Crosstalk Between Activated Myofibroblasts and β Cells in Injured Mouse Pancreas.
OBJECTIVE
In injury conditions, myofibroblasts are induced to lay down matrix proteins and support the repair process. In this study, we investigated the role of myofibroblasts, particularly stellate cells, in the growth and regeneration of pancreatic β cells.


METHODS
We used both in vitro and in vivo approaches to address whether stellate cells may promote the growth of β cells.


RESULTS
Our experiments demonstrated that activated stellate cells support the proliferation of β cells in vitro. In vivo, mesenchymals surrounding the pancreatic islets are activated (induced to proliferate) in the islet regeneration model of Pten null mice. These mesenchymals display markers of pancreatic stellate cells, such as desmin and to a lesser extent, smooth muscle actin α. We have shown previously that targeted β-cell deletion of Pten lead to a significant increase in total islet mass. This phenotype was accompanied by an increase in peri-islet mitotic activity, particularly in islets injured by streptozotocin, a β cell-specific toxin.


CONCLUSIONS
Together with the in vitro observations, our data, here, suggest that that these mesenchymal cells may support the regeneration of the islets. Identifying how the communication occurs may provide clinically relevant mechanism for inducing β-cell regeneration.
From the *Departments of Pharmacology and Pharmaceutical Sciences, School of Pharmacy and †Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Jennifer-Ann
JA
Bayan
Zhechu
Z
Peng
Ni
N
Zeng
Lina
L
He
Jingyu
J
Chen
Bangyan L
BL
Stiles
D000199:Actins / Q000378:metabolism; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003893:Desmin / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D018345:Mice, Knockout; D008822:Mice, Transgenic; D058628:Myofibroblasts / Q000166:cytology / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics; D010179:Pancreas / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D058954:Pancreatic Stellate Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D051381:Rats; D012038:Regeneration / Q000502:physiology
D000199:Actins; D003893:Desmin; D051059:PTEN Phosphohydrolase