Newsletter - December 2012
Eggs, exactly when you want them
It seems that everything in our world is changing. It is a sunny day, the temperature outside is 80°F in December in America's heartland, a nine-year-old girl is visiting the doctor because she is developing breasts, and I had a meeting with a 54-year-old woman who wants to have a child. It seems that the physical world and the biological world are transforming almost before our eyes. Over the last hundred years we have seen the life expectancy of a woman double, going from 40 years to over 80 years. As a result our society is changing. Our young girls grow up and dream of having "it all": an education, a satisfying career, and a family exactly when they are ready. Unfortunately some things don't change quite as quickly.
The reality is that a newborn female is born with approximately 2,000,000 oocytes or immature eggs. The moment she is born, the eggs begin to die slowly, and by the time she reaches puberty, she is down to approximately 400,000 primordial eggs. During a woman's early fertile years it is believed that these eggs begin to wake up in groups of about 800 to 1000 eggs at a time and start a 60 to 70 day journey which will end with only one or two of these eggs reaching maturity - the second stage of division/meiosis where they are ready to be fertilized. Once the eggs "wake up" they start to die off even faster, to allow for the selection of the "winning egg".
A woman's egg supply dwindles predictably over the years... so that by the time a woman reaches age 30, there is roughly a 10% chance that she would fall into the category of "diminished ovarian reserve", and a 25% chance that her egg supply would be in deep trouble by age 35. Experts believe that no more than 20 or 30% of women will be able to conceive a child on their own after age 40, no matter how successful she's been in the past at doing so. There are many days where I think to myself, after I met a young couple who are dealing with a significantly low egg supply, that my reproductive medicine colleagues and I are derelict in our duties. We should have road signs put up, the way the American Cancer Society does begging people to stop smoking. Our signs should read "get pregnant before you're 30". My colleagues and I would be thrown into Political Correctness Prison.
Well, science and medicine are fighting back. Today we can identify women who have a low egg reserve using a variety of tests. At my program, the Fertility Partnership, it is called the Fertility Profile. Basically it is an opportunity for a 30-year-old woman to check and see what is the likelihood that she will have an issue in the near future.
In October 2012, the American Society of Reproductive Medicine (ASRM) announced that they had reviewed all the literature and have deemed the freezing of human eggs to be safe and just as effective as freezing human embryos. Oocyte freezing is no longer considered "experimental". Advances such as "vitrification", a technique where the eggs are frozen very quickly as opposed to a slow process, have dramatically improved the science of freezing and thawing human eggs. The change in the status of oocyte freezing from experimental to routine now opens the way to any and all fertility programs to offer a woman the opportunity to freeze her eggs when she is young so that she may have them when she wants them.
Imagine a 30-something year old woman who is working on completing her PhD, or climbing the corporate ladder, or just still searching for "Mr. Right". She can reliably store some of her eggs now so that she can start her family later when the time is right. Think of all the pressure that is now removed from that person. I have spoken to so many women that seem to be gnawed away by the desperation that their biological clock has ticked away too long. Our technology is catching up to our changing society. But this is only the beginning. There are many more advances coming.
Parent's Guide 2012 in Review
My daughters and I bring you "Season's Greetings" from the Parent's Guide to Cord Blood Foundation. In the United States, where we are based, many people are celebrating the Jewish holiday of Chanukah and the Christian Holiday of Christmas. Elsewhere in the world, the peak holiday season has passed for Muslims who observe Ramadan and Hindus who celebrate Diwali. Running the Parent's Guide keeps us aware of everyone's Holidays because we are an international outreach organization.
We recently reviewed some of the demographics of our outreach: Only 65% of the readers of our website are in the United Sates. Our second biggest source of readers is India, which edged out Canada for the number two spot in 2010. Most readers, 89%, rely on English as their language, despite the ability to use a Google translate button for our web pages. About 70% of our readers are new each month, typically expectant parents who have decided they need to find out why their baby's cord blood is important, and what are their options?
India is currently the world's biggest market for family cord blood banks. With a birthrate of 27 million per year, much higher than the US birthrate of 4 million per year, India is projected to overtake China and be the world's most populous country by 2030. At the Parent's Guide, we consider improved outreach to India to be one of our top priorities. We need more connections to members of the cord blood industry in India, more complete descriptions of banks and clinical trials, and new partnerships to distribute educational materials. We also hope that in the near future there will be more effort to develop a public network in India to collect cord blood donations for transplant patients.
Another demographic shift in today's society is the changing use of technology. Most people don't pay any attention to what type of software their computer uses to browse the internet, but we are forced to pay attention to differences in the way our website displays in different web browsers. The dominant browser is Microsoft's Internet Explorer in the US, UK, and China. However, Google's Chrome dominates in India and much of the EU.
Even in the developing world, today almost everyone has a mobile phone, and more and more people are using smart phones that can connect to the internet. The analytics data from our web server suggests that perhaps a third of our readers are using mobile apps to browse the internet. Any organization that wants to conduct outreach to young people today must have a web site that is phone-friendly. We consider it a priority to develop our website in that direction during 2013 and thereafter.
We wish all our readers a healthy, happy, and prosperous year 2013 on the solar calendar, and soon the Chinese Year of the Snake.
