Delivery of human CD34+ cells and human peripheral non-selected blood mononuclear cells decreases neointima formation greater than culture-modified mononuclear cells in an immunodeficient rat carotid balloon injury model

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Background

There has been considerable interest in the use of cellular therapy to decrease neointima formation in the vascular system following balloon injury. We used a novel immunodeficient rat carotid injury model to determine if human cells of various phenotypes would decrease neointima formation in response to balloon injury.

Methods

Human buffy coat samples were obtained from healthy volunteers. Human peripheral non-selected blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation of heparinized blood. Human CD34+ cells were separated from buffy coat PBMCs immediately using automatic magnetic cell separation. Culture-modified mononuclear cells (CMMCs) were harvested after 6 to 8 days growth in vitro. Male Sprague-Dawley nude rats were anesthetized, the common carotid artery exposed. After

Results

Morphometric analysis of excised carotids showed a significant reduction to neointimal thickness in vessels from human CD34+– and human PBMC–treated animals 4 weeks after balloon injury compared with Human CMMC or saline-treated animals. Intima to media ratio was 0.39±0.08 vs 0.86±0.17 for saline treatment (P<.05). This suggests that local delivery of Human CD34+ cells and human PBMCs attenuated neointimal formation to a significantly greater extent than human CMMCs after mechanical injury.

Conclusion

CD34+ cells and PBMCs rather than CMMCs seem to have greater potential for use as a cellular therapy for vascular injury. The added advantage of same day processing of CD34+ cells and PBMCs before local delivery is also more favorable than the 6- to 8- day in vitro growth required for CMMCs.

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