Stem cell therapy

Although research is ongoing for many novel stem cell therapy techniques that have shown varying degrees of promise for clinical application, only a select few are approved for medical use as of now by the FDA (Food and Drug Administration, USA). Another important tenet of stem cell therapy is its ethical implications. The ability to artificially modify the genetic properties of cells to clone them has been contested as an unethical practice by many institutions. Therefore, stem cell therapy research and use are kept in check with stringent regulations by the competent and relevant bodies concerned. The only modality of stem cell therapy currently approved by the FDA (Food and Drug Administration, USA) for clinical use is hematopoietic stem cell (HSC) transplantation and it is permissible for limited use in select blood disorders and cancers that are listed by the Food and Drug Administration (FDA). A hematopoietic stem cell transplant is also referred to as a bone marrow transplant. 

• Hematopoietic stem cell transplantation procedures: It is the only approved type of stem cell therapy and is used to treat rare disorders of the blood and some types of blood cancers. While the stem cells to be used for therapy can also be retrieved from cord blood (collected and preserved at the time of birth), most are harvested from the bone marrow. In principle, the stem cells harvested, usually from bone marrow or cord blood, are transfused (transplanted) into the patient’s body where they go settle in the bone marrow and produce new healthy blood cells like red blood cells (erythrocytes), white blood cells (leukocytes) and platelets (thrombocytes). These treatments are quite gruelling, last for several weeks and consist of intensive chemotherapy (stronger than regular chemotherapy used for cancer as the aim is to kill off the dysfunctional bone marrow to be replaced) followed by stem cell infusions. Nursing care and prolonged hospital admissions may be necessary to closely monitor the patient undergoing therapy. At the moment, stem cell transplantation procedures are quite expensive.
• Other ongoing research: With the advent of technology that allows the creation of induced pluripotent stem cells from regular adult stem cells, many new avenues for clinical research on novel techniques have emerged. Earlier it was thought that only blood cells could be regenerated from stem cell therapy (as with HSC) but now research has shown potential for the treatment of neurological and neurodegenerative conditions, diabetes mellitus and cardiovascular diseases amongst others. A recent clinical trial focused on stem cell therapy for bad knees (or osteoarthritis). Although the results are only preliminary, it was found that stem cell therapy could prevent the progression of the condition. Stem cell therapy research today involves not only the transplantation of new stem cells but also the use of stem cell-derived products for the management of ailments. However, it is important to remember that these modalities are experimental treatments and need many years of safety testing and regulatory checks before they’re made available to the general public.

Stem cell therapy can be needed in cases where a patient’s bone marrow is damaged or dysfunctional following cancer chemotherapy, chronic infections or other diseases. These procedures are usually reserved as last resorts and other treatment options are tried first. Possible reasons for HSC transplantation to be recommended can be:

• Haematological or blood disorders like: 
  • Aplastic anaemia
  • Sickle cell disease 
  • Thalassemia
  • Congenital neutropenia 
• Cancer affecting the bone marrow like:
  • Leukaemia 
  • Lymphoma 
  • Multiple myeloma 
• Post cancer chemotherapy: The bone marrow can become damaged and diseased. 
• Immunological 
  • Severe Coupled Immunodeficiency (SCID): It is a rare genetically-inherited disease in which the patient’s body is unable to form T-cells and B-cells that mediate immunity. Such children can succumb to the most inane infections and usually the only treatment possible is a bone marrow transplant. 

