Novel harvesting method rapidly produces superior stem cells for transplantation

December 7, 2017, Massachusetts General Hospital
Credit: CC0 Public Domain

A new method of harvesting stem cells for bone marrow transplantation - developed by a team of investigators from the Massachusetts General Hospital (MGH) Cancer Center and the Harvard Stem Cell Institute - appears to accomplish two goals: making the donation process more convenient and less unpleasant for donors and providing cells that are superior to those acquired by current protocols. Results of the team's studies in animal models and humans will appear in the Jan. 11 issue of Cell and are being published online today.

"Our new method of harvesting stem cells requires only a single injection and mobilizes the cells needed in 15 minutes; so in the time it takes to boil an egg, we are able to acquire the number of stem cells produced by the current standard five-day protocol," says Jonathan Hoggatt, PhD, of the MGH Cancer Center)and Center for Transplantation Sciences, lead author of the Cell paper. "This means less pain, time off work and lifestyle disruption for the donor; more convenience for the clinical staff, and more predictability for the harvesting procedure."

Currently, the most common way of harvesting hematopoietic (blood system) stem cells requires donors to receive daily injections of a drug called G-CSF, which induces stem cells to pass from the into the circulation. After five days of injections - which can produce adverse effects ranging from bone pain, to nausea and vomiting, to enlargement or rupture of the spleen - the stem cells are collected through the bone marrow donation process of apheresis, which takes four to five hours. Sometimes more than one apheresis is required to collect enough stem cells, particularly when patients with conditions like multiple myeloma or non-Hodgkin's lymphoma are donating their own cells.

Hoggatt and colleagues at MGH and other institutions have investigated ways to enhance stem cell donation for several years. In a previous collaboration with Louis Pelus, PhD, of Indiana University School of Medicine , senior author of the current study, they found that adding NSAID drugs like aspirin or ibuprofen could double the effectiveness of the standard collection protocol. But since that approach still relied on multiple injections of G-CSF, the team determined that truly significant improvement to stem cell donation required eliminating the need for G-CSF.

In other previous work, Pelus's team had found that a protein called GRO (growth regulated oncogene)-beta induced rapid movement of stem cells from the marrow into the blood in animal models. Initial experiments by the current study's team revealed that GRO-beta injections were safe and well tolerated in human volunteers but had only a modest effect in mobilizing stem cells. As a result, they tried combining administration of GRO-beta with AMD3100, a drug that is already approved to increase stem cell mobilization in combination with G-CSF, and found that simultaneous administration of both drugs rapidly produced a quantity of cells equal to that provided by the five-day G-CSF protocol.

In addition to determining the mechanisms by which combined administration of GRO-beta and AMD3100 produced enough stem cells so quickly, the team found that transplantation with these cells led to faster reconstitution of bone marrow and recovery of immune cell populations in mouse models. The stem cells produced by this procedure also show patterns of gene expression similar to those of fetal (HSCs), which are located in the liver, rather than the bone marrow.

"These highly engraftable hematopoietic stem cells produced by our new strategy are essentially the A+ students of bone marrow stem cells," says Hoggatt. "Finding that they express genes similar to those of fetal liver HSCs, the blood-producing cells you have before birth, suggests that they will be very good at moving into an empty bone marrow space and rapidly dividing to fill the marrow and produce blood. Now we need to test the combination in a clinical trial to confirm its safety and effectiveness in humans."

A principal faculty member at the Harvard Stem Cell Institute and an assistant professor of Medicine at Harvard Medical School, Hoggatt adds that these new, highly engraftable HSCs and the protocol that generated them represent a valuable new scientific tool that could lead to ways of engineering cells that are even better at engrafting and to methods of expanding in the laboratory rather than within the bodies of donors.

"This is an exciting time in marrow transplantation, as the number of diseases that can be treated or possibly even cured is increasing," he says. "With new gene therapy strategies being developed for diseases like sickle cell anemia, beta thalassemia and severe combined immunodeficiency - the 'bubble boy disease' - having enough high-quality, gene-altered can be a key bottleneck. Our ability to acquire highly engraftable HSCs with the GRO-beta and AMD3100 combination should significantly improve and expand the availability of those treatments."

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

More information: Cell (2017). DOI: 10.1016/j.cell.2017.11.003

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 ...

Researchers point way to improved stem cell transplantation therapies

September 7, 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 ...

Study shows adipose stem cells may be the cell of choice for therapeutic applications

February 24, 2017
An international team of researchers, funded by Morris Animal Foundation, has shown that adipose (fat) stem cells might be the preferred stem cell type for use in canine therapeutic applications, including orthopedic diseases ...

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.

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.

New way to harvest stem cells better for donors

March 15, 2016
Australian scientists have developed a new method for harvesting stem cells, which is less invasive and reduces side effects for donors.

Recommended for you

DNA gets away: Scientists catch the rogue molecule that can trigger autoimmunity

February 22, 2018
A research team has discovered the process - and filmed the actual moment - that can change the body's response to a dying cell. Importantly, what they call the 'Great Escape' moment may one day prove to be the crucial trigger ...

Low-calorie diet enhances intestinal regeneration after injury

February 22, 2018
Dramatic calorie restriction, diets reduced by 40 percent of a normal calorie total, have long been known to extend health span, the duration of disease-free aging, in animal studies, and even to extend life span in most ...

Fertility breakthrough: New research could extend egg health with age

February 22, 2018
Women have been told for years that if they don't have children before their mid-30s, they may not be able to. But a new study from Princeton University's Coleen Murphy has identified a drug that extends egg viability in ...

Artificial intelligence quickly and accurately diagnoses eye diseases and pneumonia

February 22, 2018
Using artificial intelligence and machine learning techniques, researchers at Shiley Eye Institute at UC San Diego Health and University of California San Diego School of Medicine, with colleagues in China, Germany and Texas, ...

Therapy for muscular dystrophy-caused heart failure also improves muscle function in mice

February 22, 2018
Injections of cardiac progenitor cells help reverse the fatal heart disease caused by Duchenne muscular dystrophy and also lead to improved limb strength and movement ability, a new study shows.

Gut microbes protect against sepsis—mouse study

February 22, 2018
Sepsis occurs when the body's response to the spread of bacteria or toxins to the bloodstream damages tissues and organs. The fight against sepsis could get a helping hand from a surprising source: gut bacteria. Researchers ...

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.