and Krystyn Van Vliet
Mesenchymal stromal cells grown by the researchers Image from Frances Liu
Specially grown mesenchymal stromal cells (MSCs) can improve hematopoietic recovery, according to preclinical research published in Stem Cell Research and Therapy.
Researchers grew MSCs on a surface with mechanical properties similar to those of bone marrow, which prompted the MSCs to secrete growth factors that aid hematopoietic recovery.
When implanted in irradiated mice, these “mechanoprimed” MSCs sped recovery of all hematopoietic lineages and improved the animals’ survival.
“[MSCs] act like drug factories,” explained study author Krystyn Van Vliet, PhD, of the Massachusetts Institute of Technology in Cambridge.
“They can become tissue lineage cells, but they also pump out a lot of factors that change the environment that the hematopoietic stem cells are operating in.”
Dr. Van Vliet and her colleagues noted that MSCs play an important role in supporting, maintaining, and expanding hematopoietic stem and progenitor cells (HSPCs). However, in a given population of MSCs, usually only about 20% of the cells produce the factors needed to stimulate hematopoietic recovery.
In an earlier study, Dr. Van Vliet and her colleagues showed they could sort MSCs with a microfluidic device that can identify the 20% of cells that promote hematopoietic recovery.
However, the researchers wanted to improve on that by finding a way to stimulate an entire population of MSCs to produce the necessary factors. To do that, they first had to discover which factors were the most important.
Analyses in mice suggested eight factors were associated with improved survival after irradiation—IL-6, IL-8, BMP2, EGF, FGF1, RANTES, VEGF-A, and ANG-1.
Mechanopriming
Having identified factors associated with hematopoietic recovery, Dr. Van Vliet and her colleagues explored the idea of mechanopriming MSCs so they would produce more of these factors.
Over the past decade, researchers have shown that varying the mechanical properties of surfaces on which stem cells are grown can affect their differentiation into mature cell types. However, in this study, the researchers showed that mechanical properties can also affect the factors stem cells secrete before committing to a specific lineage.
For the growth surface, Dr. Van Vliet and her colleagues tested a polymer called polydimethylsiloxane (PDMS). The team varied the mechanical stiffness of the PDMS surface to see how this would affect the MSCs.
MSCs grown on the least stiff PDMS surface produced the greatest number of factors necessary to induce differentiation in HSPCs. These MSCs were able to promote hematopoiesis in an in vitro co-culture model with HSPCs.
Testing in mice
The researchers then tested the mechanoprimed MSCs by implanting them into irradiated mice.
The mechanoprimed MSCs quickly repopulated the animals’ blood cells and helped them recover more quickly than mice treated with MSCs grown on traditional glass surfaces.
Mice that received mechanoprimed MSCs also recovered faster than mice treated with factor-producing MSCs selected by the microfluidic sorting device.
Dr. Van Vliet’s lab is now performing more animal studies in hopes of developing a combination treatment of MSCs and HSPCs that could be tested in humans.
The current research was funded by the National Institutes of Health and the BioSystems and Micromechanics Interdisciplinary Research Group of the Singapore-MIT Alliance for Research and Technology through the Singapore National Research Foundation.
The researchers said they had no competing interests.