# Hypoxic preconditioning for the improvement of the regenerative capacity of adipose-derived mesenchymal stem cells and its application in chronic kidney disease due to hypertensive nephropathy

> **NIH NIH K08** · MAYO CLINIC ROCHESTER · 2020 · $159,660

## Abstract

PROJECT SUMMARY/ABSTRACT
Hypertensive Nephropathy (HN) is the second leading cause of chronic kidney disease (CKD) resistant to
effective intervention to prevent progression. However, recent advances in regenerative medicine with the use
of adipose tissue-derived mesenchymal stromal/stem cell (AD-MSC) transplantation offer hope for these
patients. The MSCs have anti-fibrotic, anti-inflammatory, and pro-angiogenic paracrine activities that improve
regeneration in some kidney injury models. However, exposure to patient-specific factors, such as aging and
the uremic milieu of CKD in HN, may exert epigenetic and transcriptional modulation of MSC, potentially
modifying their phenotype to one noxious to neighboring cells. Hence, increased cellular damage in HN may
substantially compromise MSC function and become a barrier to successful autologous MSC transplantation.
Our central hypothesis underlying this proposal is that MSCs obtained from patients with HN show impaired
functionality and angiogenesis, which can be modified with hypoxic preconditioning (HPC). This hypothesis will
be addressed both in vitro and in vivo in three specific aims: 1) we will compare functionality of MSCs from
patients with HN (eGFR 15-60 mL/min/1.73m2) to MSC from age- and sex-matched patients with hypertension
and healthy controls; 2) to determine the reversibility of HN-MSC dysfunction, we will subject cells from these
cohorts to HPC in vitro and assess MSC function thereafter; and 3) to examine the effect of MSC function in
vivo, we will conduct an experimental study in a porcine renovascular hypertension model that recapitulates
the pathophysiology of HN, six-weeks after induction of renal artery stenosis. These pigs, as well as normal
age-matched pigs, will be treated with HPC-MSC, untreated-MSC, or vehicle. To assess the impact of HPC on
MSC potency, renal hemodynamics, function, and oxygenation will be studied after four-weeks, using
sophisticated in vivo CT and MR imaging techniques, and renal injury and vascularity studied ex vivo. The
significance of the proposed studies is high, since developing a safe and effective therapy to delay HN
progression could reduce morbidity associated with dialysis, offer a better treatment option to a population
often deferred for kidney transplantation, and produce extensive cost savings. These novel studies will
advance the knowledge of the effects of HPC on MSC and their deleterious microenvironment, aid in
developing a completely novel therapeutic strategy to delay the progression of HN supporting the NIDDK
mission. The proposed project addresses how characterize and improve the functional properties of MSC in
HN to allow these patients to benefit from future enrollment in clinical trials using stem cell transplantation. The
exceptional resources and institutional support at Mayo Clinic, outstanding multi-disciplinary mentorship team,
and proposed career development activities will allow the candidate to achieve her long-term goa...

## Key facts

- **NIH application ID:** 9942422
- **Project number:** 5K08DK118120-03
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Sandra M Herrmann
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $159,660
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942422

## Citation

> US National Institutes of Health, RePORTER application 9942422, Hypoxic preconditioning for the improvement of the regenerative capacity of adipose-derived mesenchymal stem cells and its application in chronic kidney disease due to hypertensive nephropathy (5K08DK118120-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9942422. Licensed CC0.

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