UCLA researchers identify specific cell compartment supporting blood stem cells with dramatic results

Feb 15, 2013 Research

UCLA researchers at the Orthopaedic Hospital Research Center and Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research (Broad Stem Cell Research Center or BSCRC) led by Bruno Péault, UCLA professor of orthopedic surgery and member of the BSCRC and of the Scottish Center for Regenerative Medicine (Edinburgh, UK), have refined a specific component of mesenchymal (bone marrow) stem cells (MSCs) called perivascular cells that support the maintenance of hematopoietic (blood) stem and progenitor cells (HSPCs), dramatically improving scientists’ capabilities for sustaining ex vivo high-quality HSPCs, which are capable of becoming any kind of blood cell. 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 study was published online ahead of press today in Blood.

The scientists 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. The general consensus is that the poor definition of conventional MSCs is responsible for the inconsistent and sometimes inefficient outcomes in early clinical trials. The timely findings by Péault’s group 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, meaning they could infuse the HSPCs into mice whose immune systems had been suppressed and new bone marrow blood cells grew from the HSPCs, which was not possible with HSPCs maintained on unfractionated (unpurified) mesenchymal cells. In the future this ability may be key to developing treatments for blood and bone marrow diseases in which scientists use the HSPCs to regenerate healthy blood cells, knowing that so far 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,” said Mirko Corselli, first author on the study, “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 surprising 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,” said Péault, “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 work 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.

Stem Cell Biology