Launch of NOVUSSANGUIS

Today marks the launch of a new international research consortium called Novussanguis for cord blood and adult stem cells. Its founding members, Professor Colin McGuckin and the Jerome LeJeune Foundation plan to bring together key researchers to discuss and collaborate on the development of stem cells for clinical application.


The launch is held in Paris today and I'll provide some insights about it later on. Here's a snapshot of the launch program.

UK-Singapore Stem Cell Symposium I

Just to remind the world that the UK isn't behind in science (vis-a-vis the US), the British High Commission probably decided that this exhibition panel was important to remind everyone of the UK's key scientific achievements.

So, if you didn't already know or can't read the words in the picture, here's three that you might have confused as a US invention...

UK GREATS
1953: Discovery of structure of DNA
1978: Birth of first test-tube baby
1985: Discovery of hole in Ozone layer
1990: Invention of World Wide Web (bet you all thought this was from the US!)

Anyway, I mentioned in my last post that I'd tell you a bit about what I learned in the symposium. My apologies for the delayed write up.

The first lecture after lunch was by Professor Tariq Enver, Professor of Stem Cell Biology at Oxford and Director of Stem Cell Research at the MRC's Molecular Haematology Unit in the Weatherall Institute for Molecular Medicine.

Prof. Enver's talk was of interest to me for 2 reasons - inspiring content AND all the key ingredients of a good presentation:

1. Clinical relevance (patient's photos to inspire the right emotional context)
2. Clear introductory statistics for the uninitiated
3. Direct genetic implications of the research
4. A happy conclusion (very important)


WHAT IT WAS ABOUT

The story begins with the introduction of stem cells and their existence in babies' blood. The first question he posed to the audience was whether anyone knew what a "Guthrie card" was (when a baby is born, a small heel prick is performed to obtain the baby's blood, which is stained on a filter paper- known as a Guthrie card- and used to test for inborn metabolic diseases). Prof. Enver suggests that Guthrie cards can be kept for extended periods of time so that if a child is later found to develop certain types of leukemia, it would be possible to identify whether the indications of leukemia were there at birth.


WHY IS THIS IMPORTANT?

The reason why it is useful to know whether the leukemic cells are present at birth, is because if the cells are present at birth, doctors may choose to treat the patient with different medications as leukemic cells (which behave like stem cells) have different chemo-sensitivities in children. Leukemic cells from birth may require more specific and less intensive drugs than adult patients.


At this point, I feel that it is important to point out the difference between "stem cells" and what is popularly termed "cancer stem cells".

Stem cells are cells which exist in the body and are responsible for continuous maintenance of the body and a controlled replacement of our cells and tissues. The stem cells are known to be "relatively immortal" (ie they live a far longer lifespan than our normal cells, which may die after 7-90days) and are key to our existence and survival of our blood and immune systems etc.

Cancer stem cells however, are like other cancers -cells gone wrong- except that the cell that has gone wrong is the stem cell. Hence, the cancer stem cell does not make other tissues and does not replace cells like it should. It merely makes more of itself, which isn't useful under the normal circumstances.

So, a pertinent question to ask is how do you know a stem cell from a cancer stem cell? Well, Prof Enver believes that there is a lot of talk about "markers" for stem cells, but there is no doubt that these markers have a long way to go in being defined and that the best way to know is to conduct functional studies (ie, to see how the cells really work in real life).


REAL LIFE SCENARIO

A pair of very beautiful twin girls from Bromley a city in Kent, were the subjects of the study. According to the news story, which was reported in January this year, Olivia Murphy developed acute lymphoblastic leukemia (ALL) when she was 2 years old, while her twin sister Isabella remained healthy. I'm not exactly sure how the case came to Prof. Enver's attention at the MRC (I wanted to ask him but didn't get a chance) but he and his group ended up researching why one of the twins developed the disease while the other remained healthy. Prof. Enver's team elucidated that both twins carried a gene that pre-disposes them to developing the ALL, but while Isabella only had one hit to her gene, Olivia had two hits which resulted in cancer development (cancer usually results from several mutations to certain genes which allow the cells to grow uncontrollably).

They proved to be the perfect research subjects to understand if genetics had a pivotal role in the stem cells, which could already be susceptible to chance changes after birth. The aim of the research, was to discover where the point of change was that resulted in the cancer, and whether it would be possible to design a method to protect the susceptible genes (prevention) or necessary drugs which would target the cancer cells.

