Clearly, stem cells are not a cure-all: but what can science do to bring them closer to this ideal?
By RUSTAM GILFANOV
Exactly 40 years ago, the future Nobel Prize winner Martin Evans published his study on mouse embryos stem cells and their medical potential . His research revolutionized biomedicine, as it envisioned the future, in which any damaged tissue could be replaced by a new one, grown in vitro from the patients cells.
What has changed since 1981? Are we approaching the times when regeneration and artificial organs become a reality? Or did the research tendencies change, with regeneration going out of style? Here, I will try to outline several major trends.
There are two types of stem cells: embryonic and tissue cells.
The embryonic ones can transform into any other cell type. A fetus consists of these very cells during days 3-5 of gestation. And if kept in a special environment, they can divide almost infinitely, while remaining unchanged.
A small number of tissue stem cells can be found in the organs of adult people. They help to restore damaged tissues and can transform into one particular cell type only. Eventually, scientists have learned to make embryonic cells analogs out of them that can be used for growing various tissue types. Since the days of Martin Evans, they have been called pluripotent stem cells.
The discovery of these two cell types led to the rapid development of regenerative medicine. The pathologies it could potentially cope with include strokes, cardiovascular diseases, diabetes, Parkinsons and Alzheimers, ALS, osteoarthritis, severe burns, and even various oncological diseases. However, we must admit that as of 2021, regenerative medicine has been unable to achieve such outstanding results.
In 1998, the technology was discovered that allowed to separate embryonic stem cells from the organism and grow them in vitro, i.e., literally transform them into tissues of any type . Thus, regenerative medicine moved from theory to practice, as it became possible to work with stem cells in laboratory conditions.
Stem cells are already contributing to science not directly as a therapy method, but implicitly as a way to study various important aspects. For instance, by watching them develop into bone, nerve, or some other cells, medics and scientists get a better understanding of how hereditary diseases are progressing.
Besides, pharmacologists apply stem cells for testing new medications. For human trials to start, a drug must be proven to be safe. To do this, tissues originated from stem cells are used: e.g., it is possible now to grow nerve cells for testing a new medication against neurological diseases. Such tests can reveal positive or adverse effects in advance and, in theory, accelerate randomized controlled trials by helping to avoid lengthy and burdensome legal procedures. However, this method remains more expensive than traditional, albeit slow, enrollment of candidates.
Despite outstanding research results, medics actively apply only one method of stem cell therapy bone marrow transplants for blood cancer treatment.
Many constraints hinder regenerative medicine breakthroughs. One of them is unpredictability: the researchers must be sure that stem cells will transform into the tissue they are planning to get. Also, medics need to learn to regulate the development and multiplication of stem cells to prevent an uncontrolled division of cells that causes malignant tumors.
Besides, the immune system may attack embryonic stem cells mistaking them for invaders, while modern medicine is lacking tools for adjusting this immune response. We can see the consequences of this in real time during the COVID-19 pandemic, with thousands of people dying because of the aggressive and unbridled immune response, not because of the direct impact of SARS-CoV-2.
It must also be taken into consideration that current technologies are demonstrating a lot of side effects. Patients with multiple sclerosis, who received stem cell treatment, suffered from low platelet and white blood cell counts, infections, and toxic liver damage .
Another problem is the expensiveness of this method. One session of the MS treatment listed above cost 40, 000 pounds.
Finally, there is another constraint that still cannot be overcome and is related to technological and ethical issues. The revolutionary 1998 report that I mentioned earlier stated the embryo that lent stem cells to the researchers was destroyed. From the humanistic perspective, we are walking the thin line between killing a potential living being for an already existing one and simply manipulating with cells.
In 2006, Japanese researcher Shinya Yamanaka offered a solution to this dilemma: he developed the so-called induced Pluripotent Stem Cells (iPSC), de facto providing an analog to embryonic cells that is based on somatic cells of adult persons. In this case, there is no need to destroy an embryo; for this achievement, professor Yamanaka has been rightfully awarded the Nobel Prize in Physiology or Medicine. Nevertheless, while solving one problem, this method actually caused a new one.
Scientists have found that iPSCs have a high potential for causing tumors and the risk of malignancy is too serious to start using these cells for therapeutic purposes.
Thus, the only morally acceptable method of using embryonic stem cells available to us at the moment is using mouse embryos cells this technology has been tested and is relatively well-developed, even though it remains quite expensive .
