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Enhancement of neovascularization with mobilized blood cells transplantaion: Supply of angioblasts and angiogenic cytokines
Author(s) -
Zhou Bin,
Liu Peng Xia,
Lan Hai Feng,
Fang Zhi Hong,
Han Zhi Bo,
Ren He,
Poon ManChiu,
Han Zhong Chao
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21290
Subject(s) - neovascularization , angiogenesis , matrigel , ischemia , transplantation , peripheral blood mononuclear cell , in vivo , blood vessel , perfusion , therapeutic angiogenesis , pathology , medicine , andrology , chemistry , biology , in vitro , biochemistry , microbiology and biotechnology
We have recently provided evidence that transplantation of G‐CSF mobilized peripheral blood mononuclear cells (M‐PBMNCs) improves limb ischemia in diabetic patients. This method represents a simple, safe, effective, and novel therapeutic approach for diabetic ischemia. Here we investigated the mechanisms by which mobilized blood cells transplantation improves limb ischemia. Unilateral hindlimb ischemia was surgically induced in streptozotocin‐induced diabetic nude mice, and they were intramuscularly injected 10 6 M‐PBMNCs, or human umbilical vein endothelial cells (HUVECs), PBS controls. We compared their blood‐flow restoration via laser Doppler perfusion image (LDPI), angiogenesis via histological determination of capillary density. Physiological and histological assessment revealed an acceleration of ischemia recovery and increase in capillary density with less apoptosis in M‐PBMNCs group, compared with those in HUVECs and PBS groups. In vivo noninvasive imaging and immunofluorescence revealed the survival, migration, proliferation, differentiation, and incorporation of M‐PBMNCs into foci of vessel networks. More angioblasts were from blood cells after mobilization, and they also produced a number of antiapoptotic and proagniogenic factors that promoted angiogenesis in vivo. M‐PBMNCs and its conditioned medium augmented the vessel formation in matrigel plugs in vivo. Thus, transplantation of M‐PBMNCs achieved therapeutic neovascularization via supply of abundant angioblasts and angiogenic factors. J. Cell. Biochem. 102: 183–195, 2007. © 2007 Wiley‐Liss, Inc.