Stem cell research is going full steam at UCLA. The latest breakthrough was published online on February 15 online on February 15 in the journal Blood by UCLA researchers at the Orthopaedic Hospital Research Center and Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research. This dramatic discovery in the function of how blood stem cells develop and survive in the body could lead scientists to better understanding and treatment of blood diseases such as leukemia.
The scientists have refined a specific component of mesenchymal (bone marrow) stem cells (MSCs) known as perivascular cells that support the maintenance of hematopoietic (blood) stem and progenitor cells (HSPCs). They note that the research dramatically improves scientists’ capabilities for sustaining ex vivo (outside the body) high-quality HSPCs, which are capable of becoming any kind of blood cell. They found that purified cells, known specifically as CD146+ perivascular cells, a subset of the “mixed bag” of mesenchymal cells commonly used to differentiate HSPCs, shaped a “niche” for HSPCs and sustained them for a far longer time than was possible before in the laboratory. Stem cell researchers are of the opinion that the poor definition of conventional MSCs is responsible for the inconsistent and sometimes inefficient outcomes in early clinical trials. The timely findings by the investigators emphasize the need for a more thorough characterization of MSCs to fully exploit their clinical potential.
The HSPCs supported by the CD146+ cells also maintained their “stemness” or ability to become any type of blood cell for a far longer period. Because of this support, the scientists were able to engraft the cells in immunodeficient mice, which means that they could infuse the HSPCs into mice whose immune systems had been suppressed. The result is that new bone marrow blood cells grew from the HSPCs, which was not possible with HSPCs maintained on unfractionated (unpurified) mesenchymal cells. The investigators note that in the future this ability may be a key to developing treatments for blood and bone marrow diseases in which scientists use the HSPCs to regenerate healthy blood cells. Before this breakthrough, it has been virtually impossible to maintain and “expand” HSPCs outside the human body without compromising their long-term developmental potential.
“The novelty of this research is that we now have well-characterized and prospectively purified ‘feeder’ (stromal or niche) cells for supporting HSPCs,” noted study first author Mirko Corselli. He added, “We have figured out which cells are directly involved in supporting human blood stem cells, and it is possible in the future that the same approach could be used to find the supporting cells for other types of stem cells. This knowledge might help us create future treatments that involve regeneration of healthy blood cells or other tissues to replace diseased or damaged tissue.”
Another valuable discovery from the research was the ability to take CD146+ cells from adipose tissue (fat tissue) to support HSPCs using the same approach and with similar success as with CD146+ cells taken from bone marrow. The discovery indicates that these purified cells support HSPCs regardless of whether the perivascular CD146+ cells came from bone marrow. “Perivascular cells are ubiquitous and might represent the key stem cell support shared by all blood-forming organs,” noted study leader Bruno Péault, UCLA professor of orthopedic surgery and member of the BSCRC and of the Scottish Center for Regenerative Medicine (Edinburgh, UK). He added, “We now want to determine if and how the ability to sustain HSPCs is repressed in tissues that do not form blood, and if it is reactivated during diseases such as leukemia.”
This research was funded by the UCLA Orthopaedic Hospital, department of Orthopaedic Surgery, and Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, as well as the California Institute for Regenerative Medicine, and the European Community FP7 program, through the Reborne project.
The stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research is committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine, UCLA’s Jonsson Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science. To learn more about the center, click on this link.