Though animal studies using stem cells derived from the bone marrow have shown some improvement in cardiac function, but human trials have not been that successful.
To improve the results of cardiac human stem cell trials, senior study author, Dr. Wolfgang-Michael Franz from Ludwig-Maximilians University, advised, that modern approaches have to focus on the process of cardiac homing to improve the clinical outcome of stem cell therapies.
Scientists at Ludwig-Maximilians University find that the use of combined DPP-IV inhibition and G-CSF application as a new therapeutic concept for successful future stem cell trials.
They found that the stromal-cell-derived factor, type I (SDF-1) is the main chemical that guides stem cells to home in on damaged heart tissue.
Because SDF-1 is inactivated by CD26/dipeptidylpeptidase IV (DPP-IV), endogenous stem cell localization to the heart is not optimal.
The researchers used genetic or pharmacologic inhibitors of CD26/DPP-IV to slow degradation of SDF-1 in mice with surgically induced MI.
They also treated the mice with granulocyte colony stimulating factor (GCSF), a commonly used drug that mobilizes multiple stem cell populations from the bone marrow to the blood.
The researchers found that genetic or pharmacologic inhibition of CD26/DPP-IV combined with G-CSF treatment decreased DPP-IV and stabilized activated SDF-1 in the heart, thereby enhancing the recruitment of circulating blood forming precursor cells, or EPCs (endothelial progenitors) to this organ. Further, the combined treatment increased formation of new blood vessels and improved both survival and cardiac function after MI.
Scientists believe that the new findings may contribute essential new aspects for design of future stem cell trials, since the key issue of all therapeutic stem cell approaches emerges to be the process of cardiac homing.