• BMB Reports
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• v.55 no.7
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• pp.336-341
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• 2022

Narrowing of arteries supplying blood to the limbs provokes critical hindlimb ischemia (CLI). Although CLI results in irreversible sequelae, such as amputation, few therapeutic options induce the formation of new functional blood vessels. Based on the proangiogenic potentials of stem cells, in this study, it was examined whether a combination of dental pulp stem cells (DPSCs) and human umbilical vein endothelial cells (HUVECs) could result in enhanced therapeutic effects of stem cells for CLI compared with those of DPSCs or HUVECs alone. The DPSCs+ HUVECs combination therapy resulted in significantly higher blood flow and lower ischemia damage than DPSCs or HUVECs alone. The improved therapeutic effects in the DPSCs+ HUVECs group were accompanied by a significantly higher number of microvessels in the ischemic tissue than in the other groups. In vitro proliferation and tube formation assay showed that VEGF in the conditioned media of DPSCs induced proliferation and vessel-like tube formation of HUVECs. Altogether, our results demonstrated that the combination of DPSCs and HUVECs had significantly better therapeutic effects on CLI via VEGF-mediated crosstalk. This combinational strategy could be used to develop novel clinical protocols for CLI proangiogenic regenerative treatments.

• Biomolecules & Therapeutics
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• v.28 no.3
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• pp.240-249
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• 2020

Despite the therapeutic effect of mesenchymal stem cells (MSCs) in ischemic diseases, pathophysiological conditions, including hypoxia, limited nutrient availability, and oxidative stress restrict their potential. To address this issue, we investigated the effect of melatonin on the bioactivities of MSCs. Treatment of MSCs with melatonin increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α). Melatonin treatment enhanced mitochondrial oxidative phosphorylation in MSCs in a PGC-1α-dependent manner. Melatonin-mediated PGC-1α expression enhanced the proliferative potential of MSCs through regulation of cell cycle-associated protein activity. In addition, melatonin promoted the angiogenic ability of MSCs, including migration and invasion abilities and secretion of angiogenic cytokines by increasing PGC-1α expression. In a murine hindlimb ischemia model, the survival of transplanted melatonin-treated MSCs was significantly increased in the ischemic tissues, resulting in improvement of functional recovery, such as blood perfusion, limb salvage, neovascularization, and protection against necrosis and fibrosis. These findings indicate that the therapeutic effect of melatonin-treated MSCs in ischemic diseases is mediated via regulation of PGC-1α level. This study suggests that melatonin-induced PGC-1α might serve as a novel target for MSC-based therapy of ischemic diseases, and melatonin-treated MSCs could be used as an effective cell-based therapeutic option for patients with ischemic diseases.

• Archives of Reconstructive Microsurgery
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• v.14 no.2
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• pp.85-94
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• 2005

Purpose: This study was to evaluate the effect of ${\alpha}-lipoic$ acid, a potent free radical scavenger, on the expression of active form of extracellular signal-regulated kinase (pERK1/2) proteins from hindlimb muscles of rats following ischemia-reperfusion injury. Material and methods: 64 health, $280{\sim}350\;g$ weighted Sprague-Dawley male rats were used. In order to make a muscle flap, the gastrocnemius (GC) and soleus (SOL) muscles were dissected and elevated. The popliteal artery was occluded for 4hours and reperfused for 10 minutes, 30 minutes, 1 hour, 2 hours and 4 hours, respectively. Results: The ischemia by occlusion of the popliteal artery itself caused a minimal change in expression of phosphorylated form of proteins observed in hindlimb muscle. In contrast, after 4 hours of ischemia, immunoreactivity for pERK1/2 in the GC muscle showed dual peaks at 10 minutes and 4 hours after reperfusion. In ${\alpha}-lipoic$ acid treated group, the expression of pERK1/2 was increased significantly compared to I/R-only group. Conclusion: These results suggest that ${\alpha}-lipoic$ acid may protect I/R injury of the skeletal muscle through free radical scavening and activation of intracellular pERK1/2 expression.

