Stem Cell Program | Treatments

Currently, blood stem cells are the only type of adult stem cell used regularly for treatment — they have been used since the late 1960s in the procedure now commonly known as bone marrow transplant. Transplants of neural stem cells have been tried in small numbers of patients with brain disorders such as Parkinson disease, as well as a recently-approved a clinical trial of neural stem cells for spinal cord injury.

Preliminary research in animals has found that bone marrow stromal cells injected into a damaged heart can have beneficial effects. Researchers at Boston Children's Hospital have shown that those same cells injected into the blood of a mouse model can help protect against chronic lung disease in premature newborns.

In some cases, it may be possible to infuse the stem cells into the blood, as in a bone marrow transplant. The cells find their own way to the proper location and begin forming the cells and tissues needed. In other cases the cells may need to be injected directly into the organ or tissue that needs them.

The overall goal is for these cells to be placed into the proper places in the body, divide repeatedly and form functioning tissues, or repair diseased tissue. Outcomes are not always clear — in some cases, the transplanted cells may become part of the tissue or organ, in others they may secrete growth factors that stimulate cells already residing there.

What makes a stem cell into an effective treatment?

In order for a stem cell to be considered a viable part of a treatment plan, it must:

• Reproduce in large enough quantities to provide the amounts needed for treatment. Some adult stem cells have a very limited ability to divide, making it difficult to multiply them in large numbers. Scientists around the world are trying to find ways of encouraging them to multiply. The Stem Cell Program at Boston Children’s Hospital, for example, recently discovered that a drug called PGE2 can multiply numbers of blood stem cells. PGE2 is now being tested in patients with leukemia and lymphoma to see if it will help them rebuild their blood systems.

• Create the needed cell types, either in the laboratory or after they’ve been transplanted into the body.

• Be safe. A host of clinics around the world offer supposed stem-cell therapies with claims of complete success, but these treatments must still be considered experimental and potentially risky until much more work is done to ensure their safety. For example, when adult stem cells are provided from a donor, precautions must be taken to avoid rejection by the patient’s immune system. Unless the patient is his or her own donor, or unless a donor is found with an identical tissue type, the patient will need to take powerful drugs to suppress the immune system so the transplanted cells or tissues won’t be rejected. In addition, if adult stem cells are manipulated incorrectly, there is a risk of cancer.

• Stay alive and remain functional for the rest of the patient’s life, continuing to maintain a healthy tissue or organ.

Turning pluripotent stem cells into treatments 

If reliable techniques are developed, pluripotent stem cells could allow doctors to create customized, rejection-proof transplants to treat a scarred heart, damaged nerves or compromised immune systems. This can be achieved by obtaining pluripotent stem cells that match the patient genetically via genetic reprogramming, nuclear transfer, or parthenogenesis.

Critical steps to developing the cells

Developing cells include the following steps:

• Grow the pluripotent stem cells in culture to create a large quantity of stable, healthy cells.
• Repair faulty genes. This step would be needed if the cells carry a genetic disorder, such as sickle cell anemia.
• Turn the stem cells into a specific cell type or tissue. Once a stable, genetically healthy line of pluripotent cells is established, they must be coaxed into creating specialized types of cells. This process is called differentiation. In nature, it happens through a complex mix of physical and chemical signals, and researchers are learning how to copy these signals in the laboratory.
• Transplant the cells or tissue to the diseased/damaged organ or tissue. The cells will need to reach the right part of the body, take hold, and begin to function. Scientists know how to deliver blood stem cells — through bone marrow transplant — but they still need to develop effective delivery methods for other cell types.

Getting the pluripotent stem cells

Right now, it’s not clear what will ultimately be the source of pluripotent stem cells used to create treatments, because none of the techniques currently being studied have yet moved into the clinic. The cells can be made in one of several ways:

• Nuclear transfer: Using a patient’s skin cell, transferred into an egg
• Genetic reprogramming: Transforming a skin cell, blood cell or other cell from the patient into a pluripotent stem cell
• Parthenogenesis: Using unfertilized eggs. A donor might be able to use their own eggs to create stem cells that match them genetically or draw on master banks of stem cells made from eggs

How are adult stem cells turned into treatments?