(Read more: Blood cancer)

There are two main types of stem cell transplants:

• Autologous transplant: Sometimes, cells are harvested from the patient themselves before starting a damaging therapeutic regimen like chemotherapy or radiotherapy. After the treatment has been completed, the harvested and preserved cells are returned to the patient. Although not always available, this type of stem cell transplant significantly reduced the risk of transplant failure and graft versus host disease (GVHD). 
• Allogenic transplant: In diseases where the patient’s bone marrow and stem cells are not healthy enough to function properly, stem cells are harvested from a donor who is a close genetic match. The donor can be a close familial relation or an unrelated individual who is a close genetic match. In such cases, the patient has to first be subjected to immunosuppressive medications (intensive chemotherapy) to kill off the bone marrow to be replaced and prevent immunological rejection of the donor cells. Stem cells can be collected from: 
  • Bone marrow: Stem cells are collected from within the space inside the bone that holds the marrow. This is commonly done with a small operative procedure at the pelvic bone of the donor.
  • Blood: Usually, stem cells are present inside the marrow but a small fraction can be found in the blood as well. In order to harvest cells for a transplant, medicines are given to donors for a few days to stimulate overproduction and overflow of cells into the bloodstream. Following this, the donor’s arm is hooked on to a cell separator machine that collects marrow cells from the blood over 4 to 6 hours. 
  • Cord blood: Stem cells are collected from the blood present in the umbilical cord of a baby while cord clamping at birth. 

(Read more: What it means to be immunocompromised)

Things to note about the procedure of stem cell therapy: 

• Before transplantation: The patient will be subjected to genetic tests to find out what type of bone marrow stem cells they require. The donor stem cells should be the closest possible genetic match to the recipient’s. After this, they would be subjected to intense chemotherapy that will kill off the defective bone marrow (which is to be replaced) and prevent immunological rejection of the new host stem cells. This is a gruelling and taxing process during which the patient is more susceptible to infections and is usually housed in a special area of the hospital to protect them.
• During transplantation: After chemotherapy, harvested stem cells are transfused into the patient’s bloodstream via an intravenous drip. This procedure is similar to that of a blood transfusion. It takes several weeks for the reactivation of the marrow and repeated transfusions are necessary. During this time, the immunosuppressed patient is monitored closely at the hospital and antibiotics are given to prevent infections.
• After transplantation: Engraftment refers to the successful uptake and functioning of the new bone marrow cells after hematopoietic stem cell (HSC) transplantation. The first sign of engraftment is a rising white blood cell count, which can take place anywhere between 10 days to a month following the first transfusion.

Hematopoietic stem cell (HSC) transplantation is a major medical intervention and, as with all major procedures, is associated with some transient complications. Certain risk factors increase the patient’s susceptibility to developing complications following the procedure. Factors can be the patient’s age, overall health status, the type of disease being treated and the type of bone marrow transplant being received. Transient clinical signs and symptoms can include but may not be limited to:

• Fall in blood pressure
• Headaches
• Nausea
• Pain
• Shortness of breath
• Chills
• Fever

While the aforementioned signs and symptoms immediately following the procedure abate shortly, some more pressing complications can arise later. These may range from mild to severe. Following HSC transplantation, there exists a risk for the development of the following complications:

• Graft Versus Host Disease (GVHD): After an allogeneic bone marrow transplant, the donor cells may view the recipient's cells as foreign (if the HLA compatibility is not an exact match) and launch an immune attack on them.
• Transplant failure: In some cases, the recipient’s body may not recognise and accept the transplanted stem cells as its own and can lead to rejection of the transplantation.
• Organ damage: Following a transplant failure, organs may become damaged. 
• Bleeding: Due to lack of platelets following intensive chemotherapy and preceding the stem cell transplantation, bleeding can occur in the lungs, brain or other parts of the body.
• Infections: Following intense chemotherapy, the body’s immunity is weakened (weak immune system) and many infections can be contracted that may become life-threatening. Antibiotics are usually taken for a few weeks following the procedure for prevention.
• Anaemia: Suppression of the bone marrow with chemotherapy preceding stem cell transfusion can lead to dwindling red blood cell population and resultant anaemia. 
• Mucositis: Inflammation, with soreness and redness, of mucosal lining membranes of the mouth, throat and stomach.
• Cataract: Following bone marrow transplantation, posterior subcapsular cataracts may arise in the eyes. This is a rare complication, generally does not require surgery and is dependent on the dose of immunosuppressive steroids administered.