Asymmetrex’s 3-month campaign to increase awareness of the adult tissue stem cell counting problem has focused on how its AlphaSTEM technology solution could impact research and clinical practice. Now, the final post in the series discloses the greater human impact of tissue stem cell counting.
The final installment of Asymmetrex’s adult tissue stem cell counting awareness campaign, hosted by RegMedNet from January through March, considers the envisioned greater human impact of the company’s AlphaSTEM technology for counting tissue stem cells. The previous five RegMedNet blog posts and the culminating March 22 webinar emphasized the application of AlphaSTEM technology to address several unmet counting needs in stem cell research, regenerative medicine, and drug development. Each of the applications considered ultimately impacts the lives of patients seeking better treatments for debilitating illnesses for which cures are hard to come by. As described in detail below, the implementation of tissue stem cell counting can impact patients and their families in many significant ways, including accelerating progress in basic and clinical research for new therapies, lowering costs for new medicines, and directly increasing the efficacy of approved regenerative medicine treatments and the effectiveness of experimental ones.
Human impact of counting for umbilical cord blood hematopoietic stem cell transplantation
The longest available approved stem cell therapy is transplantation of hematopoietic stem cells (HSCs) to reconstitute blood cell production. The primary indication for such treatments is for rescue of cancer patients after their own hematopoietic system has been ablated in the course of intensive chemotherapy and radiation therapy to eradicate cancer cells. Donors of normal, matched bone marrow — a major source of HSCs — are sometimes scarce, especially for ethnic minorities for whom there are fewer prospective donors.
Umbilical cord blood serves as another source of donor HSCs. However, because cord blood collections have fewer HSCs, their reliability is much less than bone marrow collections. Whereas the rate of transplantation graft failure due to insufficient HSCs can approach 1% for bone marrow treatments, it ranges from 10-25% for cord blood, being higher for older children and adults, who require larger amounts of HSCs for successful transplant engraftment.
In the U.S. alone, the failure rate of 10-25% means the death of about 200 patients each year who might have lived if the number of HSCs in the treating cord blood had been determined before it was used. Many of these deaths are of children suffering from acute myelogenous leukemia (AML). They wait with their families for nearly 2 months in dread to see if their cord blood has enough HSCs to rescue them from their leukemia treatment. Yet, the anguish of their wait is only a part of the larger desperate human experience with cord blood transplantation. The many hundreds more patients, young and older, who have successful transplants must also endure the anxious wait to learn if their transplant had enough HSCs.
The most immediate human impact of the AlphaSTEM counting technology would come from its rapid deployment for determining the number of HSCs in cord blood transplantation preparations before their use for treatment. Establishing the HSC count as a standard cord blood bank procedure would also address the long-standing need for a cord blood potency measure.
Going forward, HSC counting could certainly be performed before the storage of future cord blood samples. However, if existing stored samples were confirmed to retain effectiveness after thawing and re-freezing, the human impact could be profound. There are estimated to be nearly 700,000 stored cord blood samples worldwide. Some estimates indicate that maybe only 10% of these samples are feasible for treatment based on having higher total cell counts. Whereas the extremes of total cell counts are qualitatively related to transplant success, no quantitative relationship between HSC number and total cord blood cell count has been determined. Defining the terms of such a relationship could identify many more existing cord blood samples effective for transplant treatment.
Human impact of counting for hematopoietic stem cell transplantation
The most mature and effective stem cell medicine is HSC transplantation using either bone marrow or mobilized peripheral blood stem cells. The yearly number of transplants in the U.S. is about 19,000; and worldwide about 68,000 are performed each year. As noted earlier, because typically a large number of HSCs are present in these collections, the failure rate attributable to too few stem cells approaches 1%. However, because of the large number of HSC transplants performed, this small percentage still means that hundreds of additional lives could be saved each year if the number of HSCs were determined in all transplant preparations to insure sufficient numbers.
The increase in treatment cost with stem cell counting would be incremental compared to current costs for HSC transplant. The average cost of transplants with bone marrow or mobilized blood stem cells is about $40,000 USD. This number increases to an average of $200K USD for cord blood transplantation.
