Abstract:
Chronic pancreatitis (CP) is a debilitating disease characterized by irreversible morphological changes (fibrosis)
and persistent inflammation in the pancreas. Abdominal pain is one of the predominant symptoms and presents
in up to 90% of CP patients and is associated with the heavy use of opioids. Chronic pain can cause opioid
dependence, anxiety, depression and reduced quality of life. Although opioids are effective for acute pain, they
are not effective as a long-term treatment strategy. There is a critical need for more effective, safer, and non-
addictive therapeutic options for people who suffer from chronic pain associated with CP or other diseases.
The use of mesenchymal stromal cells (MSCs) in treating pain represents a promising novel intervention as
increasing evidence demonstrates that MSC therapy can effectively target several injury pathways in a variety
of fibroinflammatory diseases while reducing pain, something that most pharmacological interventions cannot
accomplish. MSCs exert protective effects through the release of pro-mitotic, antiapoptotic, anti-inflammatory,
and immunomodulatory soluble factors, to mitigate metabolomic and oxidative stress imbalance. Data from
animal models and clinical trials support the outstanding and durable effects of MSC infusion in the suppression
of chronic inflammation and neurological pain associated with various diseases. Our own animal study
demonstrated that MSC infusion significantly reduces pain and improves fibrosis and pancreatic volume in
mouse models of CP. However, whether the infusion of MSCs can be used as a novel approach to relieving
chronic pain and improve pancreatic function in CP patients has not been tested and will be the focus of this
study.
Based on compelling data, our hypothesis is that treatment with MSCs reduces chronic pain and improves
pancreatic fibrosis and function by their ability to target multiple injury pathways. The objective of this study is
two folds: (i) prepare for the clinical trial (UG3 phase, year 1), and determine the safety and efficacy of MSC
therapy in patients with painful CP (UH3 phase, year 2-5). Another critical part of the clinical trial phase will be
to define the mechanisms by which MSCs relieve multiple injuries in the pancreas by measuring changes of
peripheral blood mononuclear cells (PBMCs), especially monocyte subsets and serum proinflammatory cytokine
profiles of treated patients, with the goal of identifying biochemical pathways and serum biomarkers of response
to MSC therapy. This study may help develop novel non-addictive cellular therapy for chronic pancreatitis and
pain.
