Therapeutic effect of human clonal bone marrow-derived mesenchymal stem cells in severe acute pancreatitis
Severe acute pancreatitis (SAP), a common necroinflammatory disease initiated by the premature activation of digestive enzymes within the pancreatic acinar cells, is associated with significant morbidity and mortality. In this study, we investigated whether human bone marrow-derived clonal mesenchym...
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| Published in | Archives of pharmacal research Vol. 38; no. 5; pp. 742 - 751 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Seoul
Pharmaceutical Society of Korea
01.05.2015
대한약학회 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0253-6269 1976-3786 1976-3786 |
| DOI | 10.1007/s12272-014-0465-7 |
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| Abstract | Severe acute pancreatitis (SAP), a common necroinflammatory disease initiated by the premature activation of digestive enzymes within the pancreatic acinar cells, is associated with significant morbidity and mortality. In this study, we investigated whether human bone marrow-derived clonal mesenchymal stem cells (hcMSCs), isolated from human bone marrow aspirate according to our newly established isolation protocol, have potential therapeutic effects in SAP. SAP was induced by three intraperitoneal (i.p.) injections of cerulein (100 μg/kg) and sequential LPS (10 mg/kg) in Sprague-Dawley (SD) rats. hcMSCs (1 × 10
6
/head) were infused on 24 h after LPS injection via the tail vein. The rats were sacrificed 3 days after infusion of hcMSCs. We observed that infused hcMSCs reduced the levels of serum amylase and lipase. Infused hcMSCs ameliorated acinar cell necrosis, pancreatic edema, and inflammatory infiltration. Also, infused hcMSCs decreased the level of malondialdehyde, and increased the levels of glutathione peroxidase and superoxide dismutase. The number of TUNEL positive acinar cells was reduced after hcMSCs infusion. In addition, hcMSCs reduced the expression levels of pro-inflammation mediators and cytokines, and increased the expression of SOX9 in SAP. Taken together, hcMSCs could effectively relieve injury of pancreatitis as a promising therapeutics for SAP. |
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| AbstractList | Severe acute pancreatitis (SAP), a common necroinflammatory disease initiated by the premature activation of digestive enzymes within the pancreatic acinar cells, is associated with significant morbidity and mortality. In this study, we investigated whether human bone marrow-derived clonal mesenchymal stem cells (hcMSCs), isolated from human bone marrow aspirate according to our newly established isolation protocol, have potential therapeutic effects in SAP. SAP was induced by three intraperitoneal (i.p.) injections of cerulein (100 μg/kg) and sequential LPS (10 mg/kg) in Sprague-Dawley (SD) rats. hcMSCs (1 × 10(6)/head) were infused on 24 h after LPS injection via the tail vein. The rats were sacrificed 3 days after infusion of hcMSCs. We observed that infused hcMSCs reduced the levels of serum amylase and lipase. Infused hcMSCs ameliorated acinar cell necrosis, pancreatic edema, and inflammatory infiltration. Also, infused hcMSCs decreased the level of malondialdehyde, and increased the levels of glutathione peroxidase and superoxide dismutase. The number of TUNEL positive acinar cells was reduced after hcMSCs infusion. In addition, hcMSCs reduced the expression levels of pro-inflammation mediators and cytokines, and increased the expression of SOX9 in SAP. Taken together, hcMSCs could effectively relieve injury of pancreatitis as a promising therapeutics for SAP.Severe acute pancreatitis (SAP), a common necroinflammatory disease initiated by the premature activation of digestive enzymes within the pancreatic acinar cells, is associated with significant morbidity and mortality. In this study, we investigated whether human bone marrow-derived clonal mesenchymal stem cells (hcMSCs), isolated from human bone marrow aspirate according to our newly established isolation protocol, have potential therapeutic effects in SAP. SAP was induced by three intraperitoneal (i.p.) injections of cerulein (100 μg/kg) and sequential LPS (10 mg/kg) in Sprague-Dawley (SD) rats. hcMSCs (1 × 10(6)/head) were infused on 24 h after LPS injection via the tail vein. The rats were sacrificed 3 days after infusion of hcMSCs. We observed that infused hcMSCs reduced