A cure for Type 1 Diabetes - with Peripheral Blood Stem Cells

While researchers battle it out trying to prove the supremacy of various stem cell types (embryonic, mesenchymal etc.), it is worth remembering that so far, blood derived stem cells have been used for a great variety of cures (if you know of any human that has been actually cured with an embryonic stem cell, please let us know).

During my nocturnal, pre-bedtime web surfing (I suspect that I'm not the only one with this habit...), I came across a video describing the way blood stem cells* obtained from the same patient was used to provide a successful treatment for patients with recently diagnosed type 1 diabetes. This work isn't that new -I blogged about it back in 2007- but it is a very significant milestone in the history of stem cell transplantation.

Dr. Richard Burt's work is really quite demonstrative of how our blood and immune system plays a very significant role in whether our tissues and organs break down- and where stem cells obtained non-invasively from the same patient's own blood stream- have a clear role to play. I have yet to meet Dr. Burt in person but know him through his work and this video is the first I've seen of him providing a very clear insight into the trial that he is conducting. He highlights that 14 out of 15 patients were successful in treatment and this is an excellent base number to build on for the next clinical trial.

Dr. Burt published his work in the well renown and respected Journal of American Medical Assocation (JAMA), but instead of reading it I thought this video version sums it up really nicely for the non-medical and patient community.



If watching the video makes you more interested in reading the journal article, click on this link Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus.


*StemLife offers individuals the opportunity to bank their babies' cord blood or stem cells from adult blood for therapeutic use.

Autologous-OWN-Stem Cell Infusion And Hyperbaric Oxygen Treatment Improve Islet Function In Diabetes

A study to determine if patients with type 2 diabetes can benefit from a combination of autologous (patient OWN self-donated) stem cell infusions (ASC) and hyperbaric (above the normal air pressure of ) oxygen treatment (HBO) before and after ASC has found "significant benefits" in terms of "improvements in glycemic control" along with "reduced insulin requirements."

The combination therapy could decrease type 2 diabetes morbidity and mortality, said the authors, who published their study results in a recent issue of Cell Transplantation (Vol. 17 No.12).

"Autologous stem cell therapies are an emerging set of therapies with promising results and low side effects profiles," said corresponding co-author Esteban Estrada, MD, of Stem Cell Argentina.

"In addition, hyperbaric oxygen therapy, used primarily in the treatment of carbon monoxide poisoning, air embolism suffered by divers, and as an enhancement to wound healing, has been shown to increase stem cell mobilization and the release of endothelial progenitor cells via a nitric oxide-dependent mechanism."

The clinical trial evaluated the safety of ASC-HBO combination treatment in 25 patients with type 2 diabetes.

According to the researchers, it is well known that with type 2 diabetes, there is an ongoing inflammation of the pancreas. Their hypothesis suggested that mobilizing stem cells would cause the growth of blood vessels (angiogenesis) and release factors that would result in the local differentiation of progenitor cells with a resulting anti-inflammatory effect. Diabetes, they added, has been shown to impair progenitor cell mobilization, a problem that local stem cell infusion could remedy.

Once more, the effect of the hyperbaric oxygen therapy, they hypothesized, would be to increase stem cell mobilization in such a way as "to target more than one crucial reparative step" to counteract the chronic injury that attack the endothelial progenitor cells and the islet cells.

"Overall, our results show that a close follow-up with intensive diabetic management alone could not be the only cause of the positive, progressive and consistent outcomes we obtained in this trial over one year of follow-up," said Dr. Estrada.

"A decade ago, research had explored stem cell transplantation and hyperbaric oxygen therapy as stand alone treatments. This study highlights the potential benefits of using an unusual combination therapy to treat diabetes" said Dr. Cesar V Borlongan, Associate Editor of Cell Transplantation and Professor at the University of South Florida College of Medicine.


References

Estrada, Esteban J.; Valacchi, Fabian; Nicora, Eduardo; Brieva, Sergio; Esteve, Claudio; Echevarria, Laura; Froud, Tatiana; Bernetti, Karina; Cayetano, Shari Messinger; Velazquez, Omaida; Alejandro, Rodolfo; Ricordi, Camillo. Combined Treatment of Intrapancreatic Autologous Bone Marrow Stem Cells and Hyperbaric Oxygen in Type 2 Diabetes Mellitus. Cell Transplantation 2008; 17 (12): 1295-1304.

