# Mesenchymal stem cell senescence in diabetic nephropathy

> **NIH NIH K23** · MAYO CLINIC  JACKSONVILLE · 2021 · $52,513

## Abstract

PROJECT SUMMARY/ABSTRACT
 I am a practicing nephrologist at Mayo Clinic and I will use the acquired skills from my clinical and
epidemiology background to bring the proposed basic research investigations into truly translational research
for patients with diabetic nephropathy (DN). I have assembled a multidisciplinary team of mentors who will
provide guidance, infrastructure, and tools needed for performance of the proposed studies. My immediate
career goal is to gain laboratory research skills, clinical trial experience, regenerative medicine fund-of-
knowledge, and regenerative medicine coursework. My long-term goal is to become a leader in Regenerative
Nephrology and an independent, productive clinician-investigator. My career development plan will provide me
with the building blocks needed to transition into independence. I have the strongest support from my division,
department, and institution. In the proposed studies, I will explore the feasibility of a novel therapeutic platform
that I believe may change the course of disease and improve the lives of patients with DN, a devastating
disease with few therapeutic options. Mesenchymal stromal/stem cell (MSC) transplantation offers hope.
MSCs are non-embryonic stem cells with anti-fibrotic, anti-inflammatory, and pro-angiogenic paracrine activity
that improve regeneration in DN models. Senescence is an irreversible cell cycle arrest, which generates a
pro-inflammatory secretory phenotype that impairs neighboring cell function. Hence, increased senescent cell
burden in DN may substantially compromise MSC function and become a barrier to successful autologous
MSC transplantation. Our overall goal is to characterize and optimize the functional properties of MSC in
DN to allow these patients to benefit from future enrollment in clinical trials using stem cell
transplantation. A central mechanism limiting MSC functional capacity, may be treatable through senolytic
drugs that selectively eliminate senescent cells. We will examine senolytic therapy as a potential in vivo
preconditioning method to improve stem cell function. Our central hypothesis is that adipose-derived MSC
obtained from DN patients show increased senescence and decreased functionality, which can be
ameliorated, both in vitro and in vivo, using drugs that clear senescent cells. First, we will compare
cellular senescence and functionality in MSC from DN patients to MSC from age- and gender-matched
controls. Second, we will incubate cells with senolytic agents in vitro and assess DN-MSC senescent cell
clearance and function thereafter. Third, we will conduct a pilot study wherein DN patients will receive
senolytic drugs, and MSC senescence and function will be measured at baseline and 14 days after treatment.
Additional examinations will include blood and urine collection for kidney function and injury measurements.
The proposed studies explore an innovative approach for preconditioning MSC and their deleterious
microenvironment, and a...

## Key facts

- **NIH application ID:** 10275178
- **Project number:** 3K23DK109134-05S1
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** LaTonya J Hickson
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $52,513
- **Award type:** 3
- **Project period:** 2016-07-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10275178

## Citation

> US National Institutes of Health, RePORTER application 10275178, Mesenchymal stem cell senescence in diabetic nephropathy (3K23DK109134-05S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10275178. Licensed CC0.

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