early 90's and much funding has been contributed to finding an effective vaccine. The reasons why a vaccine has remained elusive for so long are:

(1) Understanding of viral replication & its susceptible points
(2) Mutation of the HIV virus genes (i.e. different mRNA's need different types of scissors)
(3) Different strains of HIV (different gene coding, which strain is more important?)
(4) Possible side effects of vaccines on a weakened immune system

What lead researcher Ronald Mitsuyasu of the University of California, Los Angeles’s Center for Clinical AIDS Research and Education and UCLA virologist Jerome Zack did was to engineer a ribozyme especially for the cleavage of HIV-1 mRNA at various sites, attach the ribozyme sequence to a mouse viral vector (penetrates human cells to deliver its genetic contents but is otherwise harmless) and expose it to human bone marrow and peripheral blood stem cells.

"The mouse virus carries the enzyme into a cell, where it becomes part of the cell’s natural machinery and fortifies it against any attempts by HIV to infect it and begin making viral copies. The stem cells are then reinserted into the donor’s body, where they begin making numerous copies of immune system cells that are resistant to HIV. This effectively prevents infection of the cell and if already infected, prevents its ability to pass on the infection.

The HIV virus attacks several different types of blood cells that are part of the immune system. "If you can target the blood- forming stem cell, that cell gives rise to all blood cells," said virologist Jerome Zack of UCLA. "So, therefore, if you could protect that cell, then every other cell derived from that would be protected."

Dr. Zack hopes stem cell therapy could be a better strategy for fighting the virus.

Dr. Mitsuyasu recently finished an initial clinical trial to test the safety of the treatment. The 10 patients in the trial didn't have any problems, and after three years, the HIV-resistant blood cells could still be detected.

Dr. Mitsuyasu is currently enrolling people in a trial to test the stem cell therapy. Patients are first given a growth factor (GCSF) that stimulates bone marrow stem cells to enter the bloodstream. Then blood is drawn and the patients' own stem cells are isolated from the blood. Next, the gene is inserted into the cells by a modified, harmless virus related to HIV. Then the stem cells, armed with their new weapon, are returned to the bloodstream where they begin making all the different types of blood cells, each of which will inherit the new anti-HIV gene.

According to the article, the method can protect about 10 percent of the patients' stem cells, but as the HIV virus slowly kills the vulnerable cells and protected cells continue to replicate, the percentage will increase. To speed up the process, six months after receiving the infusion of modified cells, patients will stop taking their antiviral medications for four weeks to give the HIV virus a chance to kill off some unprotected blood cells, putting pressure on the protected cells to replicate faster.

This exposure process is repeated again after 12 weeks when the patients go off their medication for at least eight weeks, and potentially longer depending on how well the strategy works to reduce the level of HIV in the patients' blood.

"If this works, even though it may not cure the disease, it certainly would allow patients to go for periods of time without therapy," Dr. Mitsuyasu said. "And that will make a big difference both in terms of the rate at which resistance develops to these medicines as well as all the side effects associated with having to take the medicine for the rest of their lives."

If this model can be developed for HIV, it also has great potential for use in other viral therapies affecting other types of rapidly regenerating stem cells in other organs. I'll mention a little more about how stem cells have been used in treating HIV patients in another entry... this one's getting a little long :).

Paralysis Surgery now in China- Umbilical Cord Blood Stem Cells & Olfactory Mucosal Stem Cells?

Previously, I blogged about the use of olfactory mucosal stem cells* in an attempt to heal the injured spinal cord of Jacki Rabon. Now, another article published in the Weschester Journal describes the use of it in Beijing. Dr. Hungyun Huang will perform a similar procedure for another 23 year-old spinal cord injury patient, Christan Zaccagnino, to that conducted in Portugal.

The article states that whilst there is no success rate documented, and the surgery has not been approved in the US (hence, Lisbon, Beijing and Brisbane). But Dr. Wise Young, a Rutgers University professor and neurologist who has studied the surgery, said each of the dozen of Huang's patients he has spoken with had more sensation and some muscle strengthening after the procedure, according to a forum on the Web site of the W.M. Keck Center for Collaborative Neuroscience at Rutgers University.