Singapore advertises Cord Blood Stem Cell Banking (Part 2)

A Cordlife ad was timed right after the appearance of the Singapore Cord Blood Bank's news article - and that wasn't a coincidence.



In fact this latest ad was a masterful stroke of PR execution, citing rates of stem cell usage from the SCBB's own article and adding on the other applications worldwide. It highlights what families ought to store their own babies stem cells for their own use and advocates that private cord blood banking ensures 100% accessibility to your own banked cells.


If you can't see the facts and figures in the picture above here's the wording on the left:

Incidence rate of stem cell treatable diseases:

6 people are diagnosed with blood related diseases in Singapore every day
2 of the top 10 cancers afflicting Singaporeans are Lymphoma and Leukemia
1 in 500 babies are diagnosed with Cerebral Palsy
2 children are diagnosed with Type 1 diabetes in Singapore every month
80 diseases are now treatable using cord blood stem cells and possibly more in the future.

Chances of using stem cells:

1 in 217 chance that a person may need cord blood stem cells for treatment in their lifetime
80 cord blood units were released for transplants and therapeutic applications by Cordlife.

Higher chance of finding a match within the patient's family:

70% of cord blood transplants by Cord Blood Registry were from siblings. 30% was for self use.
75% chance of a sibling match
25% chance of a 100% match between siblings. A perfect match is required for bone marrow transplants but not in cord blood transplants.
$26,000 is the minimum cost of buying back a donated cord blood unit if it is still in storage.

Availability of stem cells:
50% of all donations to a public cord blood bank are normally discarded for various reasons
100% - your accessibility to your privately stored cord blood stem cells.



All true of course, and I've always wondered this: Singapore's birth rate is at thirty to forty thousand per year and it's conceivable that there may be a time when every Singaporean has his or her cord blood stem cells banked in the future. Given Singapore's small population, its probably the best place imagining that this could happen, a very accessible and heterogenous database which could be leveraged for treatment and if consented, research for autologous regenerative purposes.


Now that would be really cool.


** Unfortunately the online version of this article isn't the full version that was published in print.


Malaysian Medical Advertising Regulations prohibits any form of advertising using terms ranging from "treatment" to "Thalassemia" so it is virtually impossible for us to advertise as our neighbors did (all brochures and the stem cell organization are required to be separately licensed by the Ministry of Health, so make sure the stem cell bank you're talking to has all the documented approvals and are operating within legal guidelines).

However, since all of it was factual and cited from peer-reviewed journals and both local and international news articles, its good to share these statistics with our patient base here too.


More information on StemLife's stem cell banking services can be found at www.StemLife.com

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Singapore Advertises Cord Blood Stem Cell Banking (Part 1)

Last week in the Singapore Straits Times, there were two snippets about cord blood stem cell banking. The first one was a news piece on the Singapore public cord blood bank (entitled Cord Blood Bank has saved 21 lives**) which was campaigning for an increase in units (arguably an ad in itself). The other snippet was an ad by a local private Singapore Cord Blood Bank Cordlife. The ad appeared 2 days after the news article and I don't think its a coincidence to keep the conversation and interest in Singaporean's minds.

The first article from the Singapore Cord Blood Bank at a press conference reveals quite a lot about what its like to be an operator of a public bank:

How many cord blood stem cell units have been released and where have they gone?

"In the 3 years it has been open, the Singapore Cord Blood Bank has saved 21 lives - here and overseas... a 22nd donation was winging its way over to France"

"Of the 21 recipients, 12 were patients here while the other nine were ethnic Asians in Europe and Malaysia."

Comment: 21 cord blood units utilized in transplantation is very respectable for a small bank. Financially, at a purchase price of SGD 26,000 per unit in Singapore, the SCBB would have generated SGD 312,000 in revenue for the 12 Singaporean patients and another approximately SGD 320,000 from the 9 overseas patients (assumption is that these patients came through the NMDP network and paid the standard price). That would bring the SCBB's total revenue to SGD 632,000 or slightly more than this.


How many Singaporeans have donated cord blood and how many of those have been successfully banked?

"The repository has been able to bank about half of the 9,000 donations so far. Donations sometimes do not yield enough stem cells to be viable*."