Banking Stem Cells From Umbilical Cord Tissue For Future Regenerative Medicine Applications
Umbilical cord blood is a great source of young blood-forming stem cells (called hematopoietic stem cells or HSCs). Currently, stem cells from cord blood are used in the treatment of a host of blood-related diseases. However, a major drawback of cord blood transplants is the limited volume of blood that can be collected from a single umbilical cord. Consequently, a limited number of stem cells can be derived from a single cord blood collection.
Transplants are more successful with a higher cell dose, hence numerous methods are currently under investigation to increase the efficiency of cord blood transplants, including ex vivo expansion of the hematopoietic stem cells before transplant, increasing the homing of hematopoietic stem cells to the patient's bone marrow, direct injections into the patient's femoral bone, and transplants with multiple cord blood units. A more straightforward method is to utilize another stem cell population - mesenchymal stem cells (MSCs) - for co-transplantation with a cord blood unit.
MSCs are a natural choice for co-transplantation with HSCs from cord blood, because MSCs are protein factories that produce growth factors and cytokines that signal and cue the HSCs to maintain proper blood and immune function. Due to this complex, symbiotic relationship, it has recently been found that when MSCs are co-transplanted together with HSCs, they enhance the stem cell engraftment up to 6-fold [1,2].
In adults, HSCs and MSCs are found together within bone marrow and the two populations work in concert to maintain blood function. But while infant cord blood is a rich source of HSCs, it is a poor source of MSCs. At birth, the richest source of MSCs is "after birth" tissue - especially within the Wharton's Jelly of the umbilical cord tissue.
The MSCs in umbilical cord tissue can easily be harvested and banked alongside umbilical cord blood. Currently, there are two main methods to bank MSCs from the cord tissue. The first is to simply chop the cord into small pieces and cryopreserve the minced tissue, with the MSCs inside the tissue, for later processing. The second is to thoroughly process the tissue upfront so that the MSCs are extracted and can be saved in "treatment ready" form.
Our company, AuxoCell, has developed a method to extract MSCs from cord tissue by first mechanically mincing the tissue, followed by an enzymatic digestion to "melt" away the tissue, while releasing the native MSCs. The released MSCs can be easily collected and cryopreserved as a single cell suspension, much like stem cells from cord blood.
The pros and cons of extracting MSC before or after freezing involve many factors, including: time, cost, cell potency, and cell therapy regulations. Although both methods render MSC products suitable for cell therapy, they are quite different. The final MSCs derived from frozen tissue are biologically different than the native MSCs collected prior to freezing.
The advantage to the bank of freezing tissue without extracting cells is that this method is simple, quick, and inexpensive. However, should the client family wish to use the MSCs in that tissue for therapy, it would require that the tissue be thawed, the surviving MSCs extracted, and those MSCs would have to be cultured in the lab to grow a sufficient population for therapy. This process would take weeks, run up costs, and result in a final cell population that the US FDA would regulate as a drug.
The advantage of extracting cells before freezing is that this method derives native MSCs with high potency that can be directly transplanted into the patient right away - in the same manner as the HSCs from cord blood - without any significant manipulation. Although MSCs can be extracted from frozen minced cord tissue, in practice, the efficiency of MSC recovery post thaw is approximately 10% relative to native MSC extraction from fresh (not cryopreserved) umbilical cord tissue [3,4]. Another advantage of preparing therapy with "minimally manipulated" cells is that they are not subject to the more rigorous drug regulations that are imposed on cultured cell products.
MSCs are also being investigated for clinical applications in treating auto-immune diseases (diabetes, Crohn's disease, graft-vs-host-disease), neurodegenerative disorders (Parkinson's disease, Alzheimer's) and cardiovascular diseases (acute myocardial infractions, ischemia) .
In summary, the use of stem cells - namely HSCs and MSCs - for therapy of both blood and non-blood disorders in patients is an exciting development in medicine. Stem cells from umbilical cord blood and tissue should be saved at every opportunity - instead of thrown out - in order to give ailing patients the opportunity to reap the benefits of the curative power of stem cells in regenerative medicine.
- Friedman R, Betancur M, Boissel L, Tuncer H, Cetrulo C, Klingemann H. Umbilical cord mesenchymal stem cells: adjuvants for human cell transplantation. Biol Blood Marrow Transplant. 2007 Dec;13(12):1477-86. PMID:18022578. Full text
- Taghizadeh RR, Pollok KE, Betancur M, Boissel L, Cetrulo KJ, Marino T, Wolfberg A, Klingemann HG, Cetrulo CL. Wharton's Jelly derived mesenchymal stem cells: Regenerative medicine beyond umbilical cord blood. Placenta 2011, 32(Suppl 4):S339. Abstract
- Taghizadeh RR, Mrowiec ZR, Cetrulo KJ, Cetrulo CL. unpublished data, 2010.
- Briddell R, Litkenhaus F, Foertsch G, Fuhrmann A, Foster K, Girard KF, Fiscus B, Boehm A, Brown M, Pettit M, Bridges AR, Nichols K, Fodor W, Kraus M. Recovery of viable MSCs isolated from fresh umbilical cord tissue, measured after cryopreservation, is on average 8-fold higher when compared to recovery of viable MSCs isolated from previously cryopreserved umbilical cord tissue. Blood (ASH Annual Meeting Abstracts). 2011;118. Abstract 4398. Abstract
- Taghizadeh RR, Cetrulo KJ, Cetrulo CL. Wharton's Jelly stem cells: future clinical applications. Placenta. 2011 Oct;32 Suppl 4:S311-5. Epub 2011 Jul 6. Review. PubMed PMID:21733573. Abstract