According to the "Cure Paralysis Now" advocacy group website, Dr. Wise Young from Rutgers University posted some notes from Dr. Hungyun's paper:

Hungyun Huang and colleagues recently published a paper in the Chinese Medical Journal (2003, 116:1488-91) reporting the neurological results on the first 171 patients into whom they transplanted olfactory ensheathing glial (OEG). The patients ranged from 2 to 64 years of age, were mostly male (139, female 32), and were 6 months to 18 years after injury (average 2 years after injury). The cells were cultured from olfactory bulb of aborted human fetuses. The spinal cord above and below the injury site was exposed by laminectomy. Approximately a half million cells were injected into each of two sites, above and below the injury. Improvement was shown in the motor score, touch score, and pinprick score in the patients at 4-6 weeks after transplantation for each age group. Approximately 71% of the patients were ASIA A (complete spinal cord injury). There was no significant difference of recovery between the age groups.

During the surgery, Dr. Hungyun Huang of Beijing will transplant cells derived from stem cells in the lining of the nose into Zaccagnino's spinal cord above and below the spot where she was injured. Huang normally uses cells from aborted human fetuses, but Zaccagnino requested that he use cells from the frozen umbilical cord blood of her two young nephews instead (like the procedures performed in Korea by Histostem).

$$$ How much is the procedure?
USD 30, 000 for the procedure to take place in Beijing next April. Funds are now being raised by charitable donations organized by her family, friends and classmates.

It will be interesting to see the results of stem cells from umbilical cord blood versus olfactory mucosa lining, clearly there is big difference in the way that the stem cells can be obtained (cord blood does not require surgery, no controversy with aborted fetuses, no growth medium contamination problems) and if this can be repeated consistently with similar or equivalent results, will provide a lot more options for patients wishing to undergo this therapy.

*Olfactory ensheathing glia (OEG) are of particular interest because of their ability to facilitate regeneration and remyelination of the spinal cord. They are believed to be the reason why the olfactory nerve is the only central nervous system structure continuously regenerates in adults. However, umbilical cord blood derived stem cells have also produced significant recovery in patients under the same surgical procedure.

Update on Michelle Farrar's Spinal Cord Injury Procedure

The only way of knowing whether any surgery or medical procedure works is to communicate with the patient afterwards to understand whether their condition has improved or not.

In an earlier blog entry, I discussed the case of Michelle Farrar, who went to Korea for stem cell implantation into her damaged spinal cord. It was interesting to note that 4 months after the procedure, Michelle is showing signs of progress.

Upon returning back to the US from Korea, she was able to move her feet independently (apparently recorded on video but I can't seem to download it on my computer) but is for some reason unable to move them now. However, she has shown progress in a few other areas. She can do sit up crunches (good abdominal control), can use the bathroom unassisted and has feeling below the knees.

She could do none of these before the stem cell infusion.

The doctor responsible for her rehabilitation and care has called for a collaborative effort with the doctors in Korea and a large clinical trial. I think this is wonderful and spinal cord injury patients fitting the criteria should come forward to see if they may benefit as well.

Cost wise, the procedure is expensive (as are matching stem cells) for the hospitalization, medication, professional fees and although the doctors in Korea have been criticized for charging for a surgery deemed experimental, I think that unless philanthropists or a foundation would step forward to fund all the costs mentioned, the price tag is really about cost-recovery as opposed to profit (surgeries and cell therapy is expensive due to the level of care involved).

Furthermore, this procedure has to be customized according to the patient's condition and I'm really not sure if there can be "economies of scale" as this isn't a mass-produced manufactured drug.

So far, it looks like Miss Farrar is doing well and I hope that with the stem cells and rehabilitation, she's going to get back on her feet and on with life.I'm sure ABC 7 news will keep us updated in the next few months.

When One Cord Blood Unit isn't Enough- Double Cord Blood Transplant

Congratulations to Dr. Peter McSweeney of Rocky Mountain Cancer Centre in Colarado for their successful double cord blood transplant for an adult! Sheila Gannon was pregnant when she was diagnosed with leukemia and chances of survival was only 20%. Given very few options due to the lack of a bone marrow match, her doctor obtained 2 units of umbilical cord blood stem cells in order to make up the necessary cell numbers.

From her video testimony (check it out on the right hand side of the page), she is doing well, apparently in remission and getting back to normal life. At least she is able to spend time with her newborn baby son now that she's had her treatment. It must have been tough on the family.

Stem cell bankers: if one unit isn't enough, then combination of cord blood units may be performed to make up the cell numbers. The main point is "the more cells the better".