There was a more detailed write up which describes how the twin's parents brought Olivia in for fever which the doctors had then thought was tonisilitis. The parents insisted on a blood test and were given the ALL diagnosis. Fortunately, Olivia's cancer responded well to the chemotherapy and was a success, but not without side effects.

The chemotherapy was so strong that her immune system was damaged and she suffered six attacks of shingles (chicken pox relative) which infected her eye and blinded it. In the course of research, Prof. Enver's team took regular samples of both the girls' blood and the doctors will screen Isabella regularly to monitor any signs of the 'second hit'.


OPTIMISM FOR TARGETING PRE-CANCER CELLS

According to Prof. Enver, as the total cancer relies on less than one per cent of the cancer generating cells to maintain the disease, this offers a unique opportunity to develop better drugs to kill off this one per cent of cells. He was quoted saying that there could be a day where the prevention of leukemia would be possible as the pre-leukemia cells could be eliminated at the source, potentially curing 90% of the cases detected.

However, no medical procedure is risk free and the strong chemotherapy may result in the death of 1-2% of cases treated. And for those couples with identical twins, you might like to know that nine out of ten children who have an identical twin with leukemia do not develop the disease.

That means that Isabella's chances of staying cancer free remains pretty high. :)

Blogging Live from Singapore at the UK-Singapore Stem Cell Symposium

Its been a long time since I sat in a room full of developmental biologists discussing the intricate biochemical pathways -some discovered and debated heatedly- and listened to the fundamental scientific research performed in the UK.

Organized by A*STAR’s Singapore Stem Cell Consortium and the British High Commission at Singapore’s Biopolis, it was another event which made evident Singapore’s financial commitment to establishing a scientific research base through educating its PhD students and motivating local researchers to aspire to international knowledge standards. Since I did spend a few years in a research position in Singapore, it is only right that I promote their efforts in scientific education.

15 scientists (of which 7 were Professors and researchers from their respective departments) from the Universities of Cardiff, Cambridge, UCL, Sheffield and Edinburgh presented a thirty-five minute summary of their work involving stem cell pathways derived from embryonic cell lines and cancer cells.

All the presentations were very technical (as they should be) and involved the investigation of signaling pathways in the cell.

For those who are less scientifically inclined, signaling pathway research, in plain language is finding out how a cell talks to another cell, and how each of the cells respond in body language according to what is said. Imagine that a cell is itself made up of many components (kind of like organs within your body) and these components need to synchronize in order to regulate and make the cell what it is, or what it is to become. In this case, the researchers were trying to find out which factors affect the embryonic stem cells and make them change or “differentiate” into a specialized cell type.

As always in basic scientific research, as long as governments don’t run dry on funding, scientists will always have work to do because we are still a long way off understanding how our cells talk to each other, and most importantly how to control unnecessary conversations which may spark off a chain of unwanted reactions.

You can find the list of speakers and topics here, and for the sake of brevity and also without having to go into too much basic cell biology, I’m going to give you an outline of a few of the talks which I find easier to explain and are relevant to the faithful readers of this blog. I've chosen 4 presentations (Prof. Tariq Enver, Dr. Phil Jones, Dr. James Hui and Prof. Pete Coffey) to share with you and you'll find them in the ensuing entries.

Part 4: Bangkok Conference on Stem Cell Therapy for the Failing Heart

MERRY CHRISTMAS EVERYONE!
Thought I'd share with you how we've decorated the office for the season. After a short break yesterday and a hearty dinner, I'm back to the blog...

Let's plunge right into it, the review of the last talk by a Tv representative. The CEO of Tv, Dr. Valentin Fulga didn't give away too much of the company's information or much on himself, except to review the cases done to date and also that he had some experience with the FDA and planned on getting approvals relatively soon. Much of the information he had was already mentioned in other talks and he used his time to credit them for their participation and active work.

THE QUESTION

I promised an answer to DTR's question and essentially I did pose this question at the very end of the symposium to Dr. Valentin Fulga, the CEO of Tv. Firstly, I commended him on successfully having Tv's stem cell technology effectively marketed the treatment to 180 patients to date. Logistics and coordination in itself is a real feat (flying the patient to Bangkok, flying the cells to Israel and back to Bangkok- wouldn't like to know their costs..), not to mention marketing the concept to doctors, hospitals and the patients from all over America. I noted also that almost all the patients were treated in Thailand, and curiously, none in Israel. I asked him why was this not the case as most lab services are derived out of its own community's requirements initially and then to serve a greater regional need.