Currently, blood stem cells are the only type of adult stem cell used regularly for treatment. They have been used since the late 1960s in the procedure now commonly known as bone marrow transplant. Transplants of neural stem cells have been tried in small numbers of patients with brain disorders such as Parkinson’s disease, and the FDA recently approved a clinical trial of neural stem cells for spinal cord injury.

Preliminary research in animals has found that bone marrow stromal cells, injected into a damaged heart, can have beneficial effects. And researchers at Boston Children’s have shown in a mouse model that the same cells, injected into the blood, help protect against chronic lung disease in premature newborns.

In some cases, it may be possible to infuse the stem cells into the blood, as in a bone-marrow transplant. The cells find their own way to the proper location and begin forming the cells and tissues needed. In other cases, the cells may need to be injected directly into the organ or tissue that needs them.

The ultimate goal is for the cells to take up residence in their proper places in the body, divide repeatedly and form functioning tissues — or repair diseased tissue (though it is not always clear how this happens). In some cases, the transplanted cells may become part of the tissue or organ. In others, they may secrete growth factors that stimulate cells already residing there.

For adult stem cells to be successful treatments, they must:

• reproduce in large enough quantities to provide the amounts needed for treatment
• create the needed cell types, either in the laboratory or after they’ve been transplanted into the body
• be safe (incorrectly manipulated stem cells can develop the potential to form cancer)

What is the latest research on adult stem cells from Boston Children’s?

Boston Children's has achieved a number of milestones in adult stem cell research. Its researchers were the first to:

• isolate lung stem cells, both in normal lungs and in lung cancer — more recently, to reproduce the very initial steps of lung cancer using mini-lung organs grown in a dish
• create hematopoietic stem cells and other blood products from human pluripotent cells
• regenerate liver from transdifferentiated liver progenitor cells
• identify a type of heart progenitor that forms at least two main cell types in the heart
• demonstrate a way to boost numbers of stem cells in the laboratory, using a drug called PGE2 to increase production of blood stem cells
• take a drug from stem cell research into clinical trials with the aim of helping patients with leukemia and lymphoma

A large effort, involving many labs at Boston Children’s, is being devoted to understanding the cues that coax stem cells to divide and multiply, transform into specialized cell types, migrate to other parts of the body, and become a functioning part of tissues. Understanding these cues will help in designing more effective cell-based treatments. Within the Stem Cell Program, an innovative new study is following the live workings of adult stem cells in the body to understand how they behave day-to-day in maintaining tissues.

Other ongoing research in adult stem cells includes:

• investigation of stem cells in the small intestine, kidney, and other organs
• using stem cells from umbilical cord blood to build muscle in muscular dystrophy
• using stem cells from the amniotic fluid to create tissue-engineered implants for babies with birth defects
• using progenitor cells isolated from blood and muscle to build heart valves, blood vessels and electrically conductive tissue for the heart

What are progenitor cells?

Often confused with adult stem cells, progenitor cells are early descendants of stem cells that can differentiate to form one or more kinds of cells but cannot divide and reproduce indefinitely. A progenitor cell is often more limited than a stem cell in the kinds of cells it can become. Nonetheless, progenitor cells do have potential uses in medicine. Boston Children’s Hospital researchers, for example, are studying the potential of blood and muscle progenitor cells in building heart valves, as well as blood vessels and electrically conductive tissue for the heart. Research from the Camargo Lab has found that progenitors can behave like stem cells for much longer than anticipated as long as they are not removed from their tissue of origin. This research has opened up the possibility of using progenitor cell therapy in the bone marrow, and it also provides an understanding for how progenitors may be at the origin of cancer and other blood diseases.