• Journal of Korean Academy of Nursing
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• v.34 no.1
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• pp.150-159
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• 2004

Purpose: The purpose of this study was to determine the effect of DHEA on hindlimb muscles(soleus, plantaris and gastrocnemius) in a focal brain ischemia model rat. Method: Twenty-seven male Sprague-Dawley rats were randomly divided into three groups: CINS(cerebral ischemia + normal saline), CIDH(cerebral ischemia + DHEA), or SHNS(sham + normal saline). Both the CINS and CIDH groups underwent a transient right middle cerebral artery occlusion operation. In the SHNS group, a sham operation was done. 0.34mmol/kg DHEA was administered daily by an intraperitoneal injection for 7days. Results: The muscle weight, muscle fiber cross-sectional area of the Type I muscle fiber of soleus and Type II muscle fiber of plantaris and gastrocnemius, myofibrillar protein content of gastrocnemius, and muscle strength in the CINS group decreased compared with the SHNS group. The muscle weight, muscle fiber cross-sectional area of the Type II muscle fiber of plantaris and gastrocnemius, myofibrillar protein content of soleus, and muscle strength in the CIDH group increased compared with the CINS group. Conclusion: It was identified that muscle atrophy could be induced during 7 days after a cerebral infarction, and DHEA administration during the early stages of a cerebral infarction might attenuate muscle atrophy.

• Journal of Korean Academy of Nursing
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• v.36 no.7
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• pp.1232-1241
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• 2006

Purpose: The purpose of this study was to examine the effects of cerebral ischemia on Type I(soleus) and Type II(plantaris, gastrocnemius) muscles, and to determine the effects of isometric contraction training by electro- stimulation on Type I and II muscles in cerebral ischemia model rats. Method: Twenty-five male Sprague-Dawley rats were randomly divided into four groups: ST(stroke), STES(stroke+electrostimulation), SH(sham) and SHES (sham+electrostimulation). The ST and STES groups received a transient right middle cerebral artery occlusion operation. The SH and SHES groups received a sham operation. The STES and SHES groups had daily isometric contraction training by electrostimulation(100Hz, 45mA, 7.5V) on hindlimb muscles for 7days. Result: Plantaris and gastrocenmius muscle weight, myofibrillar protein contents of soleus and gastrocnemius, and the muscle fiber cross-sectional area of gastrocnemius in the ST group significantly decreased compared with the SH group. Soleus, plantaris, gastrocnemius muscle weight, myofibrillar protein contents of soleus and gastrocnemius, and the Type I muscle fiber cross-sectional area of soleus and the Type II muscle fiber cross-sectional area of gastrocnemius in the STES group significantly increased compared with the 57 group. Conclusion: Hindlimb muscle atrophy occurs after acute stroke and isometric contraction training by electrostimulation during early stages of a stroke attenuates muscle atrophy of Type I and Type II muscles.

• Biomolecules & Therapeutics
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• v.29 no.4
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• pp.454-454
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• 2021

• BMB Reports
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• v.50 no.10
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• pp.504-509
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• 2017

Ischemia is a serious disease, characterized by an inadequate blood supply to an organ or part of the body. In the present study, we evaluated the effects of the anti-microbial peptide SR-0379 on the stem cell-mediated therapy of ischemic diseases. The migratory and tube-forming abilities of human endothelial progenitor cells (EPCs) were enhanced by treatment with SR-0379 in vitro. Intramuscular administration of SR-0379 into a murine ischemic hindlimb significantly enhanced blood perfusion, decreased tissue necrosis, and increased the number of blood vessels in the ischemic muscle. Moreover, co-administration of SR-0379 with EPCs stimulated blood perfusion in an ischemic hindlimb more than intramuscular injection with either SR-0379 or EPCs alone. This enhanced blood perfusion was accompanied by a significant increase in the number of CD31- and ${\alpha}$-SMA-positive blood vessels in ischemic hindlimb. These results suggest that SR-0379 is a potential drug candidate for potentiating EPC-mediated therapy of ischemic diseases.

