Abstract 14569: Mesenchymal Stromal Cells Obtained From Patients With Critical Limb Ischemia Are Not Dysfunctional Compared to Healthy Controls
Introduction: Critical Limb Ischemia (CLI) is an advanced form of peripheral arterial disease, for which surgical treatment options are often limited. Cell therapy aimed at neovascularization using bone-marrow derived cells (BMCs) has shown promising results, but the effect of autologous BMCs may be limited in patients due to disease-mediated progenitor cell dysfunction. We hypothesize that after ex vivo expansion, BM derived Mesenchymal Stromal Cells (MSCs) from CLI patients show no functional impairments.
Methods: BM-MSCs were obtained from 12 CLI patients included in a cell-therapy trial and 12 controls undergoing elective orthopedic surgery. Gene expression profiling using Illumina Microarrays was performed on 6 donors from each group. MSC function in all donors was quantified on chondrogenic, adipogenic and osteogenic differentiation; senescence by ß-galactosidase activity; and migration towards PDGF-BB by modified Boyden chamber assay. Ability to promote neovascularization of MSCs from 10 donors in each group was investigated in a murine model of hind-limb ischemia (3 mice/donor and 21 vehicle controls).
Results: Gene expression profiling identified no significantly differentially expressed genes. High within-group variability was found in genes associated with immune responses and ‘stemness’. No differences were observed in adipogenic or osteogenic capacity of MSCs. CLI-MSCs showed a reduced ability towards chondrogenic differentiation and increased senescence compared to control MSCs. These differences disappeared after a correction for donor age. We observed a dose-dependent migration towards PDGF-BB, with no differences in EC50 values between CLI-MSC and controls. In the hind-limb ischemia model, recovery of perfusion after 10 days was 71 ± 24% (SD) in MSC treated mice and 44 ± 11% percent in vehicle controls (p<1x10-6). CLI-MSC and control-MSC were (bio-)equivalent (95% CI 0.85-1.15).
Conclusion: MSCs obtained from CLI patients show no functional impairment compared to MSCs from healthy donors. This suggests that autologous MSCs are suitable for cell therapies intended to promote neovascularization in CLI patients.
- Peripheral arterial disease
- Stem/progenitor cells
- Stem cell therapy
- Regenerative medicine stem cells
- Vascular disease
- © 2013 by American Heart Association, Inc.