I have yet to hear of someone saying that one bag of cord blood was too much and only a small portion of it was used for their therapy. To date, everyone uses everything they have in the bag.... and when one bag is not enough... add another bag of matching stem cells! In Malaysia, we have some rather unscrupulous people who tell others that by storing a unit of cord blood stem cells in 5 vials instead of in 1 bag, that it can be used 5 times, for your mum, dad, grandpa, aunty, uncle and yourself. This has yet to be proven true and until such time, remains a myth. Anyone promising this should be asked for a letter defining the exact promise.

Today a Clinical Trial, Tomorrow a Standard Treatment

"When do clinical trials cease and when does it become a therapy?"

I get this question from my team whenever I discuss the latest trials that are going on for stem cells in other parts of the world, and I just got asked this question again today from my colleague.

I took the opportunity (during the last BIO 2005 conference I attended in Philadelphia) to pose the question to the prominent panel of scientists consisting of Prof. Wise Young of Rutgers, State Univ. of New Jersey and NIH policy advisor, Prof. Ruth Faden of the Phoebe R. Berman Bioethics Institute at Johns Hopkins University and Prof. Darwin Prockop, Director of Gene Therapy at the Tulane Univeristy Health Science Centre.The topic discussed was Stem Cells, the policy and legislation surrounding the issues of research and clinical trials.

Despite the accumulated brain capacity and years of experience in stem cells exceeding the entire collective of Malaysia, I gathered up my courage to ask them my question. "Sirs, in your talk, you mention many clinical trials that have been done and are on-going. May I ask -in your view of adult stem cell therapy- when is a clinical trial considered a therapy?"

The panel smiled at me kindly, and Prof. Prockop took up the microphone. He said "Young lady from Malaysia (I introduced myself before asking the question), a clinical trial is never just a trial, if it provides a cure for a disease which is incurable, it is not a trial. It is a therapy."

Many people are misled into thinking that by participating in a clinial trial, that the treatment is thought not to work. There are basically 3 stages of clinical trials, take for example cancer. The earliest stage, called phase I trials, are aimed at finding out about the side effects and the acceptable doses of new treatments. Phase II trials aim to find out how well the new treatment works. Phase III trials compare the new treatments with the standard one.

A treatment is better either because it is more effective against the cancer or because it is equally effective and has fewer unpleasant side effects. It is very likely that the treatment being given has already been tested for its effectiveness in a previous trial.

Today's stem cell trial treatment may be tomorrow's standard treatment, whether it be for cancer, heart disease* or diabetic foot ulcers. As long as the treatment does not do worse than the conventional therapy being offered (e.g. stem cell improving ejection fraction vs. nothing else offered by the doctor), it may be labelled a trial for the doctor, but as Prof. Prockop said- it is already a therapy for the patient.


*See previous entry on stem cells for heart disease- patients have already benefitted (therapeutic effect).

Preparation of a paediatric patient for cord blood stem cell transplant

Unless you have had a friend or family member with cancer, its quite unlikely that you would understand what the patient goes through on a day to day basis. The story that this entry is linked to is about an 8 year old's fight with Acute Lymphocytic Leukemia (ALL). The little girl has already had chemotherapy once to rid her of the disease, but the cancer has returned and she is no longer responding well to the usual cocktail of drugs. Fortunately, funds were not an issue for the family and a " very good matching" cord blood stem cell unit was found and reserved for her.

Treating cancer is serious business, chemotherapy and radiation therapy is extremely toxic and often many patients have side effects from this which either puts them off the treatment, or in cases with poor prognosis, lose their immune systems and succumb to infection or organ failure. I've had friends who have been through chemotherapy and the effects of the drugs can be brutal. But with the lack of sophisticated drugs which can accurately knock the tumorgenic cell out of its aggressive growth cycle, a stem cell transplant (or infusion to boost the immune system post chemo) may be the only answer.

This report gives quite a good overview of a paediatric cancer patient's battle with infection, chemotherapy side effects (vision, sores, poor appetite) , long and boring hospital stays, the 24 hour care required and the absence of visitors. After the transplant, the challenge is to ensure that no graft-vs-host disease develops.

In young children, stem cell transplants may be risky due to their weakened state. However, their positive attitude, care and support by their parents often helps them to make it through much better than older patients, who may not have the same amount of nuturing or emotional support. In our experience with patients undergoing this form of treatment, every bit of support to smoothen the path is greatly appreciated. StemLife takes every transplant case personally and every child that banks their stem cells with us is part of the StemLife family.

