# An Innovative Two-Step Therapeutic Strategy to Maximize the Effect of Stem Cell Therapy for Post-Traumatic Osteoarthritis

> **NIH VA I01** · MEMPHIS VA MEDICAL CENTER · 2024 · —

## Abstract

PROJECT SUMMARY/ABSTRACT
 The etiology of osteoarthritis (OA) is multi-factorial. Abnormal and excessive cumulative joint stress results
in post-traumatic osteoarthritis (PTOA). Approximately 30% of knee OA in Veterans is attributable to
occupational activities, particularly jobs requiring kneeling or squatting in combination with heavy lifting, such
as sport activity injuries. Currently, there is no effective therapy for OA patients. Recently, the stem cell therapy
has shown promise to regenerate the damaged joint tissue. In our previous study, adipose-derived stem cells
(ASCs) show great promise as therapeutic agents in regenerative medicine because of their multi-lineage
potential, immunosuppressive activities, limited immunogenicity, and relative ease of growth in culture.
However, there are several concerns that impede the clinical use of stem cell therapy in the inflammatory joint
environment such as apoptosis, dosing, timing of intervention, homing efficacy, and route of delivery of ASCs.
We have also found that NF-κB inhibitors such as TPCA-1 decrease inflammation in mechanically injured knee
joints using our established PTOA mouse model and in vitro model.
 In this project, we aim our studies based on two points: 1) Pre-treatment of exogenously derived ASCs with
antioxidant (such as Vitamin-E) before injection into the joint can lead to cyto-protective effects and resistance
to apoptosis and toxic inflammatory factors after transplantation. 2) TPCA1-nanosome can improve the harsh
condition in the arthritic knee joint by anti-inflammatory mechanism before transplantation of an exogenous
stem cell. Therefore, we will show the synergistic effect of this two-step therapeutic application (anti-
inflammatory nanosome treatment of the arthritic joint followed by transplantation of the Preconditioned ASCs).
 We have two aims: (1) Investigate the cytoprotective effects and therapeutic potential of preconditioned
ASCs in a model of PTOA. In this aim, we will investigate the therapeutic effect of the antioxidant (Vit-E-Ns)
pre-treated ASCs in vivo using our PTOA mouse model of knee overloading. In order to tailor this approach to
the appropriate veteran population (active vs retired) we will use aged mice to investigate whether they exhibit
different healing responses and mechanisms relative to younger mice. We will confirm the persistence of the
ASCs in the joint, correlating implantation levels with the reduction and repair of damaged cartilage as well as
optimizing the cell number and treatment interval. We will examine localization of the ASCs in the joint and
assess joint inflammation and cartilage integrity. We will investigate treatment-associated changes in the
biomechanical properties of subchondral bone and cartilage and its effects on pain-related behavior through
functional analyses. We will also investigate the recovery mechanism using an ASC-chondrocyte co-culture
system. (2) Demonstrate the synergistic therapeutic efficacy of the two...

## Key facts

- **NIH application ID:** 10816489
- **Project number:** 5I01RX004283-02
- **Recipient organization:** MEMPHIS VA MEDICAL CENTER
- **Principal Investigator:** Hongsik Jake Cho
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10816489

## Citation

> US National Institutes of Health, RePORTER application 10816489, An Innovative Two-Step Therapeutic Strategy to Maximize the Effect of Stem Cell Therapy for Post-Traumatic Osteoarthritis (5I01RX004283-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10816489. Licensed CC0.

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