# Role of early life hyperoxia on mesenchymal stem cell fate: their impact on age related disease

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2022 · $192,500

## Abstract

PROJECT SUMMARY
 Exposure to environmental pollutants or toxins early in life can alter health and fitness as people age.
Preterm infants are a prime example because their lungs are exposed too soon and often to excess amounts of
oxygen at birth. These individuals are then at risk for growth failure, reduced lung function, impaired host
response to respiratory viral infections, and development of cardiovascular disease as they age. We established
a unique mouse model wherein exposure to high levels of oxygen (hyperoxia) at birth causes lung and heart
disease later in life. Using this model, we now provide new evidence that neonatal hyperoxia also impairs growth
by inhibiting fat accumulation. Bone marrow mesenchymal stem cells (BMSCs) isolated from these mice grew
slower and were more oxidized. They also displayed reduced capacity to accumulate lipid and differentiate into
adipocytes, possibly because they expressed higher levels of 5’-AMP activated protein kinase (AMPK), a master
regulator of energy homeostasis that inhibits fatty acid synthesis and cell proliferation. Since the oxidation of
stem cells increases with age, we will test the hypothesis that neonatal hyperoxia accelerates the oxidation
of mesenchymal stem cells as mice age, thereby altering their ability to differentiate and produce fat. In
Aim 1, we will determine how neonatal hyperoxia permanently reprograms the oxidation state and thus
differentiation of bone, fat, and lung MSCs. Since growth failure is not seen when transgenic SftpcEC-SOD mice
are exposed to hyperoxia, Aim 2 will determine if over-expression of the anti-oxidant extracellular superoxide
dismutase by alveolar epithelial type 2 cells restores the oxidation state and adipogenic potential of MSCs. We
will also determine whether EC-SOD preserves the differentiation of adjacent lipofibroblasts that support AT2
cell homeostasis. Impact on the Field: Understanding how neonatal hyperoxia disrupts adipogenesis is
important because it will increase our understanding of how preterm birth alters health later in life.

## Key facts

- **NIH application ID:** 10475250
- **Project number:** 5R21AG070585-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Michael A O'Reilly
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475250

## Citation

> US National Institutes of Health, RePORTER application 10475250, Role of early life hyperoxia on mesenchymal stem cell fate: their impact on age related disease (5R21AG070585-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10475250. Licensed CC0.

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