Another important human impact consideration for HSC transplantation is that, with such a low failure rate, many current patients are receiving an excess of HSCs needed for survival. Masked by the great number of transplants performed each year, there is still a significant shortage of transplant donors for ethnic minorities. In these cases, counting the number of HSCs may reveal the possibility of multiple transplants by dividing existing samples. General application of HSC counting to all incoming donor samples might also reduce the size of the ongoing effort required each year by government agencies to secure sufficient transplant units to meet the general need.
Human impact of counting for early detection of organ failure during drug development
Current estimates of the cost of successfully achieving the advance of a single drug candidate from pre-clinical testing to the marketplace is >$2 billion USD and increasing yearly. For the U.S. pharmaceutical industry this number translates into around $50 billion USD in expenditures each year to bring 20 to 30 new drugs to the marketplace. A great deal of this cost is passed on to patients and their insurers in the form of higher medication prices. Currently these economics are a hotly contested issue. Several drug companies have sought significantly elevated drug prices only to be rebuked by government regulators, patient advocacy groups, and politicians.
Much of the drug development costs are spent on a small number of lead candidates that advance to pre-clinical animal testing and clinical trials where they fail. One of the major causes of failure, accounting for 20-30%, is safety. Drugs can be too toxic acutely or chronically. Chronic toxicity resulting in organ and tissue failure accounts for about half of the failures for safety. This form of organ and tissue failure is the signature of tissue stem cell toxicity.
A means of predicting earlier which drug candidates will fail later in more costly pre-clinical animal studies and clinical trials, due to tissue stem cell toxicity, could save the U.S. pharmaceutical industry as much as $5 billion USD each year. These savings could equate to hundreds of millions of dollars for large pharmaceutical companies, as well as proportional rebates of the current drug development costs of smaller companies. Asymmetrex’s AlphaSTEM technology offers this capability by being able to score effects of drug candidates on stem cell number, viability, and tissue renewal function with an inexpensive cell culture assay. So far, AlphaSTEM detection of tissue stem cell toxicity has been validated as an indicator of hematopoietic tissue and liver organ failure.
The human impact of adoption of AlphaSTEM technology for evaluating drug candidate stem cell toxicity is both local and distant. Closer to its application, it will increase safety for the thousands of research subjects and patients participating in drug development clinical trials each year. More far-reaching, its implementation can drive down the cost of developing new, needed drugs by procuring significant direct savings for pharmaceutical companies and by accelerating drug development. Every candidate confidently removed from the drug development process because of stem cell toxicity reduces the cost and time needed to identify the candidates that will succeed.
Human impact of counting for regenerative medicine clinical trials
The number of stem cell therapy clinical trials worldwide is approaching 500. Currently, none of these trials has a means to determine the doses of the tissue stem cells under investigation. In the case of trials based on autologous transplants, this situation renders their results largely non-interpretable, because the crucial basis of comparison from one patient to another, stem cell dose, is unknown. The same will be true of allogeneic treatments, in which individual transplants are used because the recipients differ from each other in haplotype. This situation is a great loss to both the study participants and the many patients hoping that these trials will yield better treatments for many presently refractory disorders and injuries.
Human impact of counting for tissue stem cell research
Despite the greater attention on clinical investigations in regenerative medicine, basic stem cell biology research is still indispensable for ideal progress in stem cell medicine. The basic challenges of identifying, quantifying, and producing adult tissue stem cells for applications in clinical medicine still require significant increases in knowledge of the basic biology of the cells. Moving any field of science from qualitative estimation to quantitative measurement is a significant moment that is followed by acceleration in knowledge and technological development. To the degree that adoption of AlphaSTEM technology is such a moment in the history and science of cell biology, its impact is expected to be far-reaching for increasing the quality of human life by improving existing medicines and reducing the barriers to discovery of new, more powerful ones.
If you are interested in reading more about counting adult tissue stem cells, our previous posts can still be found online and furthermore the webinar ‘A first technology for counting adult tissue stem cells for applications in regenerative medicine and drug development’ is now available to view at any time!