PMID- 34047671 OWN - NLM STAT- MEDLINE DCOM- 20211130 LR - 20220204 IS - 2165-5987 (Electronic) IS - 2165-5979 (Print) IS - 2165-5979 (Linking) VI - 12 IP - 1 DP - 2021 Dec TI - Human umbilical cord-derived mesenchymal stem cells improve chronic pancreatitis in rats via the AKT-mTOR-S6K1 signaling pathway. PG - 1986-1996 LID - 10.1080/21655979.2021.1928441 [doi] AB - Chronic pancreatitis (CP) is a progressive inflammatory disease. In clinical treatment, many patients cannot get a timely diagnosis and effective treatment due to the lack of early diagnosis indicators. Mesenchymal stem cells have immunomodulatory and anti-inflammatory effects, and have broad application prospects in treating auto-immune diseases and inflammatory diseases. This study aimed to clarify the mechanisms of human umbilical cord mesenchymal stem cells (HUCMSCs) in the treatment of CP. The rats were randomly divided into four groups, with six rats in each group: control group, CP group, CP + HUCMSCs-treated group I, and CP + HUCMSCs-treated group II. We evaluated the levels of inflammatory factors, fibrosis and apoptosis markers, detected the protein expression levels of AKT-mTOR-S6K1 and assessed histological changes of the pancreas. The results showed that HUCMSCs not only inhibited the secretion of inflammatory cytokines and activation of pancreatic stellate cells but also suppressed the apoptosis of acinar cells. Further investigation revealed that HUCMSCs noticeably suppressed the AKT-mTOR-S6K1 pathway in the pancreatic tissue of DBTC-induced CP. In addition, the therapeutic effect of HUCMSCs injected into the inferior vena cava and left gastric artery in the CP model was also observed, thus providing the basis for the clinical application of intervention measures. FAU - Kong, Lijun AU - Kong L AD - Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Xu, Xiangxiang AU - Xu X AD - Ophthalmology Department, The Yiling Hospital of Yichang, Yichang, Hubei, China. FAU - Zhang, Hewei AU - Zhang H AD - Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Zhou, Yi AU - Zhou Y AD - Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Huang, Hongjian AU - Huang H AD - Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Chen, Bicheng AU - Chen B AD - Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Zhou, Zhenxu AU - Zhou Z AUID- ORCID: 0000-0002-9294-6332 AD - Department of Hernia and Abdominal Wall Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Bioengineered JT - Bioengineered JID - 101581063 RN - 0 (Cytokines) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases) RN - EC 2.7.11.1 (Rps6kb1 protein, rat) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Apoptosis/physiology MH - Cells, Cultured MH - Cytokines/metabolism MH - Fibrosis/metabolism MH - Human Umbilical Vein Endothelial Cells/*metabolism MH - Humans MH - Mesenchymal Stem Cells/*metabolism MH - Pancreas/cytology/metabolism MH - Pancreatic Stellate Cells/metabolism MH - Pancreatitis, Chronic/*metabolism MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Rats MH - Ribosomal Protein S6 Kinases/metabolism MH - Signal Transduction/physiology MH - TOR Serine-Threonine Kinases/*metabolism PMC - PMC8806739 OTO - NOTNLM OT - Chronic pancreatitis OT - fibrosis OT - inflammation OT - mesenchymal stem cell OT - pancreatic stellate cells EDAT- 2021/05/29 06:00 MHDA- 2021/12/01 06:00 PMCR- 2021/05/28 CRDT- 2021/05/28 12:11 PHST- 2021/05/28 12:11 [entrez] PHST- 2021/05/29 06:00 [pubmed] PHST- 2021/12/01 06:00 [medline] PHST- 2021/05/28 00:00 [pmc-release] AID - 1928441 [pii] AID - 10.1080/21655979.2021.1928441 [doi] PST - ppublish SO - Bioengineered. 2021 Dec;12(1):1986-1996. doi: 10.1080/21655979.2021.1928441.