Cell therapy and Regenerative Medicine

Every day, we are inundated with ideas that are hackneyed wrongly, but also rightly, about new medical approaches. After the mixtures concocted by grandmother, knowledge promoting a better lifestyle, drugs, surgeries performed remotely and computer-assisted, now that the ailments could now be eradicated by treatments based on living cells.

Cell therapy can be defined as an approach which uses a biological product with a therapeutic effect, which product is produced from the preparation of living human or animal cells. In practice, cell therapy consists of the injection of human cells in order to prevent, treat or alleviate a disease.

It’s about repairing damaged tissue with new cells that will help rebuild them. Isolated or cultured cells can be used to repair damaged tissue, or transformed cells to bring various molecules into tissue. The cell types used in cell therapy are differentiated (mature) and functional cells from an organ, precursor cells from stem cells that have already acquired a certain degree of specialization, and stem cells.

What is a stem cell?

A stem cell is a cell which, when dividing, is capable of giving rise to cells engaged in one or more differentiation pathways or to other stem cells to ensure its own renewal. They are divided into two main categories: embryonic stem cells and adult stem cells. Human embryonic stem cells ignite the imagination because of their immortality and unlimited development potential.

They could be an inexhaustible source of specific cells for basic research and transplant therapies. They have the potential to become any type of cell found in the body (about 200 to 300 different types). They originate from an early embryo. These are the cells that raise ethical issues. However, the cells currently used are immortal lines derived from a limited number of embryonic stem cells. There is therefore no need to use new embryos. Adult stem cells are found in many organs of adult people.

The stem cells found in most tissues have often acquired a certain level of specialization and are therefore limited as to the diversity of tissues that they can generate. In 2007, researchers successfully reprogrammed an adult human skin cell into a stem cell similar to embryonic stem cells1,2. These cells are called induced pluripotent stem cells (iPS cells). It is anticipated that they will replace embryonic cells in research. Many applications are envisaged for these cells; the one with the greatest impact would be an alternative to organ and tissue transplants without presenting the rejection problems.

They could also be useful for generating humanized organs in animal models, for evaluating the metabolism of drugs and their toxicity, for the search for new drugs promoting cell survival and growth, for modeling diseases and cancers and finally , to establish models for studying organ development.

However, there are many challenges that must be overcome to enable the use of these iPS cells. We must not only master the culture and use of these cells, but also induce a good transformation of stem cells and develop an efficient injection technique that allows the survival of implanted cells.

All these conditions combined will make it possible to generate cells which function like adult cells, to generate them in sufficient quantity and to ensure the safety of this approach by reducing the risks of tumor formation or of inappropriate function.

What are its limits ?

Among the many avenues in use to assure the health of individuals, cell therapy is probably the most promising avenue. This explains the many examples of cell uses in research projects around the world. In fact, cell therapy has been present in our living environments for a very long time. For more than 50 years, it has been used in particular to treat hematological cancers and other disorders of the blood system.

The first bone marrow transplant was performed by Dr. E. Donnall Thomas in New York in 1956. The patient with leukemia then received a bone marrow transplant from his identical twin, who was healthy. At the same time, the first transplants were performed in France. The practice then gradually spread elsewhere in the world. In 2009, more than 58,000 blood stem cell transplants were performed worldwide. In Quebec, approximately 500 stem cell transplants are performed annually. Differentiated cells are also transplanted to fight cancer cells or to fight infections after a stem cell transplant.

The Maisonneuve-Rosemont Hospital (HMR) proudly highlighted last fall, the first transplant performed within it, 30 years ago. This intervention was at the time the work of pioneers in the field, hematologists Yvette Bonny, Claude Perreault, Jacques Boileau and Michel Lacombe. This application of cell therapy as performed in the cell therapy laboratory at Maisonneuve-Rosemont Hospital, uses blood stem cells also called hematopoietic stem cells. These are the source of all blood cells. They are present in the bone marrow. The first transplants therefore consisted of puncturing the bones and removing them from the bone marrow (spinal aspirations).

This procedure performed in the operating room is long, mobilizes a large medical team and requires the patient’s general anesthesia. In the 1990s, it became possible to use a drug that causes stem cells to detach from the bone marrow, relocate and circulate in the blood. This is called “stem cell mobilization”. The stem cell collection is then done by apheresis technique. This technique involves enriching the blood circulating outside the body to obtain a concentrate of stem cells. Apheresis is performed by a nurse and does not require anesthesia. Finally, blood stem cells are also present in the umbilical cord blood. They are collected at the time of delivery and are frozen, then stored until a need is expressed.

To date, the use of cord blood is limited and more common in children due to the small number of stem cells required for transplantation, but its applications are increasing. For transplantation in adults, the mobilized cells from the blood and obtained by apheresis are mainly used. Less than 10% of transplants are performed with cells taken by aspiration of bone marrow and 1% from cord blood.

Some current research projects in the world

  1. Repair of the heart muscle following an infartus
  2. Repair of articular cartilage following trauma
  3. Regeneration of the cornea in macular degeneration
  4. Treatment of degenerative diseases of the nervous system
  5. Treatment of diabetes
  6. Skin replacement
  7. Repair of vessels
  8. Bone grafting or consolidation to counter bone loss
  9. Alternative to liver transplant
  10. Fight against cancer
  11. Reconstruction of the blood system

Depending on the disease, its stage of development and the patient’s condition, several approaches can be considered to treat blood cancer or a dysfunction of the blood system. When a transplant is necessary, it can be autologous or allogenic. In the case of an autologous or autograft transplant, the patient receives his own stem cells after his cancer cells have been destroyed. In other circumstances, it is necessary to use a healthy donor for the transplant.

This is called an allogeneic transplant or an allograft. If a compatible donor related to the patient is available, the patient will be the first choice. However, since contemporary families have fewer children, transplants involving a compatible sibling are not always possible. Another solution is a transplant with an unrelated compatible donor. In this case, the existence of a donor compatible with the patient in international banks is verified. When there is no unrelated donor, it is also possible to consider a cord blood transplant.

However, the limit of this type of transplant often lies in the number of cells available. The majority of cord blood transplants are currently performed in children. When standard protocols no longer meet the patient’s needs, manipulation of the grafts is often necessary, and it is at this point that clinical studies are required to provide innovative solutions.