# Enhancing vascular delivery of stem cells and microparticles

> **NIH NIH R01** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2020 · $371,503

## Abstract

In order for vascularly infused stem cells to reach targeted organ for repair or circulating tumor cells to leave
the primary site for metastasis, the first step is that the cells need to transmigrate across the blood vessel wall.
Although such transmigration does occur, the exact mechanism is elusive. It has been postulated that the
injected stem cells or circulating tumor cells undergo a process similar to leukocytes or white blood cells,
termed diapedesis. In this process, white blood cells in the lumen squeeze through the endothelial barrier of
the blood vessel into the surrounding tissue. However, our lab has discovered injected cells undergo an
extravasation process distinct significantly from diapedesis. We have named this new extravasation process
Angiopellosis (“angio”: relating to blood vessels; “pello”: push, drive out). During the angiopellosis process, the
vascular wall undergoes extensive remodeling to allow the cell to exit the lumen, while the cell itself remains
distinctively passive in activity. Angiopellosis supports the group extravasation phenomenon that does not fit
the conventional diapedesis theory. Our central hypothesis is that alterations in cell clustering and molecular
pathways involved in angiopellosis can significantly change the efficiency of cell extravasation, impacting the
safety and efficacy of stem cell transplantation and increasing understanding of cancer cell metastasis. Our
preliminary data suggests adhesion molecules such as integrins and secreted proteins such as matrix
metalloproteinases are critical to angiopellosis. In this grant study, we plan to employ in vitro blood vessel
models and in vivo zebrafish and mouse models of vasculatures to study angiopellosis, with state-of-art
imaging techniques and series of gain- and loss-of-function experiments. AIM 1 is to decipher the molecular
control of the angiopellosis process in injected stem cells and cancer cells. AIM 2 is to test the ability of
angiopellosis agonists to improve infused stem cell engraftment/efficacy. AIM 3 is to examine the potential of
angiopellosis-enabling microparticles for extravasation and regeneration in heart injury. Our study will provide
new insights on cell extravasation and complement the current solitary diapedesis theory. Together, the
proposed mechanistic and translational experiments will provide a scientific premise to understand cell
extravasation while suggesting targets for therapeutic intervention and promoting stem cell transplantation
technologies.

## Key facts

- **NIH application ID:** 9904748
- **Project number:** 5R01HL137093-04
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Ke Cheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,503
- **Award type:** 5
- **Project period:** 2017-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9904748

## Citation

> US National Institutes of Health, RePORTER application 9904748, Enhancing vascular delivery of stem cells and microparticles (5R01HL137093-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9904748. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*