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A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells

Chow, Rebecca P; Nguyen, Kevin; Gou, Wenyu; Green, Erica; Morgan, Katherine; Lancaster, William; Helke, Kristi; Strange, Charlie; Wang, Hongjun
Chronic pancreatitis (CP) is characterized by pancreatic inflammation, fibrosis, and abdominal pain that is challenging to treat. Mesenchymal stromal cells (MSCs) overexpressing human alpha-1 antitrypsin (hAAT-MSCs) showed improved mobility and protective functions over native MSCs in nonobese diabetic mice. We investigated whether hAAT-MSCs could mitigate CP and its associated pain using trinitrobenzene sulfonic acid (TNBS)-induced CP mouse models. CP mice were given native human MSCs or hAAT-MSCs (0.5 × 106 cells/mouse, i.v., n = 6-8/group). The index of visceral pain was measured by graduated von Frey filaments. Pancreatic morphology and pancreatic mast cell count were analyzed by morphological stains. Nociceptor transient receptor potential vanilloid 1 (TRPV1) expression in dorsal root ganglia (DRG) was determined by immunohistochemistry. hAAT-MSC-treated CP mice best preserved pancreatic morphology and histology. MSC or hAAT-MSC infusion reduced abdominal pain sensitivities. hAAT-MSC therapy also suppressed TRPV1 expression in DRG and reduced pancreatic mast cell density induced by TNBS. Overall, hAAT-MSCs reduced pain and mitigated pancreatic inflammation in CP equal to MSCs with a trend toward a higher pancreatic weight and better pain relief in the hAAT-MSC group compared to the MSC group. Both MSCs and hAAT-MSCs might be used as a novel therapeutic tool for CP-related pain.
PMCID:8615652
PMID: 34829924
ISSN: 2227-9059
CID: 5928432

JOURNAL OF GASTROINTESTINAL SURGERY [Review]

Adams, David; Stocker, Abigail; Lancaster, William; Abell, Thomas
ISI:000592131800001
ISSN: 1091-255x
CID: 5928532

SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES

Kim, Doris; Gedney, Ryan; Allen, Shelby; Zlomke, Haley; Winter, Elizabeth; Craver, John; Pinnola, A. D.; Lancaster, Will; Adams, David
ISI:000567762000008
ISSN: 0930-2794
CID: 5928542

Surgical Management of Iatrogenic Bile Duct Injury in Patients with Atypical Ductal Anatomy [Case Report]

Hite, Melissa; Chung, Catherine; Lancaster, William
PMID: 32106916
ISSN: 1555-9823
CID: 5928382