A 2nd Stem Cell Transplant, and a Chance at Life

A very nice story written from Oregon about a young lady only 22 years of age who needs a stem cell transplant. Amelia Worth was first diagnosed with Acute Myeloid Leukemia (AML, same condition that Angel was diagnosed with) in 2003. After chemotherapy and radiation treatments, she had her own stem cells harvested (adult stem cells, peripheral blood) and transplanted this into her own marrow. The transplant worked and she went into remission in Feb 2004. Unfortunately, in mid 2005, her condition deteriorated and she was diagnosed with myelodysplastic syndrome (MDS), which caused her bone marrow to stop producing blood cells effectively.

“The best donor would be a sibling, but I'm an only child,” Amelia Worth said. “So now we're trying to match my genetic markers with one of the seven potential donors my doctors have found.”

MDS is considered a pre-cursor to leukemia, which is why many of the symptoms are the same, but if she has a transplant and her body begins to produce blood cells more effectively, she could remain in remission. If the transplant doesn't work, or if she comes down with host-versus-graft disease (with someone else's stem cells), she could die. The situation is dire for most AML patients who develop MDS, and Amelia's doctors say her chance of survival is now about 19.8 percent.

Stem cell transplants are expensive procedures and the first transplant she went through used up most of her insurance money. Her friend who was suffering from leukemia came forward to pay for a new insurance policy before she died, which enabled Amelia to cover most of the medical costs for the second transplant. However, obtaining a matching stem cell unit is expensive and this cost is not covered by insurance.

“We're paying $1,500 for each test for a possible donor,” said the mother of the patient, Patricia Worth. (Cost of matching amongst 7 potential donors is 7x1500= USD 10,500!)

The biggest cost is the transplant, which alone has a price tag more than $500,000 at Oregon Health and Science University hospital in Portland. While their insurance, Blue Cross, will pay a great portion of the transplant cost, the Worths will be facing bills for around 20 percent of all medical costs, or for tests, procedures and consultations that aren't covered under the insurance policy.

I hope Amelia Worth finds a good match and makes it through her second transplant. She has a long way ahead of her.

StemLife attends Cord Blood Transplantation Conference in Biopolis, Singapore (3)

Sorry to break this up into 3 posts, its just easier to manage my thoughts whilst looking through my notes. There's much more detail but I'm summarizing the points which I feel are particularly relevant and important to StemLife.

On the 2nd day of the conference, the discussion moved onto expansion (increase in numbers) of umbilical cord blood stem cells. One of the major challenges in cord blood banking is having sufficient cell numbers to support larger adult patients. Prof. EJ Shpall joked that in Texas (where she works), the average weight of a typical patient ranges from 80- 100 Kg, almost one and a half times of what the average weight is in Asia. Thus, a transplant based on cell count and patient weight would "weigh" in at a disadvantage for those on the heavier side of the scale. Everyone agreed that if this challenge could be overcome, umbilical cord blood stem cell transplants for adults would be on prime time.

The 2 ways of improving engraftment from a cord blood stem cell unit:
A) Increase cell number by amplification of the necessary cells
B) Improve immunosuppression methods and achieve engraftment through better understanding of myeoablation and marrow interaction.

(A) was covered in extensive detail by Viacell's Dr. Michael Choi, Prof. Ian McNiece and Prof. EJ Shpall. (B) was described in some detail by Dr. Ping Law but much research is still in progress. In this entry, I will focus on (A).

Dr. Choi described the isolation and attempt at expansion of a rare stem cell known as the Unrestricted Somatic Stem Cell (USSC). These stem cells he said were found in extremely small numbers in cord blood and had multipotential capability of forming other tissue types. In addition, USSC's are also thought to require less immunosuppression and thus may be suitable for use in other individuals. Viacell plans to make this form of cellular medicine available to its 65,000 strong client base and others needing the service.
Prof. McNiece dug deep into the scientific detail of his experiments explaining the different cocktails of growth factors and stimulants he used to encourage the stem cells to grow. First of all, he starts off with 2 cord blood stem cell units. Let's name them UCB1 and UCB2. The outline of the experiment was to thaw UCB1, pass the cells through an automated machine (Clinimacs) which selects of a specific type of stem cell that he want to investigate, grow the stem cells in culture between 7x to 18x which may take a few weeks. When the cells have reached the desired numbers, UCB2 is thawed and both the expanded culture plus the uncultured unit are co-infused into the patient. To ensure that the patient's immune system recovers, GCSF is administered post transplant.

Essentially, stem cells take about a week to get to confluency (uniform growth to layer the entire surface of one flask, but several flasks are needed to get adequate cell numbers) and the McNeice method describes using only 10% of the cord blood unit as a seed culture.

