Back in 2006, a statement a few months after the birth of Leonor de Borbón, the first-born daughter of King Felipe and Queen Letizia of Spain, caused a stir that rippled beyond the Spanish border. The royal household had decided to store the newborn’s umbilical cord at a blood bank in the US, arguing that should Leonor someday fall ill, the stem cells harvested from it could be used to treat her – or even cure her parents’ ailments. Observers in Spain and beyond began to wonder whether they ought to follow the royal example and freeze their own infants’ umbilical cords, too. In the following years, the practice in Spain rose dramatically, as did the number of stem-cell banks. Even if they didn’t yet know exactly how this genetic material could be used, many people were keen to invest in what they hoped would be a “cellular insurance” for the future.

The story of stem-cell research can be mapped through a series of milestones, the first of which came in 1981 when Martin Evans, then of the University of Cardiff, first identified embryonic stem cells in mice. Then, in 1997, the world met Dolly the sheep, the first cloned mammal to be created from an adult cell, created by Ian Wilmut and his team at Edinburgh’s Roslin Institute. Finally, in 1998, the prospect of stem-cell treatment became tantalisingly real when James Thomson and John Gearhart, researchers at the University of Wisconsin and Johns Hopkins University respectively, successfully isolated human stem cells and grew them in a laboratory. In 2006, Shinya Yamanaka, a scientist at Kyoto University, identified a method for creating pluripotent cells from mature cells, allowing his team to convert ordinary mature cells into induced pluripotent stem cells through reprogramming – thus avoiding the need to destroy the embryos themselves. In 2007, Martin Evans, Mario Capecchi and Oliver Smithies received the Nobel Prize for Medicine for their work on genetics and embryonic stem cells, firing the starting pistol once and for all.

Dr William Hogan, a haematologist at Mayo Clinic and current head of its Bone Marrow Transplant Program, remembers those first experiments well. “At the beginning of my career at the Fred Hutchinson Cancer Center, I had the privilege of working with E Donnall Thomas and his team, of which Dr Rainer Storb was a member.” Dr Thomas won the Nobel Prize in Physiology or Medicine in 1990 for his work on bone marrow transplants. “For me, it all comes down to personal stories where the life of a person and their family is turned around by a treatment that works. Every day we face challenges and enjoy huge successes, but meeting a transplant survivor over 60 years old was the most inspiring moment of my career,” says Hogan. The doctor is referring to the first stem-cell transplant performed at Mayo Clinic in 1963 on a seven-year-old girl with aplastic anaemia. In 2023, he had the opportunity to meet with both the donor and the recipient to celebrate her 60th birthday. “It was a great experience to see how that child with a fatal illness could be celebrating her life six decades later,” he recounts.

© iStock

Stem cells derived from umbilical cords, like those from the Spanish princess, are the most plastic and versatile. They can renew themselves and differentiate into other types of highly specialised cells. “Stem cells have the unique ability to transform themselves into the kind of cells that the organism needs, where and when required. That’s why they are crucial in repair and regeneration processes,” notes Robin Mesnage, a researcher at the Clinic Buchinger Wilhelmi. They are considered pluripotent stem cells because of their ability to divide into other stem cells or turn into any other type of cell. On the other hand, so-called mature stem cells, found in small quantities in adult tissues such as bone marrow and fat, have a limited capacity for regeneration. Kyoto University’s 2006 breakthrough substantially reduces the risk of immune-system rejection and greatly increases the success of transplants.

Stem cells are one of the pillars of regenerative medicine, a discipline that, according to Dr Hogan of Mayo Clinic, “spans a wide range of interconnected concepts. The use of stem cells constitutes one of the most successful strategies for harnessing the full potential of regenerative medicine to treat blood-related diseases such as leukaemia and bone marrow failure disorders,” he explains. “These early successes led to other innovations, such as generating personalised immune cells like CAR-T cells or developing specific antibodies to improve the function of immune cells.”

Those suffering from leukaemia, Hodgkin’s lymphoma and some solid tumours may benefit from stem-cell therapies, as may those suffering from immunodeficiency and hereditary metabolic diseases. The regenerative potential of these cells for the treatment of type 1 diabetes, Parkinson’s disease, amyotrophic lateral sclerosis, congestive heart failure and osteoarthritis has been widely studied. “We’re living in a wonderful time in which lots of therapies under development are becoming real treatment options for many diseases. Never before has progress been so fast. The latest innovations have completely changed the prognosis for patients suffering from various kinds of cancer, or inherited disorders like thalassemia, haemophilia and sickle cell anaemia. They’ve also improved the treatment of autoimmune diseases like scleroderma, or neurological ones like multiple sclerosis. Their applications are very wide and new treatments are being approved almost daily,” enthuses Dr Hogan.

One thing is certain: the application for stem cells seems endless – at least in theory. There are even hair-loss treatments that purport to regenerate hair and stimulate regrowth. Although it is a challenge to manipulate these cells outside a clinical setting – and the task itself is rather complex to explain or even understand – cell therapies are the words on everyone’s lips worldwide.

 © SHA Wellness Clinic Mexico

“The safest, most effective and most established use of stem cells is bone marrow transplants to treat certain kinds of cancer, like leukaemias and lymphomas, especially to repair the damage wrought by chemotherapy on blood cells,” maintains Mesnage, adding that there is not currently sufficient proof for stem cell’s efficiency for enhancing longevity – or for aesthetic purposes. “There’s a lack of standardisation, and the trial results still depend greatly on clinical variables,” he adds.

According to Dr Hogan, complex treatments, such as transplants, may lead to severe toxicities, so it’s important to choose both your clinic and doctor carefully. “The clinic must have an excellent reputation, an approach that centres [on] the patient, and access to a wide variety of resources and subspecialists to collaborate with if complications arise.”