THE ANSWER

He sort of woffled on for a few minutes and basically said that they were in the process of doing so but didn't really answer my question. I tried to assist by asking if perhaps it was a political issue in Israel that prevented them from doing any clinical work there; and his answer to that was that if there was a political problem he certainly didn't know about it as he hadn't been there in the last 2 months. Essentially, as Dr. Itescu pointed out to me later, there may similarly be many questions and queries on the validity of the work by Tv posed by Israeli doctors which is why they've taken their work to wherever they can.

I also spoke briefly to the president of their company in Thailand and the Asian region, a young trendy thirtysomething who goes by the name of Jimmy, he eluded to a fairly complex ownership structure of subsidiary companies and I wasn't entirely sure how he ended up in this business.

Anyway, since the cells are autologous and the treatments don't seem to be more risky than standard heart bypass procedures, I wish them well in their business as they may set an interesting price and model to shape how people in the US perceive stem cell therapy... preferably, with a vacation in Amazing Thailand. :)


StemLife also offers stem cell harvesting, processing and therapeutic services with renown Malaysian doctors for patients with heart failure and ischemic heart disease. If you're interested to learn how your stem cells can help your failing heart, please feel free to call us at +603 2163 8800 during office hours or ask your doctor to contact us at info@stemlife.com.


ps. If you missed the other parts of the conference entries, click on the label for "conference"

Part 2: Bangkok Conference on Stem Cell Therapy for the Failing Heart

Thanks DTR, for prompting me to write another entry on the heart conference I attended in Bangkok. These next few entries will hopefully answer your questions, which are pretty much my own as well.

As the main sponsor of the conference, alongside Bangkok Heart Hospital, it was Theravitae's aim to showcase their technology and data to impress doctors from all over the world. Notably, the speeches were delivered by three company respresentatives. Namely Yael Porat (who is the chief scientist at Theravitae's lab in Israel), Dr. Valentin Fulga (CEO of Theravitae Ltd in Israel and Bangkok) and one of the founders by the name of Don Margolis.


Review of Theravitae talk by Yael Porat, Neiss Ziona, Israel

Yael Porat's talk was more "technically" based, giving some simple parameters by which they qualified their work. Essentially, they take a bag of blood (250 ml) from a potential heart patient, fly it over to Israel and leave it in Yael Porat's lab. In simple terms, she plates in out into cell culture flasks and lets the cells known as ACP's (angiogenic circulating progenitors) grow in the presence of growth factors such as EGF, VEGF, IGF and b-FGF. She stresses that no animal serum is used, only patient's autologous serum and some heparin (as an anti-coagulating factor).

After growing the cells several rounds in a GMP/ clean room type facility and achieving as much growth as they can without damaging the cell line, Yael resuspends the cells in medium (not sure what medium it is but it looks like serum), packages the cells in syringes and sends it to the hospital in sterile, bubble wrapped pouches and shhipped at 2-8 degrees Celsius. This final product is known as Vescell and is applied to the patient either via angioplasty or by direct intramyocardial injection.

She couldn't give much away in terms of information apart from showing how they labelled the cells and assuring the audience that the lab in Israel was par excellence. Her slides were mostly text based with just one picture of a biosafety cabinet in a clean room and the cells in syringes and a few staining images. The questions which followed her talk mostly pertained to the manipulation of the cells and its logistics. Manipulation* wise, it seemed like pretty standard cell culture techniques without much selection (although without further disclosure from them, I really wouldn't be able to confirm this) but in the US, FDA does not permit the use of any manipulated cells at this time.


QUESTIONS & ANSWERS


Dr. Doris Taylor asked about the logistics of the cells which have to travel from Bangkok to Israel and back, how would the cells be transported and how would they ensure quality without deterioration or even that they remained the same cells during the journey?

PACKAGING:
In a cooler bag with temperature logger throughout journey to ensure the cells are kept between 2-8 degrees C.

CELL IDENTIFICATION:
The answer that Yael gave was that Theravitae would check the cell numbers and their identity prior to shipment, but there would not be any necessary checking at the hospital when the cells arrive. (ie assumption that cells stay the same)

TRANSPORT:
Next flight out policy, and they have already checked how the cells in the collected blood (at the beginning) can still be viably used after 24 hours as Yael used to work on old/ expiring bags of blood obtained from the blood bank. As for bringing the cells back to the hospital, she says that the cells have to be packaged right and be shipped to the site within 24 hours by special courier.

