Effect of Hypoxia Preconditioned Adipose-Derived Mesenchymal Stem Cell Conditioned Medium on Cerulein-Induced Acute Pancreatitis in Mice

• Main Authors: Kamal Abdolmohammadi (Author), Tayebeh Mahmoudi (Author), Shahrzad Nojehdehi (Author), Lobat Tayebi (Author), Seyed Mahmoud Hashemi (Author), Farshid Noorbakhsh (Author), Alireza Abdollahi (Author), Masoud Soleimani (Author), Behrouz Nikbin (Author), Mohammad Hossein Nicknam (Author)
• Format: Book
• Published: Tabriz University of Medical Sciences, 2020-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2228-5881; 2251-7308; 10.34172/apb.2020.036
• Keywords: inflammation; acute pancreatitis; cerulein; mesenchymal stem cell; conditioned medium; preconditioning; Therapeutics. Pharmacology; RM1-950
• Source: Advanced Pharmaceutical Bulletin, Vol 10, Iss 2, Pp 297-306 (2020)

Purpose: Acute pancreatitis (AP) is an inflammatory disorder distinguished by tissue injury and inflammation of the pancreas. Using paracrine potential of mesenchymal stem cells (MSCs) provides a useful clinical approach in treating inflammatory diseases. We investigated the therapeutic effects of adipose-derived MSC conditioned medium (CM) and hypoxia preconditioned adipose-derived MSC conditioned medium (HCM) in cerulein-induced AP in mice. Methods: AP was induced in C57BL/6 mice by intraperitoneal injection of cerulein (75 μg/ kg/h × 7 times). One hour following the last injection of cerulein, mice were treated with intraperitoneal injection of CM and HCM (500 µL/mice/30 min × 3 times). Twelve hours following the treatment, serum levels of amylase and lipase were measured. In addition, pancreas pathological changes, immunohistochemical examinations for evaluation of IL-6 expression and pancreatic myeloperoxidase (MPO) enzyme activity were analyzed. Results: The in vitro results of the morphological, differentiation and immunophenotyping analyses confirmed that hypoxia preconditioned MSCs (HP-MSCs) conserve MSCs characteristics after preconditioning. However, HP-MSCs significantly expressed high mRNA level of hypoxia inducible factor 1-α and higher level of total protein. The in vivo findings of the current study showed that CM and HCM significantly reduced the amylase & lipase activity, the severity of pancreas tissue injury and the expression of IL-6 and MPO enzyme activity compared with the AP group. However, no significant difference between CM and HCM groups was demonstrated. Conclusion: Use of CM and HCM can attenuate cerulein-induced AP and decrease inflammation in the pancreas tissue in AP mice.