Objective-Therapeutic angiogenesis using autologous stem/progenitor cells represents a novel strategy for severe ischemic diseases. Recent reports indicated that adipose tissues could supply adipose-derived regenerative cells (ADRCs). Accordingly, we examined whether implantation of ADRCs would augment ischemia-induced angiogenesis. Method and Results-Adipose tissue was obtained from C57BL/6J mice, and ADRCs were isolated using standard methods. ADRCs expressed stromal cell-derived factor 1 (SDF-1) mRNA and proteins. Hind limb ischemia was induced and culture-expanded ADRCs, PBS, or mature adipocytes (MAs) as control cells were injected into the ischemic muscles. At 3 weeks, the ADRC group had a greater laser Doppler blood perfusion index and a higher capillary density compared to the controls. Implantation of ADRCs increased circulating endothelial progenitor cells (EPCs). SDF-1 mRNA abundance at ischemic tissues and serum SDF-1 levels were greater in the ADRC group than in the control group. Finally, intraperitoneal injection of an anti-SDF-1 neutralizing antibody reduced the number of circulating EPCs and therapeutic efficacies of ADRCs. hen tissue is exposed to severe ischemia, new blood vessels develop into the ischemic foci to prevent tissue necrosis. Because circulating endothelial progenitor cells (EPCs) have been shown to participate in postnatal neovascularization after mobilization from the bone marrow (BM), 1,2 we have performed basic and clinical studies related to therapeutic angiogenesis using EPCs or BM cells. [3][4][5] We have performed therapeutic angiogenesis using autologous BM mononuclear cell (BM-MNCs) implantation into the ischemic muscles in patients with critical limb ischemia (TACT). 6 -8 Although the safety and efficiency of the TACT protocol have been established, we recently reported that patients with very severe peripheral artery occlusive disease had poor responses to the TACT procedure. 7 Moreover, recent data indicated that patients with severe obstructive vascular disease or multiple coronary risk factors had diminished functions of EPCs and poor responses to angiogenic cell therapy. 9 -12 Thus, alternative source of stem/progenitor cells for therapeutic angiogenesis has been searched extensively. Conclusions-AdiposeRecently, several investigators have reported that adipose tissues contain multipotent mesenchymal stem cells termed adipose-derived regenerative cells (ADRCs), which have an ability to regenerate damaged tissues. [13][14][15] However, little is known as to how implantation of ADRCs would induce angiogenesis in ischemic tissues. It has been known that ADRCs secrete multiple angiogenic growth factors such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). 13,14 Such growth factors would mobilize EPCs from the BM into peripheral blood (PB) and finally to ischemic tissues. However, there is limited evidence regarding the effects of in vivo implantation of ADRCs on EPC kinetics during ischemia-induced angiogenesis.Accordingly, we examined ...

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atients with end-stage renal disease (ESRD) on hemodialysis (HD) are at high risk of death from ischemic heart disease. 1-3 Furthermore, percutaneous coronary intervention (PCI) in such patients is sometimes difficult because they have more complex lesions, including massive calcification of coronary lesions and/or multivessel disease than non-HD patients. 4 Published reports have indicated that using new devices such as stents or debulking devices is associated with better outcomes after PCI in HD patients. 5,6 However, the restenosis rate in the follow-up period is higher in HD patients than in non-HD patients, although the initial success rate of PCI is similarly high in both groups. 7-10 Therefore, higher rates of restenosis remain a clinical limitation of cardiac interventions in HD patients.Recently it was reported that sirolimus-eluting stents (SES) significantly reduce the risk of restenosis after PCI in many cases, [11][12][13][14][15] and the remarkable safety and efficacy of SES has been documented not only by angiography but by intravascular ultrasound (IVUS) as well. 16,17 Moreover, even in patients with high-risk factors for coronary restenosis, including diabetes, small diameter vessels, chronic total occlusion and so on, clinical improvement has been observed. [18][19][20][21] Accordingly, in the present study we aimed to determine the efficacy of SES in patients on maintenance HD. Methods Study PopulationFrom August 2004, SES have been available in our institution, so between August 2004 and July 2005 we attempted to implant SES for all patients who needed PCI if they had no contraindications, such as acute coronary syndrome, intolerance of both of aspirin and ticlopidine, planned surgery and so on. In total, 225 consecutive Japanese patients with 322 lesions treated with SES (Cypher™) for native coronary lesions during that period were designated as the SES group and 256 patients with 307 lesions treated with bare metal stents (BMS) in the preceding 1 year were the BMS group. Of these, 166 patients with 216 lesions (88 patients with 121 lesions in the SES group and 78 patients with 95 lesions in the BMS group) received maintenance HD 3 times a week. In advance, we excluded patients who were diagnosed with acute myocardial infarction (MI), underwent bypass grafting, had a contraindication for the use of aspirin and/or ticlopidine, or were >85 years of age.Lesions were suitable for PCI if they were de novo

These results suggest that even in young men, plasma adiponectin levels can predict endothelial dysfunction before any overt vascular disease has occurred. HMW adiponectin may be more useful as a marker of endothelial dysfunction than total adiponectin.

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