Researchers point way to improved stem cell transplantation therapies

September 7, 2017
When transiently expressed in HSCs, BCL-XL temporarily protects the cells from apoptosis and enhances their ability to be transplanted from one mouse to another. This microscopy image shows the successful introduction of BCL-XL (green) into a cell labeled for its nucleus (blue) and mitochondria (red). Credit: Kollek et al., 2017

Researchers in Germany have demonstrated that hematopoietic stem cell (HSC) transplants can be improved by treatments that temporarily prevent the stem cells from dying. The approach, which is described in a paper to be published September 7 in The Journal of Experimental Medicine, could allow those in need of such transplants, including leukemia and lymphoma patients, to be treated with fewer donor stem cells while limiting potential adverse side effects.

HSCs give rise to the many different cell types found in blood and can be used to treat a variety of diseases, including multiple myeloma, leukemia, and blood disorders such as . HSCs can be harvested from a suitable donor and then transplanted into a patient, where, after establishing themselves in the , they can generate healthy .

The transplantation process is stressful for HSCs, however, and many of them die before they can successfully ensconce themselves in the patient's bone marrow. This limits the effectiveness of HSC transplantation, delaying the resumption of blood cell formation—increasing the risk of infection or bleeding—or even causing the to fail completely. HSC death is a particular problem if the number of donor is low to begin with. Umbilical cord blood, for example, generally contains insufficient numbers of stem cells for it to be used as a source of HSCs for transplantation into adult patients.

HSCs die through a process called apoptosis, driven by two proteins called BIM and BMF. Permanently inhibiting these two proteins prevents HSCs from dying and improves the efficiency of HSC transplantation in mice. But mice receiving these apoptosis-resistant stem cells soon develop autoimmune disease and/or lymphomas because the HSCs, and the blood cells they produce, do not die when they are supposed to.

"Thus, inhibiting apoptosis transiently during the stressful period of transplantation could be an attractive strategy to improve transplantation outcome without increasing the risk of long-term adverse effects," says Dr. Miriam Erlacher of the University Medical Center of Freiburg.

Erlacher and colleagues isolated HSCs from mice and infected them with a genetically engineered adenovirus that transiently produces a human protein called BCL-XL that inhibits BIM and BMF. These virally infected HSCs were resistant to apoptosis for the 7-9 days that BCL-XL was expressed, and, upon transplantation into recipient mice, their ability to establish themselves in the bone marrow and produce new cells was greatly enhanced. Moreover, because the transplanted HSCs only expressed BCL-XL for a few days, they didn't promote the formation of lymphomas in recipient animals.

Adenoviral infection is slightly toxic to HSCs, however, so Erlacher and colleagues developed an alternative approach in which purified BCL-XL could be introduced directly into isolated HSCs. This second method also provided temporary protection from apoptosis and improved the cells' ability to undergo transplantation.

"Our findings suggest that transiently inhibiting apoptosis by manipulating donor HSCs increases the fitness of these without elevating the risk of adverse pathology," Erlacher says. "Transient apoptosis inhibition is therefore a promising approach to reduce the risk of graft failure and improve HSC transplantation outcomes."

Explore further: Dose of transplanted blood-forming stem cells affects their behavior

More information: Kollek et al., 2017. J. Exp. Med. jem.rupress.org/cgi/doi/10.1084/jem.20161721

Related Stories

Dose of transplanted blood-forming stem cells affects their behavior

May 25, 2016
Unlike aspirin, bone marrow doesn't come with a neatly printed label with dosage instructions. However, a new study published in Cell Reports provides clues about how the dose of transplanted bone marrow might affect patients ...

Changing the environment within bone marrow alters blood cell development

February 22, 2017
Researchers at the University of Illinois report they can alter blood cell development through the use of biomaterials designed to mimic characteristics of the bone marrow.

Out of body experience for stem cells may lead to more successful transplants

August 4, 2011
New research finds that growing blood stem cells in the laboratory for about a week may help to overcome one of the most difficult roadblocks to successful transplantation, immune rejection. The study, published by Cell ...

Blood stem cells study could pave the way for new cancer therapy

March 10, 2016
People with leukaemia could be helped by new research that sheds light on how the body produces its blood supply.

Scientists wage fight against aging bone marrow stem cell niche

March 2, 2017
As people get older so do the hematopoietic stem cells (HSCs) that form their blood, creating an increased risk for compromised immunity and certain blood cancers. Now researchers are reporting in the scientific journal EMBO ...

Researchers poke around for blood genes

July 10, 2015
Even though the transplantation of blood stem cells, also known as bone marrow, has saved many lives over many decades, the genes that control the number or function of blood stem cells are not fully understood. In a study ...

Recommended for you

Researchers find way to convert bad body fat into good fat

September 19, 2017
There's good fat and bad fat in our bodies. The good fat helps burn calories, while the bad fat hoards calories, contributing to weight gain and obesity. Now, new research at Washington University School of Medicine in St. ...

New model may help science overcome the brain's fortress-like barrier

September 19, 2017
Scientists have helped provide a way to better understand how to enable drugs to enter the brain and how cancer cells make it past the blood brain barrier.

Cell-based therapy success could be boosted by new antioxidant

September 19, 2017
Cell therapies being developed to treat a range of conditions could be improved by a chemical compound that aids their survival, research suggests.

Study suggests epilepsy drug can be used to treat form of dwarfism

September 19, 2017
A drug used to treat conditions such as epilepsy has been shown in lab tests at The University of Manchester to significantly improve bone growth impaired by a form of dwarfism.

Research predicts how patients are likely to respond to DNA drugs

September 19, 2017
Research carried out by academics at Northumbria University, Newcastle could lead to improvements in treating patients with diseases caused by mutations in genes, such as cancer, cystic fibrosis and potentially up to 6,000 ...

Urine output to disease: Study sheds light on the importance of hormone quality control

September 18, 2017
The discovery of a puddle of mouse urine seems like a strange scientific "eureka" moment.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.