We have to admit that now, 40 years since Martin Evans discovery and 23 years since the first successful in vitro stem cell manipulations, reproductive medicine is still taking its baby steps. There are many research programs but only a few technologies made it to mass production. Yet even these intermediate results seem astonishing.
For example, in 2016 a team of scientists from Greece and the UK attempted to regenerate muscle tissue of infarction patients by transplanting myocardium cells that had been grown in the lab . As a result, cardiac callosity was reduced by 40%. Before that, such damages had been considered untreatable. However, only 11 people took part in the research and this number is too small to draw any firm conclusions.
Scientists are gradually improving the technologies they implement. Here is an example. The immune system may attack the stem cell transplant, mistaking it for a foreign object. This is why medics are working on culturing cells that do not provoke an immune response. In 2020, researchers from Karolinska Institutet and St. Eric Eye Hospital (Sweden) found a way to improve the production of retina cells from embryonic stem cells for treating blindness among aged patients . They managed to alter the cells so that they can hide from the immune system instead of being destroyed by it.
Another promising technology involves stem cells already existing in the body. During an experiment conducted by the University of Illinois researchers, nanoparticles with molecules stimulating stem cell activity were introduced to damaged muscles of rats . As a result, muscles were recovering faster and the animals were able to walk longer distances, compared to traditional treatment.
Standalone cases have also been a huge success. In 2019, Japanese medics, for the first time in history, transplanted hepatocytes grown from human embryonic stem cells to a six-day-old baby: the childs liver did not have the enzyme that transforms nitrogen-containing breakdown products into urea. Thus, a rare congenital disease was blocked . Scientists think that stem-cell hepatocyte transplantation, with its effectiveness and safety tested by this case, can be applied in the future not only for treating congenital urea cycle disorders but also for helping patients who need to wait for a liver donor.
One year prior, in 2018, the scientists de facto grew a human heart from iPSCs. They cultured a contracting myocardial tissue, with its characteristics (gene expression, structure, etc.) identical to the functioning cardiac tissue of an adult person . Although it is impossible to transplant this artificial heart to a patient, the experiment turned out to be useful for testing new drugs.
In 2020, 13 patients with spinal cord injuries received an experimental therapy that involved stem cells. Because of the injuries, they suffered from such neurological symptoms as loss of motor function and body sensitivity, bowel and bladder dysfunction, etc. All patients were given intravenously several dosages of mesenchymal stem cells (multipotent cells capable of transforming into various cell types including neurons) cultured from their own marrow. 12 out of 13 participants showed significant improvement in the following six months and these results are extremely encouraging .
Experiments on rats conducted by Swedish researchers led to an even more impressive outcome: the scientists achieved the post-stroke recovery of animals neurons by using iPSCs. To do this, they reprogrammed human skin cells and the synthesized neurons quickly adapted to the neural system. Six months after the transplantation, all signs of brain damage caused by the stroke have disappeared and the rats regained their motor functions and sensitivity to the touch . However, the impact on test subjects personality cannot be estimated this can become a major constraint for performing such potential transplantations on humans.
Summing up, almost every week a new article boasting successful stem cell research can be found in scientific journals. Yet all these experiments do not bring us closer to a victory over any severe disease or at least prove that regenerative medicine is reaching a new level. What is the matter, then?
1. The stem cell market reached 14.7 billion dollars in 2020 and is estimated to grow up to 26.4 billion by 2026. In other words, it is expected to double in the next five years. This is a very favorable forecast and investors are stocking up shares of stem cell research companies, boosting their value and expanding the market.
Do you get what I mean? The belief in stem cells and their ability to solve almost any medical problem has turned this market into a bubble that can burst any moment, putting these exorbitant investments to waste. What is worse, this crisis will suspend ongoing medical research, possibly stymieing The One that could give us a really effective and scalable technology for treating cancer or cardiovascular diseases.
Market players, investors, and stem cell researchers themselves should lower their expectations so that the bubble stops growing on high hopes alone. The value of shares and investments must grow according to actual discoveries and successes this will be more beneficial to science than any boom caused by ungrounded attention. This is what happened to the revolutionary CRISPR-Cas technology: from the big business perspective, it came out of nowhere; yet now it is really changing the world.
2. The stem cell industry (both investors and researchers) need to focus on the COVID-19 pandemic. Some studies are already attempting to fight COVID-19 with iPSC technologies; yet even if they fail (we do not have effective medications against various viruses and it is unlikely we get the ones treating SARS-CoV-2), it is necessary to seize the moment.
