Fetal microchimerism in mouse caerulein-induced pancreatitis model

Document Type : Original Article


1 Laboratory for Stem Cell Research, Anatomy Department, Medical school, Shiraz University of Medical Sciences, Shiraz, Iran

2 Transplantation Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

3 Royan Institute for Stem Cell Biology and Technology, ACECR Department of Stem Cell and Developmental Biology, Cell Science Research Center, Tehran, Iran


Objective(s): Fetal microchimerism is the persistence of allogeneic cell population that transfer from the fetus to the mother. The aim of this study was to evaluate the presence of fetal microchimerism in the pancreas of the mouse with acute pancreatitis (AP).
Materials and Methods: In this experimental study, female wild-type mice were mated with male EGFP+. AP model was obtained by injection of caerulein two days after delivery. Sixty mice were divided into 3 groups:  the virgin pancreatitis-induced animals, pregnant pancreatitis-induced animals mated with transgenic EGFP mice, and pregnant sham animals. To prove pancreatitis induction, the blood amylase and lipase were assessed; and pancreas was removed from a subpopulation of each group for histopathological examinations after 6 hr. The remaining mice were kept for 3 weeks and histopathological exanimation, immunohistochemistry, and PCR were performed.
Results: EGFP+ cells were found in acini and around the blood vessels in the pancreas of pregnant pancreatitis-induced animals. They differentiated to acinar, adipocyte-like, and mesenchymal-like cells. PCR showed that 20% of the pregnant pancreatitis-induced animals were EGFP+. The histopathological study showed improvement in pancreatitis scores in the mice with history of pregnancy.
Conclusion: It seems that pregnancy has a beneficial impact on caerulein-induced pancreatitis and improves the pancreatitis score in mouse.


