[LUM#6] The Restored Body

Replacing damaged or diseased cells with healthy ones… That is the principle behind cell therapy. It finally offers hope for a complete cure: the new frontier of21st-century medicine.

A promising tool for cell therapy: induced pluripotent stem cells, generated in the laboratory from specialized adult cells. © Bai Qiang, John De Vos team

There was surgery. And medication. A new frontier in medicine has been emerging over the past few decades: cells. The principle of cell therapy is to implant healthy cells into a patient to replace damaged tissue. Its applications? Potentially endless. Cancers, neurodegenerative diseases, cell-destructive conditions such as diabetes, heart attacks, osteoarthritis…“Thanks to cells, we can envision completely curing conditions that are incurable by other means,” explains John De Vos, head of the cell therapy unit at Montpellier University Hospital and a researcher at the Institute of Regenerative Medicine and Biotherapy.

Some cell therapies are already well-established and used on a daily basis. Their primary tool? Adult stem cells, which are found within our organs and are specialized, capable of producing the various cell types of the organ to which they belong. These cells are therefore responsible for repairing and renewing our tissues throughout our lives. For example, skin stem cells, once harvested and cultured, can yield an epidermal surface area up to a thousand times larger… Enough to treat severe burn victims with their own skin, without the risk of rejection.

Transplanting a new immune system

For decades, one of the most well-established cell therapies has relied on blood stem cells—the cells that produce blood cells. Known as hematopoietic stem cells (HSCs), they play a fundamental role in treating blood cancers. Injecting a sufficient quantity into a patient is equivalent to transplanting a new immune system… This has a dual effect: the graft recognizes and destroys the cancer. And it replaces the original immune system, which has been damaged by treatments.

But where can these precious blood-producing cells be obtained? Either from the bone marrow of compatible donors—anonymous donations from international registries or family members—or from placental blood. To do this, blood is collected from the umbilical cord of newborns whose parents have given their consent. Each frozen graft is added to a placental blood bank and then registered in internationally coordinated registries… This enables patients around the world to obtain the compatible graft that could save their lives.“There are people in Turkey, the Netherlands, the United States, and Germany who are living with blood from a child born in Montpellier. The placental blood bank at the UTC in Montpellier now holds 2,500 units of placental blood,” explains John De Vos.

HSCs can also be injected back into the patient themselves, in a procedure known as an autologous transplant. Before particularly intensive chemotherapy, HSCs are collected from a patient with lymph node cancer. After treatment, they are reinfused into the patient… allowing their immune system to regenerate.

Spectacular healings

Another cell therapy has proven highly effective: treating diabetes using specialized pancreatic cells. These cells produce the insulin that allows us to regulate our blood sugar levels.“Some patients with very severe and unstable diabetes who have been living with the condition for decades can thus stop insulin injections completely, at least for a while ,explains John De Vos. This powerful treatment is only a fraction of the solution to this disease. In particular, it cannot be widely implemented: it would require far too many deceased donors…

Skin regeneration, treatment of blood cancers or severe diabetes… these cell therapies are already well established. What about the therapies of the future? A rapidly evolving field, immunotherapy involves treating patients with certain blood cancers by harvesting cells crucial to the immune system: lymphocytes. These cells are genetically modified to teach them to recognize cancer… before being re-injected into the patient. The results of clinical trials: spectacular cures for children with acute leukemia resistant to all treatments. “In cohorts where 100% of patients appeared doomed, the majority were saved. It’s very rare to see such a breakthrough in the treatment of a disease,” enthuses John De Vos.

Regenerate any tissue

The revolutionary frontier of cell therapy ultimately also lies in the famous pluripotent stem cells (Demain guérir LUM No. 2). Immature and undifferentiated, they are capable of producing any type of cell in the body. They are found naturally in embryos about one week old, which measure one-tenth of a millimeter… And in recent years, research has taught us how to obtain them by reprogramming mature adult cells. The next step is to induce them to differentiate before injecting them. And to potentially see them regenerate any tissue or organ in the body (Induced Pluripotent Stem Cells: A New Paradigm for the Study of Human Tissues, in Biologie aujourd’hui, 2016).

This research still requires years of development. The biggest challenge at the moment remains the injection process.“We haven’t yet mastered the injection technique; the injected cells don’t necessarily find their way into solid tissues,” explains John De Vos. “Each organ has its own injection challenges: for example, how do we ensure that neurons intended to treat Parkinson’s disease project their axons to the right location? Stem cell research, which is extremely promising, will advance and will undoubtedly find solutions on an organ-by-organ basis.”

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