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The impact of CD34+ cell mobilization and cell functionality has not been extensively studied in the chronic myocardial ischemia (CMI) population. We examined the relationship between cell mobilization ability and in vitro CD34+ cell functionality. The migratory and clonogenic potential of CD34+ cells were compared between normal healthy donors and CMI subjects.
ACT34–CMI was a Phase 2 prospective, randomized, double–blind, placebo controlled study to evaluate the safety and efficacy of autologous–CD34+ cells administered via targeted intramyocardial delivery in refractory angina patients (N=167). Subjects were mobilized with subcutaneous injections of G–CSF (5 mcg/kg/day for 5 days). The mobilized apheresis product was collected on day 5 and the CD34+ cells were purified. Analyses of cell migration using a modified Boyden chamber and colony forming units (CFU–GM, BFU–E, CFU–GEMM, and CFU–E) were performed in a subset of CMI subject samples (N=24) to assess in vitro cell functionality of the selected CD34+ cells. Normal donor data for CFU (N=15) and cell migration (N=22) were used to evaluate in vitro functionality in CD34+ cells collected from normal donors vs. CMI subjects.
The ability to mobilize was not correlated with clonogenic potential of CD34+ cells from CMI subjects as measured by CFU–GM (p=0.624), BFU–E (p=0.682), CFU–GEMM (p=0.681) and CFU–E (p=0.452) or migratory potential (p=0.209). Mobilization ability did not appear to impact changes in angina frequency or change from baseline in total exercise time during the follow–up period. The CD34+ cells from the CMI subjects had a slightly increased migratory response as compared to normal donors (p=0.07). Normal donors tended to have greater number of total colonies than CMI subjects (p= 0.008).
Both good and poor mobilizers appear to respond similarly in terms of in vitro assessments of cell functionality and clinical improvements in angina frequency and change from baseline in total exercise time following intramyocardial delivery of Auto–CD34+ cells. When compared to normal healthy donors, CD34+ cells from CMI subjects appear to maintain a robust migratory response toward SDF–1α.
Poster Sessions, Expo North
Sunday, March 10, 2013, 3:45 p.m.–4:30 p.m.
Session Title: Cell Therapy and Angiogenesis
Abstract Category: 42. TCT@ACC–i2: Cell Therapy & Angiogenesis
Presentation Number: 2110–229
- 2013 American College of Cardiology Foundation