Main Subjects

1. Nelson JL. The otherness of self: microchimerism in health and disease. Trends Immunol 2012;33:421-427.
2. Gill RM, Lee TH, Utter GH, Reed WF, Wen L, Chafets D, et al.The TNF (− 308A) polymorphism is associated with microchimerism in transfused trauma patients. Blood 2008; 111: 3880-3883.
3. Boyon C, Collinet P, Boulanger L, Rubod C, Lucot JP, Vinatier D. Fetal microchimerism: benevolence or malevolence for the mother? Eur J Obstet Gynecol Reprod Biol 2011; 158:148-152.
4. Knippen MA. Microchimerism: Sharing Genes in Illness and in Health. ISRN Nurs 2011;2011: 893819.
5. Schnitzler M, Fisch P. A role for microchimerism in obesity and evolution? Med Hypotheses 2012; 78:528-532.
6. Fugazzola L, Cirello V, Beck-Peccoz P. Microchimerism and endocrine disorders. TJ Clin Endocrinol Metab 2012; 97:1452-1461.
7. Sunami R, Komuro M, Tagaya H, Hirata S. Migration of microchimeric fetal cells into maternal circulation before placenta formation. Chimerism 2010; 1: 66-68.
8. Dawe GS, Tan XW, Xiao ZC. Cell migration from baby to mother. Cell Adh Migr 2007; 1:19-27.
9. Klonisch T, Drouin R. Fetal–maternal exchange of multipotent stem/progenitor cells: microchimerism in diagnosis and disease. Trends Mol Med 2009; 15:510-518.
10. Khosrotehrani K, Johnson KL, Cha DH, Salomon RN, Bianchi DW. Transfer of fetal cells with multilineage potential to maternal tissue. LAMA 2004; 292:75-80.
11. Lee ES, Bou-Gharios G, Seppanen E, Khosrotehrani K, Fisk NM. Fetal stem cell microchimerism: natural-born healers or killers? Mol Hum Reprod 2010; 16:869-878.
12. Khosrotehrani K, Bianchi DW. Multi-lineage potential of fetal cells in maternal tissue: a legacy in reverse. J Cell Sci 2005; 118:1559-1563.
13. Pritchard S, Peter I, Johnson KL, Bianchi DW. The natural history of fetal cells in postpartum murine maternal lung and bone marrow: A two-stage phenomenon. Chimerism 2012; 3:59-64.
14. Fujiki Y, Tao K, Bianchi DW, Giel-Moloney M, Leiter AB, Johnson KL. Quantification of green fluorescent protein by in vivo imaging, PCR, and flow cytometry: comparison of transgenic strains and relevance for fetal cell microchimerism. Cytometry A  2008;  73:11-118.
15. Khosrotehrani K, Johnson KL, Lau J, Dupuy A, Cha DH, Bianchi DW. The influence of fetal loss on the presence of fetal cell microchimerism: a systematic review. Arthritis Rheu 2003; 48:3237-3241.
16. O’Donoghue K, Chan J, de la Fuente J, Kennea N, Sandison A, Anderson JR, et al. Microchimerism in female bone marrow and bone decades after fetal mesenchymal stem-cell trafficking in pregnancy. Lancet 2004; 364:179-182.
17. Wang Y, Iwatani H, Ito T, Horimoto N, Yamato M, Matsui I, et al.  Fetal cells in mother rats contribute to the remodeling of liver and kidney after injury. Biochem Biophys Res Commun 2004; 325:961-967.
18. Bayes-Genis A, Bellosillo B, de la Calle O, Salido M, Roura S, Ristol FS, et al. Identification of male cardiomyocytes of extracardiac origin in the hearts of women with male progeny: male fetal cell microchimerism of the heart. J Heart Lung Transplan 2005; 24:2179-2183.
19. Santos MA, O’Donoghue K, Wyatt-Ashmead J, Fisk NM. Fetal cells in the maternal appendix: a marker of inflammation or fetal tissue repair? Hum Reprod 2008; 23:2319-2325.
20. Zhang G, Zhao Y, Li XM, Kong J. Fetal cell microchimerism in the maternal mouse spinal cord. Neurosci Bull 2014; 30:81-89.
21. Nelson JL. Microchimerism and scleroderma. Curr Rheumatol Rep 1999; 1:15-21.
22. Lambert N. Microchimeric cells: guardians or actors of immunity in scleroderma? Rheumatology (Oxford) 2007; 46:382-383.
23. Ye Y, Berendine VZ, Hellmich C, Gillespie KM. Microchimerism: covert genetics? Int J Mol Epidemiol Gene 2010; 1:350-357.
24. VanZyl B, Gillespie KM. Microchimerism in type 1 diabetes. Curr Diab Rep 2009; 9:125-129.
25. Nguyen Huu S, Oster M, Avril MF, Boitier F, Mortier L, Richard MA, et al. Fetal microchimeric cells participate in tumour angiogenesis in melanomas occurring during pregnancy. Am J Pathol 2009; 174:630-637.
26. Johnson KL, Samura O, Nelson JL, McDonnell M d WM, Bianchi DW. Significant fetal cell microchimerism in a nontransfused woman with hepatitis C: Evidence of long‐term survival and expansion. Hepatology 2002; 36:1295-1297.
27. Sunami R, Komuro M, Yuminamochi T, Hoshi K, Hirata S. Fetal cell microchimerism develops through the migration of fetus-derived cells to the maternal organs early after implantation. J Reprod Immunol 2010; 84:117-123.
28. Tan XW, Liao H, Sun L, Okabe M, Xiao ZC, Dawe GS. Fetal microchimerism in the maternal mouse brain: a novel population of fetal progenitor or stem cells able to cross the blood–brain barrier? Stem Cells 2005; 23:1443-1452.
29. Carvalho KM, Morais TC, de Melo TS, de Castro Brito GA, de Andrade GM, Rao VS, et al.The natural flavonoid quercetin ameliorates cerulein-induced acute pancreatitis in mice. Biol Pharm Bull 2010; 33: 1534-1539.
30. Raraty MG, Murphy JA, Mcloughlin E, Smith D, Criddle D, Sutton R. Mechanisms of acinar cell injury in acute pancreatitis. Scand J Surg 2005; 94:89-96.
31. Lerch MM, Gorelick FS. Models of acute and chronic pancreatitis. Gastroenterology 2013; 144:1180-1193.
32. Lerch MM Gorelick FS. Models of acute and chronic pancreatitis. Gastroenterology, 2013; 144: 1180-1193.
33. Warzecha Z, Sendur P, Ceranowicz P, Dembiński M, Cieszkowski J, Kuśnierz-Cabala B, et al. Protective Effect of Pretreatment with Acenocoumarol in Cerulein-Induced Acute Pancreatitis. Int J Mol Sci 2016 ;17: E1709.
34. Welsch T, Endlich K, Giese T, Büchler MW, Schmidt J. Eps8 is increased in pancreatic cancer and required for dynamic actin-based cell protrusions and intercellular cytoskeletal organization. Cancer Let 2007; 255:205-218.
35. Nelson JL, Furst DE, Maloney S, Gooley T, Evans PC, Smith A, et al. Microchimerism and HLA-compatible relationships of pregnancy in scleroderma. The Lancet 1998; 351:559-562.
36. Johnson KL, Nelson JL, Furst DE, McSweeney PA, Roberts DJ, Zhen DK, et al. Fetal cell microchimerism in tissue from multiple sites in women with systemic sclerosis. Arthritis Rheum 2001; 44:1848-1854.
37. Ayatollahi M, Talaei-Khozani T, Razmkhah M. Growth suppression effect of human mesenchymal stem cells from bone marrow, adipose tissue, and Wharton’s jelly of umbilical cord on PBMCs. Iran J Basic Med Sci 2016; 19:145-1453.
38. Park CW, Kim KS, Bae S, Son HK, Myung PK, Hong HJ, et al. Cytokine secretion profiling of human mesenchymal stem cells by antibody array. Int J Stem Cells 2009; 2:59-68.
39. Nassar D, Khosrotehrani K, Aractingi S. Fetal microchimerism in skin wound healing. Chimerism 2012; 3:45-47.
40. Artlett CM, Rasheed M, Russo-Stieglitz KE, Sawaya HH, Jimenez SA. Influence of prior pregnancies on disease course and cause of death in systemic sclerosis. Ann Rheum Dis 2002; 61:346-350.
41. Florim GM, Caldas HC, de Melo JC, Baptista MA, Fernandes IM, Savoldi-Barbosa M, et al. Fetal microchimerism in kidney biopsies of lupus nephritis patients may be associated with a beneficial effect. Arthritis Res Ther 2015; 17:101.
42. da Silva Florim GM, Caldas HC, Pavarino EC, Bertollo EM, Fernandes IM, Abbud-Filho M. Variables associated to fetal microchimerism in systemic lupus erythematosus patients. Clin Rheumatol 2016; 35:107-111.
43. Bustos ML, Frías S, Ramos S, Estrada A, Arreola JL, Mendoza F, et al. Local and circulating microchimerism is associated with hypersensitivity pneumonitis. Am J Respir Crit Care Med 2007; 176:90-95.