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Far infra-red therapy promotes ischemia-induced angiogenesis in diabetic mice and restores high glucose-suppressed endothelial progenitor cell functions.

Huang PH, Chen JW, Lin CP, Chen YH, Wang CH, Leu HB, Lin SJ - Cardiovasc Diabetol (2012)

Bottom Line: Far infra-red (IFR) therapy was shown to exert beneficial effects in cardiovascular system, but effects of IFR on endothelial progenitor cell (EPC) and EPC-related vasculogenesis remain unclear.Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls, and significantly greater capillary density was seen in the IFR therapy group.In in-vitro studies, cultured EPCs treated with IFR radiation markedly augmented high glucose-impaired EPC functions, inhibited high glucose-induced EPC senescence and reduced H(2)O(2) production.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.

ABSTRACT

Background: Far infra-red (IFR) therapy was shown to exert beneficial effects in cardiovascular system, but effects of IFR on endothelial progenitor cell (EPC) and EPC-related vasculogenesis remain unclear. We hypothesized that IFR radiation can restore blood flow recovery in ischemic hindlimb in diabetic mice by enhancement of EPCs functions and homing process.

Materials and methods: Starting at 4 weeks after the onset of diabetes, unilateral hindlimb ischemia was induced in streptozotocin (STZ)-induced diabetic mice, which were divided into control and IFR therapy groups (n = 6 per group). The latter mice were placed in an IFR dry sauna at 34°C for 30 min once per day for 5 weeks.

Results: Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls, and significantly greater capillary density was seen in the IFR therapy group. Flow cytometry analysis showed impaired EPCs (Sca-1(+)/Flk-1(+)) mobilization after ischemia surgery in diabetic mice with or without IFR therapy (n = 6 per group). However, as compared to those in the control group, bone marrow-derived EPCs differentiated into endothelial cells defined as GFP(+)/CD31(+) double-positive cells were significantly increased in ischemic tissue around the vessels in diabetic mice that received IFR radiation. In in-vitro studies, cultured EPCs treated with IFR radiation markedly augmented high glucose-impaired EPC functions, inhibited high glucose-induced EPC senescence and reduced H(2)O(2) production. Nude mice received human EPCs treated with IFR in high glucose medium showed a significant improvement in blood flow recovery in ischemic limb compared to those without IFR therapy. IFR therapy promoted blood flow recovery and new vessel formation in STZ-induced diabetic mice.

Conclusions: Administration of IFR therapy promoted collateral flow recovery and new vessel formation in STZ-induced diabetic mice, and these beneficial effects may derive from enhancement of EPC functions and homing process.

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Morphology and characterization of human endothelial progenitor cells (EPCs) from peripheral blood. (A) Peripheral blood mononuclear cells (MNCs) were plated on a fibronectin-coated culture dish on the first day. (B) Four days after plating, adherent early EPCs with a spindle shape were shown. (C) Three weeks after plating, ECFCs with a cobblestone-like morphology were selected, reseeded, and grown to confluence. (D-I) ECFC characterization was performed by immunohistochemical staining. Most of the EPC expressed endothelial and hematopoietic stem cell markers, VE-cadherin, PECAM-1 (CD31), CD34, KDR, AC133, and eNOS, which are considered critical markers of EPCs. Cells were counterstained with 4',6-diamidino-2-phenylindole (DAPI) for the nuclei (blue).
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Figure 3: Morphology and characterization of human endothelial progenitor cells (EPCs) from peripheral blood. (A) Peripheral blood mononuclear cells (MNCs) were plated on a fibronectin-coated culture dish on the first day. (B) Four days after plating, adherent early EPCs with a spindle shape were shown. (C) Three weeks after plating, ECFCs with a cobblestone-like morphology were selected, reseeded, and grown to confluence. (D-I) ECFC characterization was performed by immunohistochemical staining. Most of the EPC expressed endothelial and hematopoietic stem cell markers, VE-cadherin, PECAM-1 (CD31), CD34, KDR, AC133, and eNOS, which are considered critical markers of EPCs. Cells were counterstained with 4',6-diamidino-2-phenylindole (DAPI) for the nuclei (blue).

Mentions: ECFCs were isolated from peripheral blood MNCs of healthy young adult volunteers as previously described [22]. The peripheral blood MNCs that initially seeded on fibronectin-coated wells were in round shape (Figure 3A). After the medium was changed on day 4, attached MNCs appeared to be elongated with a spindle shape (Figure 3B). ECFCs with a cobblestone-like morphology similar to mature endothelial cells were grown to confluence (Figure 3C). ECFCs characterization was performed by immunohistochemical staining, and most of the cells expressed mature endothelial markers, VE-cadherin, PECAM-1 (CD31), CD34, KDR, AC133 and eNOS (Figure 3), which are considered as critical markers of late EPCs.


