# Generation and Validation of Disease Models for Port-Wine Birthmarks

> **NIH NIH R21** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2024 · $158,983

## Abstract

Project Summary Vascular malformations (VMs) are resulted from developmental abnormalities
in vasculatures including veins, arteries, capillaries, and lymphatic vessels. Treatment of VMs is
a big challenge due to the large variety of lesion types, complexity of symptoms, and limited
interventional options, which results in unsatisfied therapeutic outcomes. Port Wine Birthmarks
(PWB) is one of the most common types of VMs. It mainly appears on the face and can be highly
associated with Sturge Weber Syndrome (SWS) with brain blood vessels’ involvement and
seizure disorders. One long-term obstacle to our understanding of the disease causes of PWB
and the therapeutic development for it has been a lack of clinically relevant cell and animal models.
In this proposal, we will take advantages of utilizing our current advancements in the generation
of PWB-derived induced pluripotent stem cells (IPSCs) and their differentiated lineages such as
endothelial cells (ECs) and vascular spheroids/organoids (VSs). VSs derived from PWB show
larger diameters, longer lengths, and more tortuous branches as compared to the VSs derived
from normal IPSCs. In addition, such vascular phenotypes can be reproduced in vivo after an
implantation of spheroids/organoids into the mouse skin. These proof-of-principle and feasibility
studies let us propose to develop in vitro and in vivo clinically relevant cell and organoid models
derived from PWB patient’s IPSCs and validate them subsequently. For evaluation of in vitro cell
and organoid models, we will perform a series of molecular and phenotypic characterizations of
ECs and VSs derived from PWB IPSCs as compared to normal IPSCs. Furthermore, next
generation sequencing approaches will be used to explore and integrate the molecular, epigenetic,
and signaling pathway profiles that underlie the abnormal cell-fate and lineage-specification in
PWB. These molecular pathological features will be further validated with PWB skin lesions. For
evaluation of the in vivo model, we will implant VSs into skins in mice, monitor and characterize
the dynamics of the vasculature formation and remodeling. We will determine the recapitulated
PWB pathologies in this in vivo model as compared to the existing data from PWB skin lesions.
The project is highly innovative as it aims to develop clinically relevant and paradigm-shift cell and
organoid models for mechanistic and therapeutic studies of PWB. The use of patient-derived
IPSCs, ECs, and VSs are unprecedented; the data is translational. These models are not only a
significant evolution in disease model development for understanding of pathological
characteristics of PWB, but also a substantial advancement in development of a novel platform
for clinical therapeutic studies.

## Key facts

- **NIH application ID:** 10891726
- **Project number:** 5R21AR083066-02
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Wenbin Tan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $158,983
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891726

## Citation

> US National Institutes of Health, RePORTER application 10891726, Generation and Validation of Disease Models for Port-Wine Birthmarks (5R21AR083066-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10891726. Licensed CC0.

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