Kamal Abdolmohammadi
1 
, Tayebeh Mahmoudi
2, Shahrzad Nojehdehi
3, Lobat Tayebi
4, Seyed Mahmoud Hashemi
5,6,7 , Farshid Noorbakhsh
1, Alireza Abdollahi
8,9, Masoud Soleimani
10 , Behrouz Nikbin
1,11, Mohammad Hossein Nicknam
1,11* 1 Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
2 Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran.
3 Stem Cell Technology Research Center, Tehran, Iran.
4 Marquette University School of Dentistry, Milwaukee, WI, 53233, USA.
5 Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
6 Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
7 Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
8 Department of Pathology, School of Medicine, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
9 Breast Disease Research Center (BDRC), Tehran University of Medical Sciences, Tehran, Iran.
10 Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
11 Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Abstract
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.