# hAAT-engineered Mesenchymal Stem Cells for the Treatment of Chronic Pain

> **NIH VA I01** · RALPH H JOHNSON VA MEDICAL CENTER · 2021 · —

## Abstract

Chronic pain is one of the most frequently reported conditions in Veterans and is now ruled by the court as a
VA disability. There is a significant interaction between chronic pain, post-traumatic stress disorder (PTSD),
and persistent post-concussive syndromes common to the veteran population. Therefore, the VA healthcare
mission to explore novel strategies to reduce chronic pain is vital. Chronic pain falls into two most common
classifications including nociceptive and neuropathic pains. The majority of chronic pain disorders start off with
a nociceptive source, although it is not uncommon for someone to have multiple pain conditions . Chronic
pancreatitis (CP) is an inflammatory disease of
the pancreas characterized by irreversible fibrosis, pancreas
atrophy, and exocrine dysfunction. Pain suffered by CP patients is among the worst encountered in medicine.
Chronic pain in the VA population and patients with CP share common underlying mechanisms, which are
inflammation and altered nociceptor transmission in peripheral neurons. CP pain therefore provides a useful
model for the understanding and treatment of pain syndromes with an identifiable nociceptive source in
general. Although current therapy provides relief to acute pain, drugs used for treatment of chronic pain are
typically less efficacious and limited by many side effects. The use of mesenchymal stem cells (MSCs) and
other anti-inflammatory agent such as human alpha-1 antitrypsin (AAT), as therapeutic tools are novel
therapies to treat chronic pain. In our previous studies we found that MSC infusion or treatment with hAAT
reduced pain and mitigated pancreas inflammation and disease progression in mouse models of CP. To
enhance the functionality of MSCs and to effectively deliver AAT locally into the pancreas in a sustainable
fashion, we engineered human AAT (hAAT) overexpressing MSCs by transfecting MSCs with a lentivirus
encoding the hAAT gene. hAAT-MSCs showed better migration ability, increased stemness and secretion of
AAT and other factors critical for MSC function compared to vector-treated control MSCs. Based on these
data, we hypothesize that hAAT-MSC infusion is an effective therapy for the treatment of CP and its associated
pain by inhibition of immune cell activation and suppression of nociceptor activation. The overall objective of
this study is to determine, in a pre-clinical rodent model of painful CP, the therapeutic and mechanistic impact
of hAAT-MSCs in inflammation reduction and pain relief and explore their potential translation to human
therapy using samples collected from patients with painful CP.

## Key facts

- **NIH application ID:** 10044402
- **Project number:** 5I01BX004536-02
- **Recipient organization:** RALPH H JOHNSON VA MEDICAL CENTER
- **Principal Investigator:** Hongjun Wang
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-10-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10044402

## Citation

> US National Institutes of Health, RePORTER application 10044402, hAAT-engineered Mesenchymal Stem Cells for the Treatment of Chronic Pain (5I01BX004536-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10044402. Licensed CC0.

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