Role of bone marrow-derived cells in experimental chronic pancreatitis

Abstract

BMDCs contribute to the pancreatic stellate cell population, suggesting a role in pancreatic tissue repair. In the absence of preneoplastic lesions, BMDCs contribute at a very low level to the ductal epithelium of the chronically inflamed pancreas. The role of BMDCs in pancreatic carcinogenesis remains to be defined.

Bone marrow-derived pancreatic stellate cells in rats

“…Although these cell numbers are less than that in our regeneration model, the differences in injury protocol, animal species and quantification methodology for BM-derived PSCs used by these authors could account for the quantitative difference. Interestingly, in agreement with our observations, BM-derived acinar or islet cells could not be detected in the mouse model, and ductal cells were eGFP-positive only to a marginal extent [15]. These results suggest that BM cells do not contribute substantially to the replenishment of pancreatic epithelial cells after injury.…”

“…Our findings concerning the migration and differentiation of BM cells in the pancreas are supported by recent data of Marrache et al [15]. However, in contrast to our experimental model, which focused on tissue that has recovered from a relatively short-lived inflammatory reaction, these authors investigated the effects of severe chronic pancreatic damage induced by repeated injections of supramaximal doses of cerulein for 45 weeks into a mouse xenograft model using BM cells expressing eGFP.…”

“…Scar formation following a myocardial infarction has been shown to be associated with the appearance of BM-derived α-SMApositive myofibroblasts [14]. Using a mouse model of severe chronic pancreatic injury, Marrache et al [15] have shown that some stellate cells originated from the BM.…”

“…Reagents were purchased from the following sources: Histopaque 1083, monoclonal mouse antibodies directed against desmin, α-SMA, as well as an α-SMA-Cy3 antibody, Hoechst 33258, fuchsin, sodium nitrite, levamisole, naphtol-bis-phosphate, DBTC, oil red O and standard laboratory chemicals from Sigma (Deisenhofen, Germany); Iscove's modified Dulbecco's medium (IMDM), RPMI 1640 without phenol red, accutase from PAA (Cölbe, Germany); non-essential amino acids, penicillin, streptomycin, trypsin, superscript II reverse transcriptase, oligo (dT) [12][13][14][15][16][17][18] primer from Invitrogen (Karslruhe, Germany); Nycodenz from AXIS SHIELD PoC AS (Oslo, Norway); collagenase P from Roche (Mannheim, Germany); fetal calf serum (FCS) from Biochrom (Berlin, Germany); AlexaFluor 555 F(ab') 2 fragment goat anti-mouse or anti-rabbit from Molecular Probes (Eugene, OR, USA); monoclonal rat-specific anti-CD45-PE antibody from Acris (Hiddenhausen, Germany); anti-mouse IgG and monoclonal mouse APAAP complex from DAKO (Glostrup, Denmark). DNA isolation kit (innuPREP DNA Mini Kit) from Analytik Jena (Jena, Germany); TaqMan assays for real-time PCR from Applied Biosystems (Foster City, USA); BD FACS lysing solution, cell strainer from Becton Dickinson Labware (NJ, USA); RNeasy Mini RNA extraction kit, Taq Polymerase from Qiagen (Hilden, Germany); Immobilon-P (PVDF) membrane (Millipore, Bedford, MA, USA); rabbit anti-ERK (MAP kinase 42/44) antibody (Cell Signaling Technology, Beverly, MA, USA); ECL plus kit, horseradish peroxidase-labeled anti-rabbit or anti-mouse Ig antibody from Amersham (Freiburg, Germany); 12-mm diameter microscope cover glasses (Marienfeld, Lauda-Königshofen, Germany); BN/LEW hybrid were obtained from Charles River (Sulzfeld, Germany), transgenic LEW rats expressing eGFP under the control of the ubiquitin C promoter using a lentiviral vector construct, generated by Reichardt and co-workers [29], were propagated and generously provided by Manfred Lehmann (Institute of Biochemistry and Molecular Biology, University of Rostock, Rostock, Germany).…”

Chronic inflammation, the tumor microenvironment and carcinogenesis

“…It has been demonstrate that surgical tumor resection, in the recruitment of 5-6% of BMDCs into the tumor stroma, while early and advanced xenograft models of cancer result in the recruitment of ~12 and ~40% of BMDCs. 58,59 It is interesting to note that the proportion of bone marrow derived epithelial and stromal cells changes during tumor growth, and the contribution of BMDCs increases at later stages. This observation is especially relevant with evidence supporting the role of myofibroblasts in enhancing invasive properties of tumor epithelium.…”