Immunologic Network and Response to Intramyocardial CD34+ Stem Cell Therapy in Patients With Dilated Cardiomyopathy

• The aim of this study was to identify immune and nonimmune factors associated with response to intramyocardial CD34+ stem cell–based therapy in patients with dilated cardiomyopathy (DCM).
• Patients with DCM demonstrate changes not only in inflammatory markers but also in growth factors, stem cell factors, and metabolic factors.
• Responders to CD34+-based stem cell therapy appear to have a different baseline biomarker profile than nonresponders.
• Factors positively associated with both clinical response and stem cell retention included GCSF, SDF-1, LIF, MCP-1, and MCP-3. Factors negatively associated with both clinical response and stem cell retention included IL-12p70, FASL, ICAM-1, and GGT.

BackgroundAlthough stem cell therapy (SCT) is emerging as a potential treatment for patients with dilated cardiomyopathy (DCM), clinical response remains variable. Our objective was to determine whether baseline differences in circulating immunologic and nonimmunologic biomarkers may help to identify patients more likely to respond to intramyocardial injection of CD34+-based SCT.Methods and ResultsWe enrolled from January 3, 2011 to March 5, 2012 37 patients with longstanding DCM (left ventricular ejection fraction [LVEF] <40%, New York Heart Association functional class III) who underwent peripheral CD34+ stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) and collection by means of apheresis. CD34+ cells were labeled with 99mTc-hexamethylpropyleneamine oxime to allow assessment of stem cell retention at 18 hours. Response to SCT was predefined as an increase in LVEF of ≥5% at 3 months. The majority (84%) of patients were male with an overall mean LVEF of 27 ± 7% and a median N-terminal pro–B-type natriuretic peptide (NT-proBNP) level of 2,774 pg/mL. Nineteen patients (51%) were responders to SCT. There was no significant difference between responders and nonresponders regarding to age, sex, baseline LVEF, NT-proBNP levels, or 6-minute walking distance. With the use of a partial least squares (PLS) predictive model, we identified 9 baseline factors that were associated with both stem cell response and stem cell retention (mechanistic validation). Among the baseline factors positively associated with both clinical response and stem cell retention were G-CSF, SDF-1, LIF, MCP-1, and MCP-3. Among baseline factors negatively associated with both clinical response and retention were IL-12p70, FASL, ICAM-1, and GGT. A decrease in G-CSF at 3-month follow-up was also observed in responders compared with nonresponders (P = .02).ConclusionsIf further validated, baseline immunologic and nonimmunologic biomarkers may help to identify patients with DCM who are more likely to respond to CD34+-based SCT.