Hematopoietic Stem Cell Sorting: Keeping it Simple with a CD11a and EPCR Combination

Review of “The CD11a and Endothelial Protein C Receptor Marker Combination Simplifies and Improves the Purification of Mouse Hematopoietic Stem Cells” from STEM CELLS Translational Medicine by Stuart P. Atkinson

While high cell purity promotes successful hematopoietic stem cell (HSC) transplantation outcomes, current cell sorting approaches require numerous and somewhat unreliable cell markers. Researchers from the laboratory of Matthew A. Inlay (University of California Irvine, USA) responded for the need for a more simple HSC sorting strategy by demonstrating that while most cells of the hematopoietic lineage express CD11a (integrin alpha L or Itgal), HSCs themselves lack the expression of this marker [1]. 

Now, in a new STEM CELLS Translational Medicine study, the Inlay laboratory returns with a new study describing a simple new approach to HSC sorting using combination of CD11a with EPCR (endothelial protein C receptor or CD201) [2] that may boost transplantation outcomes. 

Initial experiments employed CD11a- EPCR+ to re-sort the “KLS” hematopoietic cell population, known to contain all hematopoietic stem and multipotent progenitor cells (HSPCs), revealing a distinct population with increased HSC activity including primary and secondary engraftment following transplantation into lethally irradiated adult mouse recipients. Furthermore, CD11a– EPCR+ sorted HSPCs directly outcompeted CD11a+ HSPCs in a competitive transplantation assay and provided a more balanced lineage distribution.

Interestingly, the combination of CD11a- EPCR+ also provided for an enriched HSC population from previously unsorted blood; although at a lower HSC purity when compared to the CD11a- EPCR+ KLS cell population (which uses many more markers). However, HSC purity following CD11a– EPCR+ sorting compared well to the successful SLAM strategy of sorting HSCs employing only CD150+ CD48- sorting [3].

The authors suggest that CD11a- EPCR+ sorting provides a simple, cost-effective, and efficient means for sorting mouse HSCs to allow in‐depth molecular and functional characterization. However, the authors do note that while they did not address CD11a expression on human HSCs, one study has employed EPCR to purify in vitro expanded human HSCs [4].

For more on this exciting new combination, and how keeping it simple when sorting may lead to better transplantation outcomes, stay tuned to the Stem Cells Portal.

References

1. Fathman John W, Fernhoff Nathaniel B, Seita J, et al., Upregulation of CD11A on Hematopoietic Stem Cells Denotes the Loss of Long-Term Reconstitution Potential. Stem Cell Reports 2014;3:707-715.
2. Alborz K, M. SV, Erika V, et al., The CD11a and Endothelial Protein C Receptor Marker Combination Simplifies and Improves the Purification of Mouse Hematopoietic Stem Cells. STEM CELLS Translational Medicine 2018;7:468-476.
3. Kiel MJ, Yilmaz ÖH, Iwashita T, et al., SLAM Family Receptors Distinguish Hematopoietic Stem and Progenitor Cells and Reveal Endothelial Niches for Stem Cells. Cell 2005;121:1109-1121.
4. Fares I, Chagraoui J, Lehnertz B, et al., EPCR expression marks UM171-expanded CD34+ cord blood stem cells. Blood 2017;129:3344-3351.