Therapeutic neovascularization by transplantation of mobilized peripheral blood mononuclear cells for limb ischemia

Shu Li; Bin Zhou; Zhong Chao Han

doi:10.1160/TH05-06-0442

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(02): 301-311
DOI: 10.1160/TH05-06-0442

Endothelium and Vascular Development

Schattauer GmbH

Therapeutic neovascularization by transplantation of mobilized peripheral blood mononuclear cells for limb ischemia

A comparison between CD34⁺ and CD34⁻ mononuclear cells

Authors

Shu Li^*

¹State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College; National Research Center for Cell Products Engineering, AmCellgene Co. Ltd, Tianjin, People’s Republic of China
Bin Zhou^*

¹State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College; National Research Center for Cell Products Engineering, AmCellgene Co. Ltd, Tianjin, People’s Republic of China
Zhong Chao Han

¹State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College; National Research Center for Cell Products Engineering, AmCellgene Co. Ltd, Tianjin, People’s Republic of China

Abstract

Summary

Autolougous transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized human peripheral blood mononuclear cells (PBMNCs) improves limb ischemia in patients with arteriosclerosis obliterans of lower extremities and with diabetic foot. However, the mechanism of action of PBMNCs remains elusive. Here, we studied comparatively the effects of the G-CSF-mobilized PBMNCs and CD34-depleted G-CSF-mobilized PBMNCs in an ischemia model of athymic nude mice. Fluorescence-labeled human PBMNCs [1×10⁶] were intramuscularly injected into the unilateral ischemic hindlimbs of mice. Laser Doppler imaging analysis revealed a significantly augmented blood perfusion at day 7, 14 and 28 after operation. The capillary density was also markedly increased and the rate of limb loss was significantly reduced in cell-transplanted groups when compared with those in PBS group. In comparison with G-CSF-mobilized PBMNCs, the therapeutic efficiency of G-CSF-mobilized PBMNCs deprived of CD34⁺ cells was impaired. Transplanted cells were found to accumulate around arterioles and scatter in capillary networks. Incorporation of transplanted cells into new capillaries was observed in the G-CSF-mobilized PBMNCs group, but was not detected in the group deprived of CD34⁺ cells. There was an elevated expression of VEGF in ischemic tissue. Colocalization of VEGF and transplanted mononuclear cells within adductor tissue was demonstrated. These findings indicate that G-CSF-mobilized PBMNCs promote vascular growth not only by incorporating into vessel walls but also by supplying angiogenic factors. The depletion of CD34⁺ cells attenuated the therapeutic efficiency of G-CSF-mobilized PBMNCs in response to ischemia-induced neovascularization.

Keywords

G-CSF-mobilized PBMNCs - ischemia - neovascularization - CD34 - VEGF

Full Text

References

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