New Hope for Safer Treatments

in Stem Cell Transplantation

New research shows that stem cell transplantation without radiation and chemotherapy may be possible, making cancer treatments easier, safer and more accessible to a broader range of patients.

This procedure can save the lives of patients with cancer, especially patients with immune or blood disorders, such as leukemia and lymphoma. The procedure, however, is not always tolerated by some patients and is potentially dangerous due to chemotherapy and/or radiation treatments prior to transplantation. For this reason, researchers have been searching for new methods to grow large numbers of hematopoietic stem cells in the laboratory, to make stem cell transplantation easier and safer. While many attempts have been made over the years, only recently researchers from Stanford and The University of Tokyo seem to have found a way to grow large numbers of hematopoietic stem cells in the lab and even perform stem cell transplants without using chemotherapy or radiation.

What is stem cell transplantation?

For some time, people with immune or blood disorders have been cured with a transplant of healthy hematopoietic stem cells, which can be collected from the patient’s own body (autologous transplants), from a donor (allogeneic transplants) or even from an identical twin (syngeneic transplants). Hematopoietic stem cells can come from bone marrow, peripheral blood or the umbilical cord of a newborn baby. Stem cells can divide to make more hematopoietic stem cells or develop into different types of blood cells. Stem cell transplantation is done to replace stem cells that have been damaged or destroyed by disease, cancer or by high doses of chemotherapy or radiation therapy.

When a stem cell transplant takes place, new stem cells are placed in the body, they settle in the bone marrow and begin to grow and make new healthy cells. This process of regeneration is called engraftment. Stem cell transplants may be used to treat some cancers such as leukemia, lymphoma, multiple myeloma and neuroblastoma. While there are several types of stem cell transplants, each have different risks and complications and most use some form of chemo and/or radiation in different doses.

Stem Cell Transplant

Why radiation and chemotherapy are used in stem cell transplantation

Stem cell transplantation has cured many people, yet in order for this treatment to work, the patient’s own hematopoietic stem cells must be killed first, in order to eliminate the disease and allow the healthy cells to settle in the bone marrow when transplanted. The process of killing unhealthy cells is called conditioning and includes chemotherapy, radiation or both. The problem with conditioning is that it also kills healthy stem cells in the bone marrow and can cause life-threatening side effects such as infections, respiratory problems and organ damage. Young patients can even suffer side effects such as growth retardation, infertility and secondary cancer later in life. Some patients cannot receive transplants because they are either too old or too sick. For this reason, researchers have been trying for decades to find a way to grow large numbers of hematopoietic stem cells in the lab so they could be reintroduced into the body without the need for conditioning.

A breakthrough in safer stem cell transplants

Two teams of researchers from the University of Tokyo and Stanford University in California, led by stem-cell biologist Hiromitsu Nakauhi, MD, PhD, professor of genetics at Stanford, have made a breakthrough in stem cell transplantation. Until now, lab experiments were never able to produce a number of hematopoietic blood stem cells large enough to begin producing healthy new blood cells when transplanted into the body. Nakauhi’s team, however, showed for the first time that hematopoietic stem cells from mice could reproduce hundreds or even thousands of times in just 28 days. Research results were published in the journal Nature on May 29.

After expanding a cluster of hematopoietic mouse blood cells to almost 900 times its original level in just one month, researchers successfully transplanted them back into different mice, where they renewed and produced many new cells. Nakauhi suspects the cells thrived because of the large number transplanted into the mice. “This has been one of my life goals as a stem cell researcher,” said Nakauhi. “For 50 years, researchers from laboratories around the world have been seeking ways to grow these cells to large numbers. Now we’ve identified a set of conditions that allows these cells to expand in number as much as 900-fold in just one month. We believe this approach could transform how hematopoietic stem cell transplants and gene therapy are performed in humans.”

The researchers were also able to successfully transplant large numbers of the cells into mice without killing stem cells first. Thus, they were able to perform transplantation without conditioning. If this technique proves successful in humans, by generating a large number of stem cells in the lab, patients would be able to use their own stem cells without relying on donors and could avoid chemotherapy and/or radiation prior to transplantation. By reducing the need for conditioning, these treatments would become safer and accessible to more patients. Furthermore, the study showed that researchers may be able to use gene-editing tools and correct disease-causing mutations before transplanting the cells back in patients. “We also found that, during the culture, we can use CRISPR technology to correct any genetic defects in the original hematopoietic cells,” Nakauchi said. “These gene-corrected cells can then be expanded for transplantation. This should allow us to use a patient’s own cells as gene therapy.”

Nakauchi and his team of researchers are now testing this approach in mice. The next step is to begin testing on humans, yet the results of the study show that there are new ways stem cell transplants can be performed, offering safer alternatives for the future.

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