# Engineering the Stem Cell Microenvironment for Lymphatic Regeneration

> **NIH NIH R35** · UNIVERSITY OF NOTRE DAME · 2021 · $391,250

## Abstract

ABSTRACT
The lymphatic system is an integral part of the circulatory system, where extracellular fluid flows from vascular
capillaries into the lymphatic vessels and is returned to the vascular system via the thoracic duct. Additionally,
lymphatic vessels regulate homeostasis of tissue fluid, absorption of dietary fat, and trafficking of immune cells.
Consequently, dysfunction in lymphatic vessels is associated with development of many diseases, including
obesity and metabolic disease, aging and Alzheimer’s disease, chronic wound and cancer, as well as
inflammation and cardiovascular diseases. Therefore, controlling lymphatic vascular formation and augmenting
its function is postulated as a promising therapeutic target for preventing and treating these debilitating diseases.
Unfortunately, therapeutic lymphangiogenesis has not been widely explored partly due to the unavailability of a
clinically-relevant cell source and controllable matrix environment. The overall goal of the research program is
to derive lymphatic endothelial cells (LECs) and lymphatic muscle cells (LMCs) from human pluripotent stem
cells (hPSCs) that can be used as a clinically-relevant cell source for modeling lymphatic function and physiology,
as well as therapeutic lymphangiogenesis in a synthetic and controllable matrix environment. To this end, our
lab is at the forefront of developing multi-disciplinary approaches to utilize stem cells and synthetic biomaterials
for basic understanding of stem cell differentiation and lymphatic vessel morphogenesis, as well as approaches
in therapeutic lymphangiogenesis. We have recently established xeno-free, well-defined and controllable
differentiation protocols to direct hPSCs differentiation to clinically-relevant vascular progenitor cells with high
reproducibility and efficiency, as well as wide clinical applicability. Furthermore, synthetic matrices can be used
to provide spatial and temporal control for these progenitor cells to undergo lymphatic vascular morphogenesis,
useful for basic understanding of lymphatic vascular biology and a range of therapeutic applications. These
results establish a fundamental link between vascular and lymphatic morphogenesis within synthetic matrices.
We are currently focused on bridging the large knowledge gap between molecular understanding of vascular
and lymphatic differentiation and morphogenesis in a developmental context. Furthermore, we are also testing
the impact of lymphatic vasculature to attenuate inflammatory response, prevent edema, and eventually promote
tissue regeneration in a wound healing model. Cumulatively, we are combining approaches in stem cell and
bioengineering, biomaterials and microfluidics, as well as lymphatic and systems biology to develop the
necessary component in therapeutic lymphangiogenesis: reliable human cell sources from hPSCs within a
biologically rational synthetic and controllable matrix environment. Collectively, this research has the potential to
not only ...

## Key facts

- **NIH application ID:** 10276874
- **Project number:** 1R35GM143055-01
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Donny Hanjaya-Putra
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $391,250
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10276874

## Citation

> US National Institutes of Health, RePORTER application 10276874, Engineering the Stem Cell Microenvironment for Lymphatic Regeneration (1R35GM143055-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10276874. Licensed CC0.

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