Next was a question by Dr. Sujit Banyatpiyaphod, cardiac surgeon from Bangkok Heart Hospital. He asked if the cells could be frozen down? Reason being that some of the heart patients were in critical condition and if the patient needs to wait another 2-3 days after the cells arrive for the injection procedure, would the cells still be ok to use or can it be kept frozen for application at a later date.

Yael replied with a NO, the cells cannot currently be frozen down although they are trying to work on it. Right now, if the patient is unable to use the cells, then she would prefer if the doctor collected another round of blood and send it over to her again for culturing so that it is prepared fresh.


PRACTICAL & LIMITING CONSIDERATIONS


It seems to me that there are some practical considerations to this sort of cell therapy where time limitations and cell viability all play a sizeable role in the economic costs to patient, planning costs to the doctor and hospital. One thing Yael didn't volunteer, was whether this situation has arisen before and whether there is a company guarantee for another round due to unexpected circumstances.

Even if Theravitae builds a lab in Bangkok and shortens the logistics time, it is clear from this they will still need to overcome the issue of storage or of affordable 2nd time therapies. The way to understand this is to really understand cellular biology- cells are alive, metabolism keeps going and prolonged exposure to a different or manipulated environment has its own way of changing cellular fate. Obtaining fresh blood from the patient may not be difficult, but re-culturing them in time for the procedure (if its urgent) is a present challenge.


I'll be writing about what the CEO said in the next entry- and answering DTR's question posed in the last blog. :)


*Manipulation in this context means the alteration of the cells' environment, or selecting for certain cells in a mixture, or the addition of factors which may induce changes in the cell's composition or identity.

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.

StemLife attends Cord Blood Transplantation Conference in Biopolis, Singapore (1)

The StemLife team supported the organizers and attended the "Short course on Cord Blood Transplantation" meeting held today in Singapore's most prestigious research facility Biopolis (equivalent to the NIH for the lion city). Co-organized by Johns Hopkins, National University Hospital, Singapore Cord Blood Bank (SCBB) and the local Society of Haematology, it was quite a successful turnout of speakers and attendees who provided a lively audience.

Guest speakers today included Prof. Eliane Gluckman (1st cord blood stem cell transplanter), Prof. EJ Schpall (MD Anderson, FACT-Netcord accreditation), Prof. Takahashi of Tokyo University, Prof. CK Li from Prince of Wales Hospital Hong Kong, Prof. Ian McNeice, Johns Hopkins Singapore. Local speakers included Singapore's well known haem-oncologists Dr. Tan Ah Moy, Dr. Tan Poh Lin and Dr. William Hwang (now medical director of SCBB) and Dr. Michael Choi of Viacell Singapore.

Attendees included a collection of representatives of cord blood banks (largest stem cell company turnout from StemLife!), doctors from local hospitals and interested physicians and some students.

The seminars revolved largely around the results of cord blood stem cell transplantation since the first one performed by Prof. Gluckman, it is quite clear that the process of transplantation has been refined and improved tremendously. The data from her talk showed that unrelated donor cord blood stem cell transplants were as good as or better than proceeding with unmatched, unrelated bone marrow transplants. Nucleated cell number is still used as the transplant indicator as the correlation with CD34+ cells in cord blood was still tenuous, and the Gluckman recommendation was that at least 2x10e7 NC/Kg at infusion must be obtained for a greater chance of success in malignant diseases (StemLife derives its cut-off value from this recommendation). A member of a pharmaceutical group from India raised the question if she would use a unit which was contaminated with bacteria, given that it could be treated with antibiotics. Prof. Gluckman answered that she would not accept nor use the unit for fear of an adverse and unpredictable effect, which could lead to the death of the patient.

Also discussed were new protocols in cord blood transplantation using double bags of cord blood stem cells which should be as closely matched as possible and have shown promising results although the procedure still requires refinement. Prof. Gluckman's conclusion was that "cord blood is a unique resource for transplantation, regenerative medicine and scientific research, and for this purpose, there is an increasing need for the number of quality units stored".

Prof. EJ Schpall's talk centred largely on FACT-Netcord Accreditation, which is probably most applicable to the public banks who wish to trade their units internationally. She was quite clear on the fact that "public banks" around the world were in competition to "sell" the most number of units for transplantation (USD 21,000 per unit). A high barrier of entry is created through complying with standards and required protocols. She also stressed that FACT only accepts banks storing in cryobags and do not accept vials or any other form of storage.

This criteria would immediately eliminate banks storing their units in vials from participating in FACT accreditation or wishing to join Netcord in the future.