# AI-informed Signaling Factor Design for in vitro Rejuvenating Mesenchymal Stromal Cells

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $250,000

## Abstract

ABSTRACT
 While mesenchymal stromal cells (MSCs) hold great promise for treating many challenging diseases, a
major barrier to clinically meaningful MSC therapies is the inability to consistently produce potent MSCs. In vitro
cultured MSCs often rapidly enter senescence and lose their potency, driven largely by misregulated metabolic
signaling in culture. To address this, many signaling pathways (e.g., FGF, ATM, SRT, mTOR, EGF, DDR2) have
been identified as regulators of senescence-related processes. Building upon these discoveries, this R35 MIRA
project aims to develop an innovative approach to delay MSC senescence by collectively adjusting these
pathways.
 In this administrative supplement proposal, we aim to address an unexpected technical hurdle
encountered in the parent award and introduce an innovative research aim by acquiring the Nikon NSPARC
confocal imaging module. Over the past two years, our efforts to resolve recurring issues with our current
confocal system have been unsuccessful, leading us to rely on a suboptimal epifluorescent microscope for AI
training data. Following extensive research, we have identified the Nikon NSPARC module as the optimal
replacement, offering high-resolution and high-throughput imaging essential for detailed observation of
subcellular structures like mitochondria, endoplasmic reticulum, and histone marks. Its low phototoxicity also
makes it suitable for live cell imaging, allowing us to explore dynamic cellular information and enhance our AI
model’s prediction of cell senescence states. Overall, this supplementary application, seeking to acquire a Nikon
Spatial Array Confocal Module, aims to overcome an unexpected technical obstacle critical to fulfilling the
objectives of the parent award while also augmenting our imaging capacity to explore novel hypotheses in
deciphering metabolism-based senescence pathways and rejuvenation mechanisms.

## Key facts

- **NIH application ID:** 11094242
- **Project number:** 3R35GM146735-03S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Neil Lin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $250,000
- **Award type:** 3
- **Project period:** 2022-09-21 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11094242

## Citation

> US National Institutes of Health, RePORTER application 11094242, AI-informed Signaling Factor Design for in vitro Rejuvenating Mesenchymal Stromal Cells (3R35GM146735-03S2). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/11094242. Licensed CC0.

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