The idea of regenerating tissue with stem cells is already present in Greek mythology. When Prometheus transgresses the laws of the gods and steals fire, Jupiter condemns him to be tied with a chain while an eagle devours his liver, which regenerates during the night. But it has been in the last twenty years that the possibility of using cells in the treatment of diseases has emerged as one of the greatest advances in medicine in history. Before discussing cell therapy, it is important to define what a stem cell is: when we talk about stem cells, we are referring to cells with two fundamental characteristics: they are capable of generating daughter cells identical to themselves and with the same capacity to proliferate, and at the same time, they are capable of generating differentiated cells, i.e. cells that are different from the cell from which they originate.

In contrast to pluripotent stem cells, obtained from embryos or by reprogramming (as detailed by Dr. Graf in La core topic), we have known for several decades that most organs possess, to a greater or lesser extent, a regenerative capacity associated with the presence of tissue-specific stem cells. The identification of stem cells in the brain or heart, recently described, is allowing us to understand the principles that regulate their capacity to regenerate these tissues. Although cell therapy trials have recently been initiated with iPS or embryonic cells, more than 99% of clinical trials are performed with adult stem cells, so I will restrict my discussion to this subject of cells.

The applications of stem cells are divided into several groups. Firstly, we would find the diseases in which the application of cell therapy is a reality. Bone marrow transplantation, in which hematopoietic stem cells are used to regenerate bone marrow, would be the most established example and has been performed for more than 60 years, with more than 50,000 transplants annually in the U.S. There are other established forms of cell therapy, which do not have the glamour of Parkinson's disease or myocardial infarction, but in which the use of stem cells has proven to be an effective treatment. Although the prevalence is not high in blindness of corneal origin (limbal corneal insufficiency), transplantation of limbal corneal stem cells either from the patient himself or from a donor has produced important clinical results for more than ten years. The technique is not widely disseminated as it requires complex means and experienced medical teams, but it has its application and efficacy. The same could be said of the use of epidermal lamellae developed from the culture of skin fragments and widely used in the treatment of major burns or the use of autologous chondrocytes for the repair of cartilage lesions.

Stem cell therapy poses challenges but also expectations for thousands of patients

There are also diseases in which cell therapy is a treatment with high expectations but whose efficacy has not yet been demonstrated. This is the case of cardiovascular diseases - myocardial infarction, cerebral infarction or peripheral ischemia - where, based on the results of programs of study in animals, clinical trials have been initiated to determine whether these treatments are feasible, safe and effective. In cardiac diseases, stem cells from different sources have been used, comparing standard treatment with stem cell transplantation, with promising results that justify continuing with research in patients in order to define their role in treatments. The employment of stem cells capable of generating insulin-producing cells or restoring neuronal circuits shows great potential. goal Finally, the treatment of other diseases such as Alzheimer's dementia or multiple sclerosis with stem cells is much more distant, or even unrealistic, due to the complexity of the pathophysiology of these diseases, the multiple tissues affected and the complexity of the altered circuits.

One of the essential questions for progress in this field is to understand the mechanism by which stem cells function. Although they can in some cases contribute to tissue regeneration by replacing damaged cells with new ones, several studies have shown that their healing capacity is due to the release of substances that directly or indirectly facilitate endogenous regeneration and repair mechanisms. We have only begun to discriminate some of these mechanisms, but in the near future they will contribute to the development of new therapeutic strategies. The challenges ahead of us are immense but so are the expectations for thousands of patients. But it is essential to maintain scientific rigor and avoid sensationalism in order to avoid generating false expectations and discouraging patients.