the levels of serum amylase and lipase. Infused hcMSCs ameliorated acinar cell necrosis, pancreatic edema, and inflammatory infiltration. Also, infused hcMSCs decreased the level of malondialdehyde, and increased the levels of glutathione peroxidase and superoxide dismutase. The number of TUNEL positive acinar cells was reduced after hcMSCs infusion. In addition, hcMSCs reduced the expression levels of pro-inflammation mediators and cytokines, and increased the expression of SOX9 in SAP. Taken together, hcMSCs could effectively relieve injury of pancreatitis as a promising therapeutics for SAP. Severe acute pancreatitis (SAP), a common necroinflammatory disease initiated by the premature activation of digestive enzymes within the pancreatic acinar cells, is associated with significant morbidity and mortality. In this study, we investigated whether human bone marrow-derived clonal mesenchymal stem cells (hcMSCs), isolated from human bone marrow aspirate according to our newly established isolation protocol, have potential therapeutic effects in SAP. SAP was induced by three intraperitoneal (i.p.) injections of cerulein (100 μg/kg) and sequential LPS (10 mg/kg) in Sprague-Dawley (SD) rats. hcMSCs (1 × 10⁶/head) were infused on 24 h after LPS injection via the tail vein. The rats were sacrificed 3 days after infusion of hcMSCs. We observed that infused hcMSCs reduced the levels of serum amylase and lipase. Infused hcMSCs ameliorated acinar cell necrosis, pancreatic edema, and inflammatory infiltration. Also, infused hcMSCs decreased the level of malondialdehyde, and increased the levels of glutathione peroxidase and superoxide dismutase. The number of TUNEL positive acinar cells was reduced after hcMSCs infusion. In addition, hcMSCs reduced the expression levels of pro-inflammation mediators and cytokines, and increased the expression of SOX9 in SAP. Taken together, hcMSCs could effectively relieve injury of pancreatitis as a promising therapeutics for SAP. Severe acute pancreatitis (SAP), a common necroinflammatory disease initiated by the premature activation of digestive enzymes within the pancreatic acinar cells, is associated with significant morbidity and mortality. In this study, we investigated whether human bone marrow-derived clonal mesenchymal stem cells (hcMSCs), isolated from human bone marrow aspirate according to our newly established isolation protocol, have potential therapeutic effects in SAP. SAP was induced by three intraperitoneal (i.p.) injections of cerulein (100 μg/kg) and sequential LPS (10 mg/kg) in Sprague-Dawley (SD) rats. hcMSCs (1 × 10(6)/head) were infused on 24 h after LPS injection via the tail vein. The rats were sacrificed 3 days after infusion of hcMSCs. We observed that infused hcMSCs reduced the levels of serum amylase and lipase. Infused hcMSCs ameliorated acinar cell necrosis, pancreatic edema, and inflammatory infiltration. Also, infused hcMSCs decreased the level of malondialdehyde, and increased the levels of glutathione peroxidase and superoxide dismutase. The number of TUNEL positive acinar cells was reduced after hcMSCs infusion. In addition, hcMSCs reduced the expression levels of pro-inflammation mediators and cytokines, and increased the expression of SOX9 in SAP. Taken together, hcMSCs could effectively relieve injury of pancreatitis as a promising therapeutics for SAP. Severe acute pancreatitis (SAP), a common necroinflammatory disease initiated by the premature activation of digestive enzymes within the pancreatic acinar cells, is associated with significant morbidity and mortality. In this study, we investigated whether human bone marrow-derived clonal mesenchymal stem cells (hcMSCs), isolated from human bone marrow aspirate according to our newly established isolation protocol, have potential therapeutic effects in SAP. SAP was induced by three intraperitoneal (i.p.) injections of cerulein (100 μg/kg) and sequential LPS (10 mg/kg) in Sprague-Dawley (SD) rats. hcMSCs (1 × 10 6 /head) were infused on 24 h after LPS injection via the tail vein. The rats were sacrificed 3 days after infusion of hcMSCs. We observed that infused hcMSCs reduced the levels of serum amylase and lipase. Infused hcMSCs ameliorated acinar cell necrosis, pancreatic edema, and inflammatory infiltration. Also, infused hcMSCs decreased the level of malondialdehyde, and increased the levels of glutathione peroxidase and superoxide dismutase. The number of TUNEL positive