STEM CELLS: FRAMING THE FUTURE OF HEALTHCARE
Stem cells are believed to have the ability to divide without limit and to give rise to specialized cells. Stem cell research is an exciting yet complex and controversial science. It holds the promise of helping us better understand the most fundamental p
Stem cells are believed to have the ability to divide without limit and to give rise to specialized cells. Stem cell research is an exciting yet complex and controversial science. It holds the promise of helping us better understand the most fundamental processes of cellular specialization and human development, and many nations have therefore invested heavily in stem cell research and its applications. Stem cell research is one of the most exciting areas of the 21st century science and has the potential to revolutionize the way we treat conditions, including regenerative diseases for which few effective treatments currently exist. There is a lot of hope invested in this field by researchers, governments and the general public.
Since the advent of induced pluripotent stem cells (iPSC) through the Nobel laureate winning revolutionary work of Shinya Yamanaka and colleagues, the field of pluripotent stem cell research and cell therapy development has seen an explosion in activity. Previously, this area had been limited to a few specialized centres that had access to and expertise in the culture of human pre-implantation blastocyst-derived embryonic stem cells.
“It spurred Japan, the country where iPSC technology emerged, into action with dedicated government support, to become a leader in cell therapy development, having the benefit of regenerative medicine for both the economy and their aging population in mind,” says Thorsten
Translating Center Director, IQVIA Stem Cell Center.
Scientists are engaged in discovering novel methods to create human stem cells. This is to address the increasing demand for stem cell production for potential investigation in disease management. This factor is certainly expected to accelerate the development of regenerative medicine, thus driving industrial growth. Moreover, cellular therapies are recognized as the next major advancements in transforming healthcare. Regenerative medicine is one of the fastest growing therapeutic applications of stem cells. It involves the usage of innovative medical therapies for the body to repair or replace the diseased or damaged cells.
Stem cell research is developing fast, with some experimental pluripotent stem cell treatments already in clinical trials. Commenting on the exciting advancements in the field of stem-cell research in recent times, Gorba says, “The new effective gene editing technologies will have a profound enabling and enhancing effect on stem cell and other cell therapies, including CAR-T (chimeric antigen receptor T-cell), immune-oncology (I-O) cancer treatments.”
Speaking on last year’s approvals of the Kymriah and Yescarta I-O autologous CAR-T therapies for leukemias he says “the approvals have provided a huge boost for the whole cell and stem cell therapy field, as evidenced by successful stock market IPO launches and availability of investor capital, despite, strictly speaking, autologous T-cell treatments not being stem cell therapies. However, next generation CAR-T and natural killer (NK) cell allogeneic, I-O therapies, derived from iPSC, are already in the late preclinical stage and will enter clinical trial soon. These new I-O products, aided by gene-editing modifications, have the potential to overcome limitations of the current autologous CAR-T products, e.g. lack of success in solid tumours, less side effects and the ability to effectively counter tumour evasion strategies. In addition, massproduced, “off-the-shelf” I-O cell products will have significantly reduced manufacturing costs per patient dose, will make wide-spread use and reimbursement in common cancers possible.”
Challenges and remedies
Active debates are underway to adapt regulatory frameworks to address the specific challenges of developing, standardizing, and distributing cell-based therapies, while advances in basic research continue to provide a fuller understanding of how stem cells can be safely and effectively used. Cell replacement or transplantation therapies are not the only application of stem cell research: already the first steps are being taken towards use of cells derived from pluripotent stem cells, in drug discovery and testing.
The field holds the potential to revolutionize the way human diseases are treated, and many nations have therefore invested heavily in stem cell research and its applications. However, human stem cell research is also controversial with many ethical and regulatory questions that impact a nation’s policies. Technical
Controlling stem cells isn’t easy. Both adult and embryonic stem cells present challenges. Though stem cells exist in adult tissue, they’re not present in great numbers, so they can be hard to find and to extract for growth.
Working with embryonic stem cells has its own challenges, too. Though they’re easier to grow into batches of unspecialized cells, researchers need to better understand how these cells reproduce in
“The approvals have provided a huge boost for the whole cell and stem cell therapy field, as evidenced by successful stock market IPO launches and availability of investor capital, despite, strictly speaking, autologous T-cell treatments not being stem cell therapies. However, next generation CAR-T and natural killer (NK) cell allogeneic, I-O therapies, derived from iPSC, are already in the late preclinical stage and will enter clinical trial soon. These new I-O products, aided by geneediting modifications, have the potential to overcome limitations of the current autologous CAR-T products, e.g. lack of success in solid tumours, less side effects and the ability to effectively counter tumour evasion strategies.” - Thorsten Gorba, Translating Center Director, IQVIA Stem Cell
the laboratory, and how to reliably trigger them to differentiate into the specific types of cells needed. There are also concerns that transplanted stem cells may not work in conjunction with the tissue of the person receiving them.
Because of the technical limitations involved in using adult stem cells, embryonic stem cells are generally preferred by stem cell researchers. However, we find ethical questions pertain to the use of embryonic stem cells.
The field of stem cell and generally cell therapies is still young. Consequently, most of the companies in it are young and small emerging biopharma, too. Gorba believes that there are some serious efforts needed to create, study, and ultimately use stem cells and their offspring in early-phase experimental human therapies and bring the most promising therapies from the lab into clinical trials in people.
“Often these are recent university spin-outs with few employees that know their science well, but lack the expertise and experience in formal drug development. When seeking help from independent consultants, emerging cell therapy companies will often have to grapple with confusing, or even contradictory and non-compatible pieces of advice. To make their research activities run smoothly, IQVIA has come up with an integrated asset development service, in which a cross-functional team of drug development and cell therapy experienced experts work together with the client to develop, a risk-balanced approach for the greatest likelihood of product success, in the fastest and most cost-efficient way. This integrated approach plans and considers preclinical and clinical development, as well as manufacturing and regulatory strategy together. An important tool for this plan is the generation of a target product profile (TPP), which tries to define the eventual label of the approved product, and specifies indication and patient population selection. A health economic outcome research (HEOR), will predict the market size for the product and its likelihood to be obtain commercially viable reimbursement. Hence, such an assessment will be of great value for devising a manufacturing strategy that will be able to meet demand sustainably, at a reasonable cost of goods. Once a therapy candidate reaches clinical trials, enrolment projection and site selection optimization, will avoid costly delays in enrolment and timely trial completion for companies with a limited financial runway.”
Gorba, who is optimistic of the future of stem cell research in the coming years, concludes, “During the coming 10 years, the first wave of stem cell therapies that we will see progression from clinical trials to the market and general patient populations, are tissue-derived stem cells, with the majority of near future approved products expected to fall into the two dominant cell type categories mesenchymal stem cells (MSC) and gene-modified hematopoietic stem cells (GM-HSC). Next, the iPSC revolution will then manifest itself with a second wave of pluripotent stem cell-derived regenerative medicine product clinical trials, and perhaps the first couple of approvals.
These cell therapy products will provide functional replacement of lost and impaired cell types with the aim of true regeneration and restoration; setting back the clock on diseases, rather than just halting their progression. In addition to pure cell therapies, tissue engineering 2.0, based on stem and progenitor cell technologies, will make a revival”.
Much remains to be learned about stem cells, including potential hazards. Real applications, for the most part, are still years away. But if progress with blood and bone marrow transplants is any indication, stem cell research may someday help many people. These cells may significantly advance disease treatment and expand human knowledge of the body’s basic processes.