Comment: The yield of 50% is very much in line with what I've heard from other public cord blood banks. However the article doesn't explain that units are discarded due to bacterial / viral contamination (let's not forget that vaginal flora and fauna can be quite substantial) and that the cord blood bank sets its own guidelines as to the volume and/ or cell count required at the beginning before they proceed to process the unit.

As a guide, at the time of receipt of the cord blood unit, most public cord blood banks insist on a minimum volume of 100 mls or total cell counts exceeding 1 billion. The rationale for this is that the cord blood unit needs to be at a level high enough to treat an adult (including caucasian weight & bigger sized asians), otherwise its not worth keeping (bearing in mind that this inventory can and most certainly will take years to clear). *Thus the term "viable" in the article refers to the unit's chances of being used.

Targets for the Singapore Cord Blood Bank?

"An earlier target of banking 10,000 samples by next year has been extended to 2013 said Mr. Sobak (SCBB's CEO and COO of SingHealth), since its been harder to get good-quality donations."

Comment: 10,000 units in the tank is an ambitious target but let's consider the following points:

1) The SCBB is based in the KK Women's and Children's Hospital, which alone delivers the vast majority of Singaporean babies has handled almost 40,000 babies at its peak, but more likely in the range of fifteen to twenty thousand now.

If the SCBB were able to collect all of the cord blood units from all the babies delivered there per year, without approaching any other hospitals (and discounting the 50%) the SCBB would have had about twenty thousand or so units by now. But, that would mean that they would have been working at a pace of 20 units per day seven days a week, all year round for 3 years. Hence the limitation of time, processing space and cost all plays a part in the operational capacity. [4 years more for 5000 units]

2) Cordlife, the first local Singaporean private cord blood bank started in 2001 only recently achieved 13,000 units in 2008 (announced in an ad) and claim only a 1% contamination rate, which means that they store almost every unit they receive. So repositories take a long time to build. [7 years for 13,000 units]

3) StemLife achieved 10,000 units in 2006, about 4 years after operational commencement (I assure you, not without toil).


Another target mentioned by the CEO was 30 transplants for the financial year 2009. I find this to be an interesting target, as I suspect it greatly depend on whether the requests just happen to match the units in the tank? Or perhaps it is now possible to analyze the recipient population and to try to identify the relevant donors to collect the cord blood from.

Anyway, getting back to the financial year for SCBB, I suppose the financial target would be in excess of SGD 1 million in revenue - if they manage to sell the inventory overseas. It is a business after all.


What are the likelihoods of use?

"At least six people are diagnosed daily in Singapore with different types of blood-related diseases said the bank's medical director William Hwang."

"Many of these patients will require a blood stem cell transplant to survive"

"With these samples and those fom banks worldwide, the odds of local patients finding a match is about 10-20%"


OK, quick back of the envelope calculation here. 6 people diagnosed daily in Singapore with a blood related disorder, ie 2000+ people. Let's say 50% will require a transplant at some stage, so let's bring the figure to about 1000 people needing a transplant.

And since only 10-20% will be able to find a match from all available units locally and internationally, ie 100-200 people will get their stem cell treatment... and the rest will have to wait.

The IMPORTANCE of YOUR FAMILY'S STEM CELLS

Haemopoietic stem cell transplantation for children in Australia and New Zealand, 1998–2006:a report on behalf of the Australasian Bone Marrow Transplant Recipient Registry and the Australian and New Zealand Children’s Haematology Oncology Group.

This above study is an important milestone epidemiological study in CHILDREN published in the Medical Journal of Australia in February 2009. It gives us invaluable information and insight on the source of stem cells used (from bone marrow, peripheral blood or cord blood), their origin (autologous: own; related allogeneic: matched siblings; unrelated allogeneic: matched strangers) and on the indications for which a bone marrow transplantation has been performed. Moreover, it studies the important aspect of Transplant Related Mortality (TRM). Few of us actually have insight in those issues and understanding them will aid in deciding whether to keep your own stem cells or not.

Let's have a look!

