Human bone marrow-derived clonal mesenchymal stem cells inhibit inflammation and reduce acute pancreatitis in rats.
OBJECTIVE
Acute pancreatitis (AP) has a high mortality rate; repetitive AP induces chronic AP and pancreatic adenocarcinoma. Mesenchymal stem cells (MSCs) have immunoregulatory effects and reduce inflammation. We developed a protocol to isolate human bone marrow-derived clonal MSCs (hcMSCs) from bone marrow aspirate and investigated the effects of these cells in rat models of mild and severe AP.


METHODS
Mild AP was induced in Sprague-Dawley rats by 3 intraperitoneal injections of cerulein (100 μg/kg), given at 2-hour intervals; severe AP was induced by intraparenchymal injection of 3% sodium taurocholate solution. hcMSCs were labeled with CM-1,1'-dioctadecyl-3,3,3'-tetramethylindo-carbocyanine perchloride and administered to rats through the tail vein.


RESULTS
hcMSCs underwent self-renewal and had multipotent differentiation capacities and immunoregulatory functions. Greater numbers of infused hcMSCs were detected in pancreas of rats with mild and severe AP than of control rats. Infused hcMSCs reduced acinar-cell degeneration, pancreatic edema, and inflammatory cell infiltration in each model of pancreatitis. The hcMSCs reduced expression of inflammation mediators and cytokines in rats with mild and severe AP. hcMSCs suppressed the mixed lymphocyte reaction and increased expression of Foxp3(+) (a marker of regulatory T cells) in cultured rat lymph node cells. Rats with mild or severe AP that were given infusions of hcMSCs had reduced numbers of CD3(+) T cells and increased expression of Foxp3(+) in pancreas tissues.


CONCLUSIONS
hcMSCs reduced inflammation and damage to pancreatic tissue in a rat model of AP; they reduced levels of cytokines and induced numbers of Foxp3(+) regulatory T cells. hcMSCs might be developed as a cell therapy for pancreatitis.
Department of Biomedical Sciences, College of Medicine, Inha University, Sinheung-dong, Jung-gu, Incheon, Republic of Korea.
Kyung Hee
KH
Jung
Sun U
SU
Song
Tacghee
T
Yi
Myung-Shin
MS
Jeon
Sang-Won
SW
Hong
Hong-Mei
HM
Zheng
Hee-Seung
HS
Lee
Myung-Joo
MJ
Choi
Don-Haeng
DH
Lee
Soon-Sun
SS
Hong
D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002108:Ceruletide; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018836:Inflammation Mediators / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D010179:Pancreas / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D010195:Pancreatitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012038:Regeneration; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology; D013656:Taurocholic Acid; D013997:Time Factors
D015415:Biomarkers; D017252:CD3 Complex; D016207:Cytokines; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D018836:Inflammation Mediators; D013656:Taurocholic Acid; D002108:Ceruletide