The angiogenic properties of human adipose-derived stem cells (HASCs) are modulated by the High mobility group box protein 1 (HMGB1)

High-mobility group box 1 fragment suppresses adverse post-infarction remodeling by recruiting PDGFRα-positive bone marrow cells

“…tissue, such as peripheral artery disease and acute MI [24][25][26]. Indeed, in the present study, a significant increase in VEGF-A expression was found in the peri-infarction area of the HMGB1 group as compared with the control (Fig 2G).…”

“…The angiogenesis mechanism through VEGF-A by the recruited BM-MSCs should be further investigated. Because VEGF-A plays an important role in angiogenesis of HMGB1 as shown in our study and in previous reports [24][25][26], it would be useful to evaluate a model with blocked VEGF pathway to determine whether this increase has a causal role in documented angiogenesis. With respect to the mobilized BM-MSCs differentiation into the endothelial cells or pericytes, it is unclear whether GFP + /PDGFRα + and IL-B4 or NG2 are co-expressed because PDGFRα seems to be more highly expressed in the vessels, although other cells also seem to be slightly stained in red.…”

High Mobility Group Box-1 and Diabetes Mellitus Complications: State of the Art and Future Perspectives

“…Also, it has been demonstrated that patients with diabetic foot ulceration have higher serum levels of cytokines such as TNF-α, IL-6 and HMGB1, compared to diabetic patients without foot ulceration [88]. Despite these evidences, HMGB1 seems to be essential also in tissue repair after peripheral ischemia [89]. In fact, in diabetic mice with experimental model of limb ischemia, HMGB1 levels are decreased in ischemic tissues; furthermore, administration of HMGB1 improves neovascularization via a VEGF-dependent mechanism [45].…”

“…Interestingly, data by Xu and coworkers demonstrated that in mice with experimental limb ischemia, administration of chloroquine improves perfusion recovery and it induces HMGB1 release in sarcoplasm of muscle tissue and in serum [85]. It has been evaluated even the role of HMGB1 in cell therapy with human adipose-derived stem cells (HASCs) that are able to differentiate into EPCs with release of angiogenic and growth factors, given their stromal vascular fraction [89]. In particular, inhibition of HMGB1 in mice treated with human adipose-derived stem cells (HASCs) reduces VEGF levels and blood flow recovery, suggesting that HMGB1 positively influences HASCs treatment, promoting post-ischemic angiogenesis [89].…”

“…It has been evaluated even the role of HMGB1 in cell therapy with human adipose-derived stem cells (HASCs) that are able to differentiate into EPCs with release of angiogenic and growth factors, given their stromal vascular fraction [89]. In particular, inhibition of HMGB1 in mice treated with human adipose-derived stem cells (HASCs) reduces VEGF levels and blood flow recovery, suggesting that HMGB1 positively influences HASCs treatment, promoting post-ischemic angiogenesis [89]. However, in relation to the results of discussed evidences (Table 2), further research is needed to clarify the role of HMGB1 in PAD, and other clinical studies are needed to evaluate the role of this protein in patients with PAD subjected to revascularization of the lower limb in terms of outcome.…”