The safety and effectiveness of these therapies and, above all, the balance between risks and benefits have kept the scientific community on tenterhooks. Before administering a drug containing stem cells to human beings, the possibility of severe side effects must be ruled out. “Every treatment involves some risk, so an individual evaluation of the risk-benefit balance must be performed,” says Hogan. “Of course, in light of these thrilling advances, experience and judgment are often underestimated when deciding which treatment is the most appropriate for each patient. At Mayo Clinic, we believe that technological advances are another tool to provide excellent results centred on the patient, but choosing the strategy most suitable for each patient remains one of the most critical tasks in medical care,” he warns.

At the turn of the millennium, the use of stem cells unleashed an ethical controversy that remains unresolved. Every nation has its own legislation regulating both research and its application in treatments on real patients. In Spain, for example, the Biomedical Research Law, which came into effect in 2007, allows for the use of embryos for therapeutic or research purposes, meaning that any therapy involving stem stells must be conducted within the framework of a clinical trial or investigative process. In France, research involving this type of cell is permitted as part of research projects involving human beings, and on the condition that the cells are used by a scientific institute. In Germany, by contrast, the use of embryonic cells is heavily restricted by a 1991 law that considers the manipulation of embryos “a criminal offence”. The German constitution protects embryos with the argument that “human dignity must not be violated”. Since 2002, the law has favoured research utilising mature stem cells. Another law, which came into effect in 2008 following pressure from the scientific community, allowed the use of embryonic stem stells in research provided that their use is vital to the development of new drugs or for scientific progress. In 2009, Barack Obama removed some restrictions on using federal funding for research using human embryonic stem cells in the United States: before this order, only research with non-embryonic stem cells existing before 2001 could be federally funded.

© Institute of Tissue Regenerative Therapy

The wide variety of laws regulating the research and therapeutic application of stem cells speaks to the ethical conflicts that lie behind the use of these powerful microscopic organisms. For example, the embryos utilised in stem-cell research derive from ovules fertilised in vitro in fertility clinics and were never implanted into a woman’s uterus. Stem cells provided with informed donor consent can live and grow in special solutions in test tubes or Petri dishes in laboratories, and what should be done with the remaining material is one of the great debates of modern ethics.

Even with the scientific use of mature stem cells, which sidesteps the ethical issues surrounding embryos, doubts still arise. The processes whereby cells are reprogrammed into induced pluripotent stem cells have improved enormously, but these cells may be less versatile and last for less time than their embryonic equivalents. Also, they cannot be manipulated to produce all types of cells, which limits their medical benefits. And finally, mature stem cells are more susceptible to environmental dangers like toxins and more prone to error when they duplicate.

The foremost minds in biology and medicine have changed how they speak about the field. They do not use the word “treat”, but rather “regenerate”. This semantic change hints at a novel concept: the possibility to give a body back its vitality and its ability to cure itself through one of its smallest and most powerful components: the stem cell. We are all witnesses – and in all likelihood, beneficiaries of – a great scientific revolution.

© Institute of Tissue Regenerative Therapy

Leaders in Stem-Cell Research and Treatment

Mayo Clinic
Various locations across the US and London

With extensive experience in stem-cell research, Mayo Clinic offers established and experimental therapies, including transplants for various blood diseases and occasionally for autoimmune illnesses like systemic scleroderma and multiple sclerosis. The clinic is also exploring possible applications of CAR-T therapies for malignant, neurological and autoimmune diseases.

Instituto de Terapia Regenerativa Tisular
Barcelona, Spain

The Institute for Tissue Regeneration Therapy’s protocol using cultivated mesenchymal stem cells (connective tissue cells, blood vessels and lymphatic tissue) is a global gold standard. Its 22 clinical trials have managed to demonstrate that only by multiplying cells in a laboratory can the volume required to regenerate tissue for tendons, cartilage (in cases of arthrosis), intervertebral discs, bones (for pseudoarthrosis and osteonecrosis) and saliva glans be achieved.

Stanford Cancer Institute
Palo Alto, California

Stanford’s Cancer Institute combines its investigations into the biology of cancerous cells with scientific developments in the field of stem cells, as well as in genetics, genomics, immunology, immunotherapy and molecular imaging, to create more effective treatments for various kinds of tumours, including Hodgkin’s lymphoma.

Sobajima Clinic
Osaka, Japan

Specialists in using stem cells from adipose tissue to treat osteoarthritis, rheumatoid arthritis and persistent neurological symptoms caused by lumbar and cervical disorders, Sobajima’s treatment has proved effective in relieving chronic pain thanks to its anti-inflammatory, angiogenic and anti-fibrotic effects.

Bioscience Institute Middle East
Dubai, UAE

Founded in Dubai in 2014, Bioscience was the first Regenerative Medicine clinic in the Middle East. Its aesthetic and anti-ageing treatments are among the best in the world, and its therapies using autologous stem cells (harvested from the patient) some of the most advanced. The clinic also offers stem-cell extraction, cell banks, biopsies and transplants.

Swiss Medica Clinic
Belgrade, Serbia

This clinic has developed specific therapies that use stem cells to aid the recovery of patients with arthritis, type 2 diabetes, multiple sclerosis and Parkinson’s disease, as well as those dealing with the aftermath of a stroke. Furthermore, they have successfully developed a mesenchymal stem-cell therapy for children with autism spectrum disorders.

SHA
Spain and Mexico

Both of SHA’s wellness clinics offer regenerative therapies. At the recently opened property on the Riviera Maya, Dr Diego Martínez is head of regenerative medicine and stem-cell therapies and has deep experience using stem cells for chronic inflammation, autoimmune pathologies and more.

Header photo © Stanford Cancer Institute