Angiogenesis requires endogenous stem cells

Nagoya, Japan -

Implantation of various stem cell populations into an ischemic muscle has been demonstrated to induce neovascularization both in animal studies, and in clinical trials.  Some people believe that the therapeutic angiogenesis may be occuring by differentiation of the stem cells injected into new endothelial cells, others believe that cytokines are produced by the injected cells and it is an interaction between the injected stem cells and the recipient muscle cells that causes therapeutic angiogenesis.  In a clinical trial it was demonstrated that patients with critical limb ischemia responding to exogenous stem cell implantation had an increased production of chemokines systemically, and a mobilization of endogenous bone marrow CD34 stem cells. 

Some people dont like the idea of having holes in their bones drilled to extract bone marrow for autologous stimulation of angiogenesis, therefore, there is research going on using adipose derived stem cells as an alternative to bone marrow.  Adipose stem cells have been demonstrated to possess therapeutic effects in pig infarct models by virtue of angiogenesis, as well, angiogenic potency of adipose derived stem cells can be guaged by CD9 expression.  Companies such as Cytori have patents on neat closed systems for purifying adipose mononuclear cells at the point of care.   Therefore, adipose stem cells appear, at least at face value to be a promising therapeutic modality for angiogenesis stimulation.

In a recent study (Kondo et al. Implantation of Adipose-Derived Regenerative Cells Enhances Ischemia-Induced Angiogenesis. Arterioscler Thromb Vasc Biol 2008 Oct 30), Adipose Regenerative Cells (sounds like Endometrial Regenerative Cells !?!) were demonstrated to induce neovascularization in a B6 mouse model of critical limb ischemia.  While this in itself may not be that exciting, since Keith March demonstrated adipose cells in a similar model being angiogenic by virtue of cytokine secretion 4 years ago, this study provided a brand new way of looking at adipose stem cells.

The study demonstrated that adipose stem cells injected intramuscularly into ischemic legs dependent on endogenous mobilization of bone marrow stem cells in order to mediate their angiogenic effect.  Furthermore, administration of systemic antibody to SDF-1 blocked mobilization and ability of the adipose stem cells to induce angiogenesis.

These data support the notion that therapeutic angiogenesis is a dynamic interaction between injected cell populations and endogenous stem cell reserves.