# Reconstructing native soluble cues in vascularized whole lung scaffolds

> **NIH NIH R00** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $248,999

## Abstract

Project Abstract
 Diseases of the lung vasculature, including capillary leak syndrome/acute respiratory distress syndrome
(ARDS), inhalation injury, primary pulmonary hypertension, and the novel coronavirus disease-19 (COVID-19),
are difficult to study due to the lack of functional ex vivo models. Conventional culture systems are typically
limited in their ability to represent human pathophysiology for the study of disease and drug mechanisms. The
overall objective of this proposal is to develop an experimental platform that mimics the pulmonary
microvasculature, and that can simulate native cellular phenotypes and functions in vitro, during normal
homeostasis and during disease states such as severe inflammation, and sepsis. The lung microvascular
niche characteristics, such as paracrine factors, hemodynamics, and extracellular matrix composition are all of
pivotal importance for regulating endothelial maturation and maintaining vascular homeostasis. Whole organ
decellularization opens a door to provide a construct that recapitulates the substrate structure and components
of an entire vascular tree. Additionally, leveraging single-cell RNA-seq (scRNAseq), we developed
computational tools to identify the paracrine signals in human distal lungs. In this study, I will leverage these
tools to identify novel, important locally acting soluble factors in a functional lung microvascular niche to
improve pulmonary microvascular maturation in acellular lung scaffolds. During the K99 phase of this proposal,
I will first leverage our published scRNAseq computational tools to evaluate the scRNAseq dataset on native
adult human lungs. I will determine a group of important and novel soluble factors that could improve
endothelial maturation. Then, I will rationally iterate on our endothelial repopulated lung platform with the
addition of relevant soluble factors derived from the native microvascular milieu. During the R00 phase, I will
use the vascular platform established in prior aims and start to develop a disease modeling system to study the
impact of inflammation for drug testing. This work will lead to the creation of a novel platform which, unlike
previous microvascular platforms, specifically resembles many physiological aspects of the native lung
environment. Such a platform could be used for pulmonary vascular disease modeling and drug testing.

## Key facts

- **NIH application ID:** 10896273
- **Project number:** 5R00HL159261-04
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Yifan Yuan
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $248,999
- **Award type:** 5
- **Project period:** 2023-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896273

## Citation

> US National Institutes of Health, RePORTER application 10896273, Reconstructing native soluble cues in vascularized whole lung scaffolds (5R00HL159261-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10896273. Licensed CC0.

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