This may sound too calculated or cynical, but the attention of governments, businesses, and the public to the healthcare industry will not always be as high as it has been during the pandemic. Now it is the right moment to attract money, technologies, and human resources by the mid-2020s, if COVID-19 is taken under control, they can be successfully transferred to other areas of medicine.
3. It is essential to take advantage of information technologies. Experiments on mice are unable to quickly assess various mechanisms of stem cell functioning, especially given the rigid ethical restrictions on human testing. The successes and achievements that I mentioned in this article, as well as thousands of others, are just a drop in the ocean compared to what is required to help regenerative medicine evolve into a fully functioning discipline.
Present-day computer models offer unique opportunities for in silico research technically, we already have reliable virtual patients for testing even such complex methods as cell reprogramming. Virtual clinical trials remove ethical constraints and enable the quick collection of data available to scientists from all over the world, who are conducting similar studies. There is no need to get rid of classical research methods, yet widespread in silico technologies can accelerate stem cell research multiple times.
4. Even before Dolly the sheep was born, people had been debating on the moral aspects of cloning living creatures, especially humans. Nowadays, legal restrictions on such procedures are imposed in many countries, while regulation of stem cells is still in its embryonic stage with no reprogramming in sight.
Specialists from various industries healthcare, law, IT, pharmaceutics, and fundamental science including humanities (e.g., researchers on morality, ethics, and philosophical notions of the digital age) need to join their efforts and set the adequate rules of this game. What stem cells can be used and in what situations? Which reprogramming types are acceptable and which are not? What are the moral limits of clinical trials and therapy involving stem cells? Lots of questions still need answering and provisioning these answers in codes and guidelines.
To truly make stem cells and regenerative medicine the next big thing, instead of becoming just another fashionable trend or a market bubble, we need to work this out. And we need to do it together.
Rustam Gilfanov is an IT entrepreneur and a venture partner of the LongeVC fund
- University of Michigan Stem Cell Research | Frequently ... - November 30th, 2021
- Postdoctoral Research Associate in Centre for Stem Cells and Regenerative Medicine job with KINGS COLLEGE LONDON | 273388 - Times Higher Education... - November 30th, 2021
- Stem cell therapy potentially could treat Type 1 diabetes by helping patients produce insulin - USA TODAY - November 30th, 2021
- UCLA Broad Stem Cell Research Center receives $5 million ... - November 30th, 2021
- ReproCELL Incorporated : Everything you need to know about the REPROCELL iPSC Biobank - marketscreener.com - November 30th, 2021
- Cell therapy biotech Quell adds $156M for alternative to organ transplant meds - MedCity News - November 30th, 2021
- New nanochip reprograms cells in the body to perform different functions - New Atlas - November 30th, 2021
- Inside the Innovative Lab Growing Mammal Tissue Using Plants as Scaffolds - Smithsonian - November 30th, 2021
- BrainStorm Cell Therapeutics Announces the Presentation of New Analyses from the Phase 3 Trial of NurOwn in ALS at the 4th Annual ALS ONE Research... - November 30th, 2021
- 'Sleeping' cancer cells explain why childhood leukaemia returns after years of treatment - The Institute of Cancer Research, London - The Institute of... - November 30th, 2021
- 10 rare cancers: Symptoms, treatment, and more - Medical News Today - November 30th, 2021
- Heart repair and regeneration after a heart attack a review - The Mix - November 30th, 2021
- InGeneron Publishes Significant Support for the Existence of Naturally Pluripotent Stem Cells in All Organs in the Adult Body - StreetInsider.com - November 27th, 2021
- How the CGT Catapult plans to bridge the gap between scientific research and commercialisation - The Scotsman - November 27th, 2021
