Researchers in Norman Iscove’s group published findings in this month’s edition of Cell Stem Cell identifying multipotent intermediate-term reconstituting hematopoietic stem cells (ITRC) that are distinguishable from long-term and short-term reconstituting hematopoietic stem cells (LTRC and STRC, respectively). These findings will allow investigators to distinguish between ITRC and LTRC, in order to more accurately study mechanisms that sustain long-term self-renewal in cells. Ultimately, these findings indicate that the first step in stem cell differentiation is a loss of mechanisms that stabilize self-renewing behaviour.

The team performed a detailed analysis of cell populations, including: comparisons of cell cycle status, response times to cytokines, ability to generate macroscopic spleen colonies, durability of grafts and erythroid engraftment potential to distinguish populations (CD49b^lo and CD49b^hi) of cells for more accurate analyses. A nearly complete segregation of LTRC to the CD49b^lo fraction (where they make up nearly 35% of cells) and a nearly complete segregation of ITRC into the CD49b^hi fraction was identified, allowing for a detailed gene expression analysis of the two populations that showed consistent differential expression between CD49b^lo and CD49b^hi cells. Therefore, Iscove and colleagues have managed to resolve, at a very high level, a fraction of cells containing solely LTRC rather than ITRC.

This study found that although the reconstitution patterns of ITRC and LTRC are distinguishable through tracking of erythroid or myeloid cells, they cannot be distinguished through measurement of donor leukocyte reconstitution alone. Therefore, previously published characterizations of critical hematopoietic stem cell (HSC) properties may not have differentiated between the LTRC and ITRC populations. To gain insight into the mechanisms of self-renewal it is critically important to isolate a pure population of LTRC in order to distinguish differences between long-, intermediate- and short-term reconstituting HSCs.

Intermediate term hematopoietic stem cells with extended but time-limited reconstitution potential. Benveniste P, Frelin C, Janmohamed S, Barbara M, Herrington R, Hyam D, Iscove NN. Cell Stem Cell. 2010 January 8. [Abstract]

The 2010 Stem Cell Engineering Conference will be held May 2-5, 2010 in Boston, MA. The meeting will be co-chaired by George Daley of the Children’s Hospital Harvard Medical School and the McEwen Centre’s Peter Zandstra. The conference is designed to bring together stem cell biologists and bioengineers in order to catalyze progress towards innovative solutions to problems in regenerative medicine.

The deadline for abstract submission is January 22, 2010. For more details, please visit www.aiche.org/StemCellEng.

Dr. Peter Zandstra was also named one of 2010’s people to watch by The Toronto Star on January 3. Dr. Zandstra, along with his U of T collaborator Dr. Milica Radisic, were recognized for their research in determining how stem cells can be integrated into the heart to repair damage. The article highlighted their recent publication identifying the stage of a heart cell that best integrates with engineered heart tissue, published in October’s Proceedings of the National Academy of Science USA, along with ongoing research into developing engineered tissue that mimics a patient’s heart tissue.