• The Journal of Korean Physical Therapy
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• v.13 no.1
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• pp.41-48
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• 2001

The purpose of this study was to investigate the effect of cold application on ischemia-reperfusion injury to quadriceps fomoris muscle of the hindlimbs of the rats. Nine weeks old male Sprague-Dawley white rats were divided into three groups : 1) control(only ischemia-reperfusion), 2) cold application before reperfusion(PreCold), 3) cold application after reperfusion(PostCold). All groups were 30 minute, 1 hour, 3 hours reperfusion after 2 hours ischemia with clamping abdominal artery, and investigate superoxide dismutase(SOD) immunohistochemical reaction for quadriceps femoris muscle of right hindlimb. SOD immunohistochemical reaction of experimental groups were more than the control group. Especially, SOD immunohistochemical reaction of PreCold were less than the PostCold.

• 대한핵의학회:학술대회논문집
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• 2006.05a
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• pp.51-52
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• 2006

• Journal of Korean Biological Nursing Science
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• v.4 no.1
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• pp.51-69
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• 2002

The purpose of this study was to identify the effect of cerebral ischemia on affected(Lt) and unaffected(Rt) side of soleus, plantaris and gastrocnemius muscle mass and determine the effect of exercise on affected and unaffected side on soleus, plantaris and gastrocnemius muscle mass during acute stage of stroke. Sixteen male Sprague-Dawley rate with 200-270g body weight were randomly divided into three groups: control, stroke, and exercise after stroke(St+Ex) group. The control group received sham operation and the stroke group and St+Ex group received transient right MCA(middle cerebral artery) occlusion operation. The St+Ex groups ran on a treadmill for 20min/day at 10m/min and $10^{\circ}$ grade for 6days. During the experimental period body weight and diet intake was measured every morning. On the 7th day after operation, muscles were dissected from both affected and unaffected side of hindlimb. Cerebral infarction of stroke and St+Ex groups were identified by staining with TCC for 30 minutes. The data were analyzed by Kruskal-Wallis test and Mann-Whitney U test using the SPSSWIN 9.0 program. Significance was accepted at the level of p<0.05. The results were summarized follows : 1) There were no significant difference of the body weight on the first day of experiment among 3 groups. Whereas on the 7th day, the body weight of both stroke group and St+Ex group were significantly smaller than that of control group. Body weight of St+Ex group on the 7th day tended to be larger than that of stroke group. 2) Total diet intake of both stroke group and St+Ex group were also significantly smaller than that of control group. While total amount of diet intake in St+Ex group tended to be larger than that of stroke group. 3) The weight of gastrocnemius muscle of affected side in stroke group significantly decreased compared to that of control group and the weight of soleus and plantaris muscle of affected side in stroke group tended to decrease compared to that of control group. 4) The weight of plantaris muscle of unaffected side in stroke group significantly decreased compared to that of control group and the weight of soleus and gastrocnemius muscle of unaffected side in stroke group tended to decrease compared to those of control group. 5) The weight of gastrocnemius muscle of affected side in stroke group significantly decreased compared to that of unaffected side and there was no significant difference of the weight of soleus and plantaris muscle in stroke group between affected side and unaffected side. 6) The weight of soleus, plantaris and gastrocnemius muscle of both affected side and unaffected side in St+Ex group had a tendency of increase compared to those of stroke group. The relative weight of soleus and gastrocnemius muscle of affected side and soleus muscle of unaffected side in St+Ex group had a tendency to increase compared to those of stroke group. Based on these results, exercise during acute stage of stroke might attenuate muscle atrophy of both affected and unaffected side of hindlimb muscles.