- Global $512M+ Exosome Diagnostics & Therapeutics Market, 2026 | Featuring Profiles of Codiak Biosciences, Evox Therapeutics, Exosome Diagnostics,... - November 27th, 2021
- Discovering a new gene in monkeys that could help to develop new antivirals - News-Medical.net - November 27th, 2021
- 2nd Person May Be Naturally 'Cured' of HIV: What Science Is Learning - Healthline - November 27th, 2021
- Research Roundup: Masking Cuts COVID-19 Risk in Half and More Research News - BioSpace - November 27th, 2021
- Stem Cell Research Facts - November 24th, 2021
- InGeneron Publishes Significant Support for the Existence of Naturally Pluripotent Stem Cells in All Organs in the Adult Body - marketscreener.com - November 24th, 2021
- Research Developments in the Treatment of Advanced Kidney Cancer - Warwick Beacon - November 24th, 2021
- Covid vaccine: Stem cell transplant patients who must be completely re-vaccinated struggling to book jabs - iNews - November 24th, 2021
- Amity University partners with top US varsities for academics and research - Telegraph India - November 24th, 2021
- AML relapse: Definition, statistics, and treatment options - Medical News Today - November 24th, 2021
- Its too late for me but please help others with cancer - Melton Times - November 22nd, 2021
- Research Developments in the Treatment of Advanced Kidney Cancer - The Apopka Voice - November 22nd, 2021
- How The Overlap Between Artificial Intelligence And Stem Cell Research Is Producing Exciting Results - Forbes - November 22nd, 2021
- California Proposition 14, Stem Cell Research Institute ... - November 22nd, 2021
- Theres Something Neurological Going On, COVID Could Cause Depression And Anxiety, Researchers Say - CBS Baltimore - November 22nd, 2021
- Exosome Diagnostics and Therapeutics: Global Markets - Yahoo Finance - November 22nd, 2021
- Flying cars and floating cities these 8 radical designs predict our imminent future - Boston News, Weather, Sports | WHDH 7News - November 22nd, 2021
- Researchers discover new type of cell that may help regulate heart rate - News-Medical.net - November 22nd, 2021
- The Promise of Stem Cells to Help Children with Autism - Entrepreneur - November 21st, 2021
- Stem cell transplants without chemo and radiation first? - Futurity: Research News - November 16th, 2021
- Unregulated Stem Cell Clinics Endanger Patients And Limit Research - Forbes - November 16th, 2021
- Regenerative Medicine Market Size Worth $ ~41.45 billion by 2031 - Market Size, Share, Forecasts and Trends Analysis Report with COVID-19 Impact by... - November 16th, 2021
- Stem Cell Therapy Reduces Need for Nearly 10% of Hip Replacements - Yale School of Medicine - November 16th, 2021
- Overlooked DNA may be what separates humans from other primates study - The Jerusalem Post - November 16th, 2021
- In-depth Research on Cancer Stem Cell Market Forecast Estimation & Approach 2021-2026 | Thermo Fisher Scientific, AbbVie, Merck KGaA, Bionomics,... - November 16th, 2021
- NK Cell Therapy and Stem Cell Therapy Market Cumulative Impact for COVID-19 Recovery Research Report 2021 | Takeda Pharmaceutical, JCR Pharmaceutical,... - November 16th, 2021
- Stem Cell Therapy Market Analysis By Trends, Size, Share, Company Overview, Growth And Forecast By 2027|Osiris Therapeutics, NuVasive, Chiesi... - November 16th, 2021
- Hoth Therapeutics Announces a Sponsored Research Agreement to Further Develop Novel mRNA Cancer Therapeutic HT-KIT - Yahoo Finance - November 16th, 2021
- Research Antibodies Market Size Is Projected to Reach $6.35 Billion by 2028 | CAGR: 6.5% : Polaris Market Research - PRNewswire - November 16th, 2021
- Jasper Therapeutics Announces Third Quarter 2021 Financial Results and Provides Business Update - Tyler Morning Telegraph - November 16th, 2021
- $2.26 million in grants will support biomedic - EurekAlert - November 16th, 2021
- Jasper Therapeutics Announces Research Collaboration with AVROBIO to Evaluate JSP191 as Conditioning Agent in Clinical Studies of Ex Vivo Lentiviral... - November 11th, 2021
- Stem Cell Characterization and Analysis Tool Market 2021 Detailed Analysis of top Ventures with Regional Outlook | Key Companies: Osiris Therapeutics,... - November 11th, 2021
- Global Stem Cell Umbilical Cord Blood (UCB) Market Insightful Research Report: Business Growth, Development Factors, Current and Future Trends and... - November 11th, 2021
