Kidney Week

Abstract: TH-PO0576

MOTS-c Pretreatment Ameliorates the Cardioprotective Effects of Mesenchymal Stem/Stromal Cells Harvested from Patients with Obesity

Session Information

• Development, Stem Cells, and Regenerative Medicine
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 600 Development, Stem Cells, and Regenerative Medicine

Authors

• Yoon, Se-Hee, Mayo Clinic Minnesota, Rochester, United States

Se-Hee Yoon, MD, PhD

• Lu, Bo, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Bo Lu, MD

• Xing, Li, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Li Xing

• Zhang, Lei, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Lei Zhang, MD, PhD

• Zhu, Xiang yang, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Xiang yang Zhu, MD, PhD

• Tang, Hui, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Hui Tang

• Kumagai, Hiroshi, University of Southern California, Los Angeles, California, United States

Hiroshi Kumagai, PhD

• Miller, Brendan, University of Southern California, Los Angeles, California, United States

Brendan Miller, PhD

• Eirin, Alfonso, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Alfonso Eirin, MD

• Lerman, Amir, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Amir Lerman, MD

• Cohen, Pinchas, University of Southern California, Los Angeles, California, United States

Pinchas Cohen, MD

• Lerman, Lilach O., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Lilach O. Lerman, MD, PhD, FASN

Background

Mitochondrial open-reading frame of the 12S ribosomal RNA type-c (MOTS-c) has anti-inflammatory and metabolic benefits. Mesenchymal stem/stromal cells (MSCs) offer treatment potential via direct cellular interactions and paracrine effects, including extracellular vehicles (EVs). However, MSC and EV potency in subjects with obesity is blunted, partly due to mitochondrial impairment. We hypothesized that a fall of MOTS-c expression in adipose tissue-derived (AT)-MSC from obese patients contributes to their dysfunction in renovascular hypertensive (RVH) mice.

Methods

AT-MSCs were isolated from subcutaneous fat of obese and age-matched lean subjects during bariatric or kidney-donation surgeries, respectively. EVs were obtained from AT-MSC preconditioned with 10µM MOTS-c or vehicle for 48h. Two weeks after RVH intra-aortic AT-MSC or EVs were delivered in mice. Two weeks later cardiac function was assessed in-vivo by MRI, and hearts studied ex-vivo.

Results

MOTS-c expression was markedly decreased in Obese-MSCs, associated with impaired mitochondrial function. Co-incubation restored MOTS-c levels. RVH-induced cardiac hypertrophy and myocardial damage was attenuated by lean but not obese-MSCs or obese-EVs. MOTS-c preconditioning partially restored obese-AT-MSCs functions, preventing blood pressure elevation, reducing hypertrophy, and improving myocardial vascularization and redox status.

Conclusion

Downregulation of MOTS-c in obese-MSCs in part impairs the reparative capacity of obesity-derived AT-MSCs. MOTS-c replenishment may enhance endogenous repair and autologous cell-based therapies in obesity.

Figure. MOTS-c effects in RVH.
(A) DHE staining (B) CD31 staining (C) VEGF mRNA n=5–8/group. Mean±SD. *P<.05, **P<.01, ***P<.001.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20257sdt3xp9