Over a period of 9 years (1998-2006) 1,259 BMTs were performed in children in Australia and New Zealand, of which 41% were autologous (used the child's own stem cells from bone marrow or peripheral blood) while 59% were allogeneic (someone else's stem cells). Of the latter 40% were from a matched sibling (23.6% of the total) and 60% from matched strangers. That brings the total number of children ultimately finding stem cells from themselves or within their immediate family up to 65% while the remaining 35% had to depend on matched strangers to donate or on donated cord blood. It means that at the end of the day when a child was ill and in need of stem cells for BMT, then those were found in 65% of the cases from the child or the immediate family. More important is that the stem cells used were bone marrow or peripheral blood stem cells and that means that in that perilous period of a family's and a child's life an extra burden in collecting stem cells from the bone marrow or peripheral blood is added on top of all stress that is already evident. One can also speculate how this additional psychological stress and wait may impact on disease progression. If those families had been informed about cord blood stem cells and had kept their children's cord blood stem cells then those little frozen bags would have been stored and waiting to be used at any given time! Furthermore, the importance of using your own or those of a matched immediate relative is reflected in the TRM; Transplant Related Mortality is 22-28% when one receives a matched stranger's stem cells and only 5-7% if one receives their own or a matched sibling's stem cells.

The other important issue is that the matched stranger stem cells come nowadays more from donated cord blood stem cells than bone marrow/peripheral blood. In the latest years more than half, almost 2/3, come from donated cord blood and subsequently since cord blood stem cells are immunologically naïve and cause 30% less rejections, more mismatched transplants have been performed. One can speculate if this is the reason for the difference in Transplant Related Mortality that is higher in mismatched stem cells from strangers. So, if one would not keep for own use one should definitely donate for public use!

In the words of the authors of the study “Autologous BMT has an important role in a range of childhood cancers, including neuroblastoma, medulloblastoma, Ewing sarcoma/PNET, Hodgkin lymphoma and non-Hodgkin lymphoma” while “allogeneic (matched siblings or strangers) transplantation is most frequently offered to children with high-risk and relapsed leukaemias, myelodysplastic syndromes, aplastic anaemia, congenital bone marrow failure syndromes, thalassaemia major, sickle cell anaemia and various inborn errors of metabolism”.

The results of this study are similar to a previous one published in the Biology of Blood and Marrow Transplantation in 2007, entitled “Haematopoietic Stem Cell Transplantation in Australia and New Zealand, 1992-2004”. In this study that encompasses all transplantations in Australia and New Zealand both in adults and children, the same trend is evident and even more pronounced. That is, when you need stem cells you find them in you or in your immediate family! In2004 alone, 68% of the patients used their own stem cells (889/1,313) while another 19% received stem cells from matched siblings and only 13% managed to find stem cells from matched strangers. That means that a total of 87% found the needed stem cells in themselves or within the immediate family! Importantly, Transplant Related Mortality was 8.1% for stem cells from strangers compared 1.1% for own stem cells! One can also in the adult cases speculate how the effect of the additional psychological stress of stem cell collection and/or wait to find stem cells from strangers may impact on disease progression. If those families had kept their own peripheral blood stem cells then those little frozen bags would then have been stored and waiting to be used at any given time!

Cord blood stem cells and peripheral blood stem cells have an immense importance be it for a family's own use or for complete strangers where anyone can offer the hope of life. Regardless the use or the intention, those stem cells must be kept for their purpose to be fulfilled! Do not let them go wasted!

References

1. Moore AS, Shaw PJ, Hallahan AR, Carter TL, Kilo T, Nivison-Smith I, O'Brien TA, 
Tapp H, Teague L, Wilson SR, Tiedemann K. Haemopoietic stem cell transplantation
for children in Australia and New Zealand, 1998-2006: a report on behalf of the
Australasian Bone Marrow Transplant Recipient Registry and the Australian and
New Zealand Children's Haematology Oncology Group. Med J Aust 2009; 190(3): 121-5  

2. Nivison-Smith I, Bradstock KF, Dodds AJ, Hawkins PA, Ma DD, Moore JJ,
Simpson JM, Szer J.Hematopoietic stem cell transplantation in Australia and New Zealand,
1992-2004. Biol Blood Marrow Transplant 2007; 13(8): 905-12 

Autologous PBSC bone marrow transplantation for MS

Fantastic NEWS for MS patients. New hope in the horizon with OWN Peripheral Blood Stem Cells the way StemLife companies around SE Asia have been collecting and storing for the past 9 years. This novel phase US II/III study (click on the title to see the study) confirms what European scientists have been investigating in the past few years with dr Fassas in Northern Greece as one of them. So this study provides one more proof that in Patients with MS, their OWN Stem Cells can be their chance to live a normal life again!

If you wish a comprehensive list on MS, a presentation in pdf form is available after emailing to info@thaistemlife.co.th