# Ex Vivo Generation of Functional  Kidney Tissues for Transplantation

> **NIH NIH UC2** · HARVARD UNIVERSITY · 2021 · $790,327

## Abstract

PROJECT SUMMARY
In the U.S. alone, up to 26 million people have chronic kidney disease, over 460,000 people are on dialysis, and
100,000 people await kidney transplants with 3,000 new patients added monthly. Given the growing lack of
transplantable organs, patients typically require renal replacement therapies that themselves lead to substantial
morbidity and mortality. We posit that biomanufactured kidney tissues, and ultimately, organs may offer an
important solution to this growing problem. Indeed, recent protocols in developmental biology are unlocking the
potential for stem cells to undergo differentiation and self-assembly to form “mini-organs”, known as organoids.
Kidney organoids exhibit remarkable tissue microarchitectures with high cellular density and heterogeneity akin
to their in vivo counterparts. To bridge the gap from these kidney organoid building blocks (OBBs) to therapeutic
organs, integrative approaches that combine bottom-up organoid assembly with top-down bioprinting are
needed. While it is difficult, if not impossible, to imagine how either organoids or bioprinting alone would fully
replicate the complex multiscale features required for kidney function – their combination could provide an
enabling foundation for de novo organ manufacturing. To generate 3D functional kidney tissues ex vivo for
potential transplantation, our highly collaborative research team will undertake two primary aims. In Specific Aim
1, we will create kidney organoids enhanced by multilineage induction that display functional differentiation of
nephrons. We will produce iPSC-derived kidney organoids and subject them to fluid flow during their
differentiation and maturation on an adherent extracellular matrix (ECM). Through multilineage induction, we will
also induce collecting duct cells that self-assemble and structurally bridge other tubular nephron segments. We
will evaluate the effects of mimicking kidney organogenesis on kidney organoid structure and function using
microperfusion and micropuncture methods. In Specific Aim 2, we will create 3D functional kidney tissues
composed of these optimized kidney OBBs with embedded macrochannels produced by bioprinting that serve
as both vascular and urinary output conduits. We will first produce a densely cellular, tissue matrix composed of
kidney OBBs that facilitates bioprinting of embedded macrochannels. We will then establish connections
between the printed macrochannels embedded in this OBB-laden matrix and the self-assembled microvascular
and collecting duct networks within individual OBBs. Finally, we will assess the glomerular filtration, tubular
maturation, and primitive urinary production of these 3D kidney tissues. If successful, our proposed project will
provide a foundational advance in kidney organ engineering for potential renal therapeutic applications.

## Key facts

- **NIH application ID:** 10248544
- **Project number:** 5UC2DK126023-02
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Jennifer A. Lewis
- **Activity code:** UC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $790,327
- **Award type:** 5
- **Project period:** 2020-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248544

## Citation

> US National Institutes of Health, RePORTER application 10248544, Ex Vivo Generation of Functional  Kidney Tissues for Transplantation (5UC2DK126023-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10248544. Licensed CC0.

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