Hyperbaric Oxygen Therapy Enhanced Circulating Levels of Endothelial Progenitor Cells and Angiogenesis Biomarkers, Blood Flow, in Ischemic Areas in Patients with Peripheral Arterial Occlusive Disease

Abstract

Background: This study tested the hypothesis that hyperbaric oxygen (HBO) therapy enhanced the circulating levels of endothelial progenitor cells (EPCs), soluble angiogenesis factors, and blood flow in ischemic areas in patients with peripheral arterial occlusive disease (PAOD). Methods: In total, 57 consecutive patients with PAOD undergoing the HBO therapy (3 atmospheres (atm) for 2 h each time) were prospectively enrolled into the present study. Venous blood sampling was performed to assess the circulating levels of EPCs and soluble angiogenesis factors prior to and during five sessions of HBO therapy. Additionally, skin perfusion pressure (SPP), an indicator of blood flow in ischemic areas, was measured by moorVMS-PRES. Results: The results demonstrated that the circulating levels of EPCs (cluster of differentiation (CD)34+/CD133+/CD45dim, CD31+/CD133+/CD45dim, CD34+) and soluble angiogenesis factors—vascular endothelial growth factor/stromal cell-derived factor 1/hepatocyte growth factor/fibroblast growth factor (VEGF/SDF-1α/HGF/FGF) were significantly increased post-HBO therapy as compared to pre-HBO therapy (all p < 0.01). Additionally, Matrigel assay showed that the angiogenesis was significantly increased in post-HBO therapy as compared to prior to therapy (p < 0.001). Furthermore, SPP was significantly increased in the ischemic area (i.e., plantar foot and mean SPP of the ischemic foot) in post-HBO therapy as compared to pre-HBO therapy (all p < 0.01). Importantly, the HBO therapy did appear to result in complications, and all the patients were uneventfully discharged without amputation. Conclusions: HBO therapy augmented circulating levels of EPCs and angiogenesis factors, and improved the blood flow in the ischemic area.

Circulatory Rejuvenated EPCs Derived from PAOD Patients Treated by CD34+ Cells and Hyperbaric Oxygen Therapy Salvaged the Nude Mouse Limb against Critical Ischemia

“…Hyperbaric oxygen (HBO) therapy is a traditional therapy for patients with ischemic PAOD [ 23 ]. It is proposed that the underlying mechanism of HBO therapy that is predominantly involved in improving ischemic PAOD is the increase of vascular wall permeability and production of hypoxia-inducible factor (HIF)-1α and stromal cell-derived factor (SDF)-1α that enhance the angiogenesis, circulatory EPCs level and blood flow in the ischemic area [ 24 , 25 ]. Unsatisfactorily, the overall limb salvage and progression of the ischemic process have not been significantly decreased in patients receiving HBO therapy [ 26 ].…”

“…This may be due to the diffusion of oxygen into the ischemic organ that creates a hyperbaric environment being extremely limited [ 27 , 28 ] in severe PAOD patients. Interestingly, our recent study demonstrates that HBO increases the number and function of circulatory EPCs [ 25 ]. This finding highlights that HBO may play an accessory role in: (1) promoting the mobilization of EPCs from bone marrow to the circulation; (2) enhancing the capillary/microvascular permeability; (3) augmenting the intrinsic and extrinsic EPCs crossing the vessel wall and homing in on the ischemic area; and (4) acting as a contributor for repairing endothelial functions in the ischemic area via increasing oxygen diffusion into the ischemia, increasing the likelihood of successfully salvaging the limbs of CLI patients.…”

“…Based on the aforementioned issues [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ], we tested the hypothesis that treatment with EPCs derived from PAOD patients who received combined CD34 + cell and HBO therapy (defined as rejuvenated EPCs) would offer additional benefits than either one therapy alone for protecting limbs against the CLI procedure in nude mouse.…”

Combined Human Umbilical Cord-Derived Stem Cell and Hyperbaric Oxygen Therapy Effectively Preserved the Neurological Function and Brain Architecture in Rat After Acute Intracerebral Hemorrhage

“…The mechanisms for why MSCs and HBO therapy effectively protect the cells/tissues and organs from any ischemia-related damage always elicit high interest from scientists [35,36]. Currently, abundant data have shown that anti-in ammation, immunomodulation and tissue regeneration as well as cytokine/paracrine effects could be the main mechanisms for MSCs therapy on safeguarding the cells/tissues and organs far away from in ammatory and ischemic related damage [27,28,36].…”

Development and Evaluation of a Prototype Scratch Apparatus for Wound Assays Adjustable to Different Forces and Substrates

“…In addition to the mentioned cell types, endothelial cells are a favorable source to study migration. Many working groups used either human or bovine endothelial cells in scratch assays and other migration assays [47][48][49][50][51][52][53][54][55][56].…”