acinar cells was reduced after hcMSCs infusion. In addition, hcMSCs reduced the expression levels of pro-inflammation mediators and cytokines, and increased the expression of SOX9 in SAP. Taken together, hcMSCs could effectively relieve injury of pancreatitis as a promising therapeutics for SAP. Severe acute pancreatitis (SAP), a commonnecroinflammatory disease initiated by the premature activationof digestive enzymes within the pancreatic acinarcells, is associated with significant morbidity and mortality. In this study, we investigated whether human bone marrowderivedclonal mesenchymal stem cells (hcMSCs), isolatedfrom human bone marrow aspirate according to our newlyestablished isolation protocol, have potential therapeuticeffects in SAP. SAP was induced by three intraperitoneal(i.p.) injections of cerulein (100 lg/kg) and sequentialLPS (10 mg/kg) in Sprague-Dawley (SD) rats. hcMSCs(1 9 106/head) were infused on 24 h after LPS injection viathe tail vein. The rats were sacrificed 3 days after infusion ofhcMSCs. We observed that infused hcMSCs reduced thelevels of serum amylase and lipase. Infused hcMSCs amelioratedacinar cell necrosis, pancreatic edema, and inflammatoryinfiltration. Also, infused hcMSCs decreased thelevel of malondialdehyde, and increased the levels of glutathioneperoxidase and superoxide dismutase. The numberof TUNEL positive acinar cells was reduced after hcMSCsinfusion. In addition, hcMSCs reduced the expression levelsof pro-inflammation mediators and cytokines, and increasedthe expression of SOX9 in SAP. Taken together, hcMSCscould effectively relieve injury of pancreatitis as a promisingtherapeutics for SAP. KCI Citation Count: 24 |
| Author | Jung, Kyung Hee Yi, TacGhee Son, Mi Kwon Hong, Soon-Sun Song, Sun U. |
| Author_xml | – sequence: 1 givenname: Kyung Hee surname: Jung fullname: Jung, Kyung Hee organization: Department of Drug Development, Inha University School of Medicine, Translational Research Center and Inha Research Institute for Medical Sciences, Inha University School of Medicine – sequence: 2 givenname: TacGhee surname: Yi fullname: Yi, TacGhee organization: Department of Drug Development, Inha University School of Medicine, Translational Research Center and Inha Research Institute for Medical Sciences, Inha University School of Medicine – sequence: 3 givenname: Mi Kwon surname: Son fullname: Son, Mi Kwon organization: Department of Drug Development, Inha University School of Medicine, Translational Research Center and Inha Research Institute for Medical Sciences, Inha University School of Medicine – sequence: 4 givenname: Sun U. surname: Song fullname: Song, Sun U. email: sunuksong@inha.ac.kr organization: Translational Research Center and Inha Research Institute for Medical Sciences, Inha University School of Medicine – sequence: 5 givenname: Soon-Sun surname: Hong fullname: Hong, Soon-Sun email: hongs@inha.ac.kr organization: Department of Drug Development, Inha University School of Medicine, Translational Research Center and Inha Research Institute for Medical Sciences, Inha University School of Medicine |
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| Keywords | Severe acute pancreatitis (SAP) Amylase Lipase Human clonal bone marrow-derived mesenchymal stem cell (hcMSCs) |
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| Snippet | Severe acute pancreatitis (SAP), a common necroinflammatory disease initiated by the premature activation of digestive enzymes within the pancreatic acinar... Severe acute pancreatitis (SAP), a commonnecroinflammatory disease initiated by the premature activationof digestive enzymes within the pancreatic acinarcells,... |
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| SubjectTerms | acinar cells Animals blood serum bone marrow caudal vein cytokines digestive enzymes edema glutathione peroxidase Humans Inflammation Mediators - metabolism malondialdehyde Medicine Mesenchymal Stem Cell Transplantation - methods Mesenchymal Stromal Cells - metabolism morbidity mortality necrosis pancreatitis Pancreatitis - metabolism Pancreatitis - pathology Pancreatitis - therapy Pharmacology/Toxicology Pharmacy Rats Rats, Sprague-Dawley Research Article Severity of Illness Index stem cells superoxide dismutase therapeutics Treatment Outcome 약학 |
| Title | Therapeutic effect of human clonal bone marrow-derived mesenchymal stem cells in severe acute pancreatitis |
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