Different mobilizers for different stem cells

London, UK -

While the human body does not have the regenerative capacity of a salamander, there are endogenous regenerative mechanisms that exist in the human.  For example, bone marrow progenitors are known to mobilize after situations of tissue injury, the idea being that they contribute to the healing process.  This is evident in stroke, where bone marrow CD34 cells increase in circulation, and patients having a higher increase actually end up undergoing more profound recovery.   

Conventionally, stem cell mobilizers have been used to alleviate the need for bone marrow puncture during stem cell collection.  It is a lot easier to give a donor a drug that makes the stem cells enter circulation, and then collect the stem cells from circulation.  The drug G-CSF is clinically approved for this purpose.  Experimental drugs in development for mobilizing stem cells include Orcrist Bio's HYC 750 candidate, parathyroid hormone, and antibodies to VCAM/VLA4.

While the majority of interest is in mobilizing hematopoietic stem cells, for use in hematopoietic stem cell transplants, there is an increasing interest in using stem cell mobilizers to mobilize mesenchymal stem cells or endothelial progenitor cells. 

A recent paper (Pitchford et al. Differential mobilization of subsets of progenitor cells from the bone marrow.  Cell Stem Cell 2009 Jan 9;4(1):62-72.) addressed the issue of selective mobilization. 

The investigators found:

a) VEGF pretreatment of mice before giving AMD3100 (CXCR-4 antagonist) increased the number of endothelial progenitor cells mobilized;

b) VEGF pretreatment decreased mobilization of hematopoietic stem cells after AMD3100 administration;

c) Only pretreatment with VEGF but not G-CSF would allow mobilization of mesenchymal stem cells.

These findings suggest it is possible to selectively mobilize specific stem cell compartments.  It will be interesting to see how this becomes applied clinically.  For example, why give exogenous stem cells for autoimmunity when you can simply mobilize your own ?  Would be nice.