Credit: Salk Institute
Researchers say they can use induced pluripotent stem cells (iPSCs) to produce large-scale quantities of universal donor platelets.
The team generated megakaryocytes and platelets from iPSCs under feeder-free conditions.
They were able to produce universal platelets by removing a gene essential to expression of the major histocompatibility antigens.
The resulting platelets were functional and behaved like normal human platelets.
The researchers described this method of platelet production, owned by Advanced Cell Technology, Inc., in Stem Cell Reports.
“Unlike other sources of platelets, human induced pluripotent stem cells can be propagated indefinitely, providing a potentially unlimited source of cells for therapeutic purposes,” said Robert Lanza, MD, Chief Scientific Officer at Advanced Cell Technology.
“This study shows that platelets may be produced from [iPSCs] without the need for serum and feeders and, thus, removes potential risks associated with contaminants and pathogens.”
Dr Lanza and his colleagues used a 3-step protocol to differentiate human iPSCs into megakaryocytes and functional platelets in less than 20 days. The method incorporates several discrete intermediate cells, including proprietary hemogenic endothelium-like cells.
The technique allows for long-term storage of megakaryocyte progenitors so they can be available within a few days when needed to produce large quantities of platelets for transfusion.
In addition, by knocking out the β2-microglobulin gene, the researchers were able to generate platelets that are negative for the major histocompatibility antigens.
This suggests the platelets could be transfused into almost any patient, and the method might even prevent platelet refractoriness, according to the researchers.
The team found no major differences in the iPSC platelets and normal human platelets. The iPSC platelets formed aggregates, lamellipodia, and filopodia after activation, just like normal platelets.
Also like normal platelets, the iPSC platelets circulated for at least 8 hours in macrophage-depleted NOD/SCID mice, with a time to reach maximal accumulation of 30 minutes to an hour.
In another murine experiment, iPSC platelets incorporated into a growing thrombus just like normal human platelets, with an average number of 9.0 ± 1.8 platelets per thrombus.
“The platelets generated with our technology are functional and behave like normal human platelets,” Dr Lanza said. “This technology and these results represent an important step towards generating unlimited supplies of universal donor platelets for transfusion.”