In another experiment, 3 stem cell units were involved. Bone marrow, UCB1 and UCB2. Bone marrow was harvested and combined with a thawed UCB1. This combination was then selected for stem cells, expanded ex-vivo for 14 days which yielded between 7x-24x expansion. The patient was given the necessary high dose chemotherapy prior to the transplant and the cultured cells was infused together with a thawed UCB2. Additionally, the patient was given GCSF to ensure no lack of immune cells and to ensure the cultured cell survival in the body.

What are the problems with the existing method?
(1) Expansion numbers still cannot be well controlled or predicted- the range is very variable between 2x, 5x to 18x depending on the type of cells you're after.
(2) Cord blood units contain a type of stem cell known as CD34+. Upon thawing, the cells can be found in the unit. However, after a selection procedure, the total count can DECREASE by 400x! This may be very problematic for transplants as patients need the supporting cells as well.
(3) Thus far, all expanded products have used serum derived from animal sources (provides the nutrition for the cells to grow) and there is a concern about applying animal products in human use. However, a medium derived from human sources has yet to be developed which can provide the same growth support in the lab.

Prof. EJ Shpall's talk discussed the clinical aspects of transplanting ex-vivo expanded cord blood stem cells in the "University of Colarado Cord Expansion Trial" where they were trying to improve time to engraftment and to reduce the graft failure rate in patients. The study recruited 40 hematologic malignancies (blood cancers) and 3 breast cancer patients. The key difference from the studies mentioned before is that in this study, the CD34+ cells were selected out from the UCB unit, expanded in culture and then re-infused to the patient with the remainder of the UCB unit. This means that its the same as a UCB transplant except that specifically selected stem cells would be greater in number. The conclusion from the study was that it is feasible and suitable for adults.

Prof. Shpall's team also collaborates with Prof. McNiece's team (they have been doing so for a decade) and now both parties are also collaborating with Viacell to do the research in Singapore on expanded cord blood stem cell units for transplantation.

What's the final take on stem cell expansion? It's possible, but not yet well defined in protocol, cell yield or patient recovery. Many patients didn't make it through the procedure well (but in early stages of medical development, this is expected). And, no one has dared to breathe a price tag on it, because the culture methods are expensive and customized to each patient (Clinimacs selection sorters are also very pricey). More work needs to be done before this technology can be effectively commercialised for supporting stem cell transplants worldwide.

Until then, every cord blood stem cell unit collected must be maximised for numbers. The first step of collection is still fundamentally important, and if cell expansion succeeds, the benefit to patients will be even greater.

StemLife attends Cord Blood Transplantation Conference in Biopolis, Singapore (2)

A couple more interesting points made at the conference:

Prof. Takahashi presented a few slides on the use of umbilical cord blood stem cells in regenerative medicine. He showed data indicating that precious Mesenchymal stem cells found in UCB would deplete in number over time prior to freezing. Freshly collected umbilical cord blood has decent numbers of mesenchymal stem cells, important in regenerating bone, cartilage and other tissue. However, after 20- 25 hours, no mesenchymal stem cells could be isolated for differentiation and tissue formation.

This point reaffirms StemLife's policy of getting the unit to the lab for processing within 24 hours no matter where the cord blood is collected from. We invest much energy and time in ensuring that this logistics policy is adhered to, for the benefit of our clients in the future (never know when those Mesenchymals will be needed!).

Dr. William Hwang of the Singapore Cord Blood Bank (SCBB) was generous in sharing his data, and highlighted that the reason why umbilical cord blood was a good source was partly due to the Bone Marrow collection procedure's association with a risky 0.27% rate of mortality (i.e. 27 patients out of 100 patients!). Thus, umbilical cord blood would be a much less riskier source from which to obtain stem cells. He also pointed out that the SCBB could target the ethnic minorities in Singapore and serve their needs. In their hands, cord blood stem cell engraftment took 5-6 weeks in adults and a futher 5-6 weeks to obtain the equilibrium for immune stability. Another piece of good news, the SCBB also aims to support the stem cell transplantation program for Systemic Lupus Erythmatoses (SLE) which is already being conducted in Singapore. SLE patients take note.

The SCBB is a "public" bank but is supported and funded by charitable organizations, not government funding thus far (although they have expressed the liking for more governmental support). However they collaborate closely with government transplant centres which offer their services to the public. And yes, Singaporeans will still have to pay for cord blood stem cell units if they need them. How much? Check with your transplant centre.