Far infra-red therapy promotes ischemia-induced angiogenesis in diabetic mice and restores high glucose-suppressed endothelial progenitor cell functions.

Huang PH, Chen JW, Lin CP, Chen YH, Wang CH, Leu HB, Lin SJ - Cardiovasc Diabetol (2012)

Morphology and characterization of human endothelial progenitor cells (EPCs) from peripheral blood. (A) Peripheral blood mononuclear cells (MNCs) were plated on a fibronectin-coated culture dish on the first day. (B) Four days after plating, adherent early EPCs with a spindle shape were shown. (C) Three weeks after plating, ECFCs with a cobblestone-like morphology were selected, reseeded, and grown to confluence. (D-I) ECFC characterization was performed by immunohistochemical staining. Most of the EPC expressed endothelial and hematopoietic stem cell markers, VE-cadherin, PECAM-1 (CD31), CD34, KDR, AC133, and eNOS, which are considered critical markers of EPCs. Cells were counterstained with 4',6-diamidino-2-phenylindole (DAPI) for the nuclei (blue).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472269&req=5

Figure 3: Morphology and characterization of human endothelial progenitor cells (EPCs) from peripheral blood. (A) Peripheral blood mononuclear cells (MNCs) were plated on a fibronectin-coated culture dish on the first day. (B) Four days after plating, adherent early EPCs with a spindle shape were shown. (C) Three weeks after plating, ECFCs with a cobblestone-like morphology were selected, reseeded, and grown to confluence. (D-I) ECFC characterization was performed by immunohistochemical staining. Most of the EPC expressed endothelial and hematopoietic stem cell markers, VE-cadherin, PECAM-1 (CD31), CD34, KDR, AC133, and eNOS, which are considered critical markers of EPCs. Cells were counterstained with 4',6-diamidino-2-phenylindole (DAPI) for the nuclei (blue).
Mentions: ECFCs were isolated from peripheral blood MNCs of healthy young adult volunteers as previously described [22]. The peripheral blood MNCs that initially seeded on fibronectin-coated wells were in round shape (Figure 3A). After the medium was changed on day 4, attached MNCs appeared to be elongated with a spindle shape (Figure 3B). ECFCs with a cobblestone-like morphology similar to mature endothelial cells were grown to confluence (Figure 3C). ECFCs characterization was performed by immunohistochemical staining, and most of the cells expressed mature endothelial markers, VE-cadherin, PECAM-1 (CD31), CD34, KDR, AC133 and eNOS (Figure 3), which are considered as critical markers of late EPCs.

Bottom Line: Far infra-red (IFR) therapy was shown to exert beneficial effects in cardiovascular system, but effects of IFR on endothelial progenitor cell (EPC) and EPC-related vasculogenesis remain unclear.Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls, and significantly greater capillary density was seen in the IFR therapy group.In in-vitro studies, cultured EPCs treated with IFR radiation markedly augmented high glucose-impaired EPC functions, inhibited high glucose-induced EPC senescence and reduced H(2)O(2) production.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.

ABSTRACT

Background: Far infra-red (IFR) therapy was shown to exert beneficial effects in cardiovascular system, but effects of IFR on endothelial progenitor cell (EPC) and EPC-related vasculogenesis remain unclear. We hypothesized that IFR radiation can restore blood flow recovery in ischemic hindlimb in diabetic mice by enhancement of EPCs functions and homing process.

Materials and methods: Starting at 4 weeks after the onset of diabetes, unilateral hindlimb ischemia was induced in streptozotocin (STZ)-induced diabetic mice, which were divided into control and IFR therapy groups (n = 6 per group). The latter mice were placed in an IFR dry sauna at 34°C for 30 min once per day for 5 weeks.

Results: Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls, and significantly greater capillary density was seen in the IFR therapy group. Flow cytometry analysis showed impaired EPCs (Sca-1(+)/Flk-1(+)) mobilization after ischemia surgery in diabetic mice with or without IFR therapy (n = 6 per group). However, as compared to those in the control group, bone marrow-derived EPCs differentiated into endothelial cells defined as GFP(+)/CD31(+) double-positive cells were significantly increased in ischemic tissue around the vessels in diabetic mice that received IFR radiation. In in-vitro studies, cultured EPCs treated with IFR radiation markedly augmented high glucose-impaired EPC functions, inhibited high glucose-induced EPC senescence and reduced H(2)O(2) production. Nude mice received human EPCs treated with IFR in high glucose medium showed a significant improvement in blood flow recovery in ischemic limb compared to those without IFR therapy. IFR therapy promoted blood flow recovery and new vessel formation in STZ-induced diabetic mice.

Conclusions: Administration of IFR therapy promoted collateral flow recovery and new vessel formation in STZ-induced diabetic mice, and these beneficial effects may derive from enhancement of EPC functions and homing process.

Show MeSH
Related in: MedlinePlus