- Century Therapeutics Reports Third Quarter 2021 Financial Results and Provides Business Updates - The Bakersfield Californian - November 11th, 2021
- 2021 Boston Investment Conference Marks Decade of Helping Fund Critical Research at Boston Childrens Hospital - Yahoo Finance - November 11th, 2021
- Yale researchers develop RNA-based therapy that clears SARS-CoV-2 from mice - EurekAlert - November 11th, 2021
- Critical Link Discovered Between Dietary Fat and the Spread of Cancer - SciTechDaily - November 11th, 2021
- Opinion | How Covid Raised the Stakes of the War Between Faith and Science - The New York Times - November 11th, 2021
- EdiGene to Present Latest Research on A Novel Surface Marker and Migration of Hematopoietic Stem Cell (HSC) That Could Enhance HSC Gene Therapy and... - November 5th, 2021
- Century Therapeutics to Present at the 63rd American Society of Hematology Annual Meeting and Host Virtual Research & Development Update - Yahoo... - November 5th, 2021
- City of Hope Doctors Present New Research on Cancer Immunotherapies - Business Wire - November 5th, 2021
- Mini-brain model of frontotemporal dementia demonstrates the stages of dysfunction that lead to cell death - National Institute on Aging - November 5th, 2021
- Intestinal Organoids and Their Role in Tissue Engineering - Technology Networks - November 5th, 2021
- Magenta Therapeutics Reports Third Quarter Financial Results and Program Highlights - Business Wire - November 5th, 2021
- Researchers generate and characterize the hepatic organoid culture system - News-Medical.net - November 3rd, 2021
- A major research project to advance regenerative therapy for epidermolysis bullosa (EB) using transgenic stem cells - PR Web - November 3rd, 2021
- Canada Biobanks Markets, Analysis & Forecasts, 2016-2020 & 2021-2026 - Increased Research and Technological Advancement in Genomic Studies -... - November 3rd, 2021
- Study paves the way for a better understanding of muscle injury - News-Medical.Net - November 3rd, 2021
- Lab-Growing Everything Might Be The Only Way To Attain A Sustainable World - Intelligent Living - November 3rd, 2021
- What is Stem Cell Research? | The Benefits of Stem Cell ... - October 26th, 2021
- New Treatments and Tips for Dealing With Blood Cancer - Curetoday.com - October 26th, 2021
- NK Cell Therapy and Stem Cell Therapy Market Cumulative Impact for COVID-19 Recovery Research Report 2021 | Chiesi Pharmaceuticals, Takeda... - October 25th, 2021
- Skroot Laboratory, Inc. Joins Cell Manufacturing Research Initiative to Further Advance Cell Therapy Discovery - KOLO - October 23rd, 2021
- New GBM research pipeline and being glad - Brain Tumour Research - October 23rd, 2021
- Excellent Growth of Cell Separation Technology Market by Trends, Dynamic Innovation and Key Players GE, BD, Terumo, Merck, Thermo Fisher | Forecast... - October 23rd, 2021
- Misinformation on stem cell treatments for COVID-19 linked to overhyped science, researchers argue - UB Now: News and views for UB faculty and staff -... - October 21st, 2021
- What Makes Us Human? The Answer May Be Found in Overlooked Junk DNA - SciTechDaily - October 21st, 2021
- Stem Cell Therapy Market SWOT Analysis, Key Indicators, Forecast 2027 | Anterogen Co., Ltd. (South Korea), MEDIPOST Co., Ltd. (South Korea), Osiris... - October 21st, 2021
- Stem Cell Therapy Market: Shaping Tomorrow with Anterogen Co., Ltd. (South Korea), MEDIPOST Co., Ltd. (South Korea), Osiris Therapeutics Puck77 -... - October 21st, 2021
- Liu receives Catalyst Award from the National Institutes of Health agency - Harvard School of Engineering and Applied Sciences - October 21st, 2021
- Stem Cell Therapy Market 2021 Financial Highlights Analysis with Top Key Players: Anterogen Co., Ltd. (South Korea), MEDIPOST Co., Ltd. (South Korea),... - October 21st, 2021
- Stem Cell Therapy Market 2025 Size, Key Companies, Trends, Growth And Regional Forecasts Research | Anterogen Co., Ltd. (South Korea), MEDIPOST Co.,... - October 21st, 2021
- Scientists use human-derived brain cells to develop more realistic 'disease-in-a-dish' models of Alzheimer's - National Institute on Aging - October 21st, 2021
- Harvard's R&D alliance with Resilience to advance manufacture of complex medicines - Harvard Gazette - October 17th, 2021
- Research Roundup: T-Cell Immune Response to COVID-19 Vaccines and More - BioSpace - October 17th, 2021