# Engineering the Organizer

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $225,936

## Abstract

Project Summary:
Regeneration and development operate on the sub-millimeter scale, using evolved design principles to
drive self-assembly of replacement and new organs. Our goal with this project is to follow the principle of
'the organizer', where a small group of cells are microsurgically grafted into a naive host tissues to pattern and
induce organ primordia from the naive tissue. To achieve this we first identify methods to produce stable
laminar sheets of naive tissue (i.e. stable host tissues), and to develop novel tools to assemble these laminar
sheets, (i.e. in place of manual microsurgical grafts) to enable formation of planar polarized 3D structures. The
principles that propel modern tissue engineering are based on classic embryological studies of morphogenesis
in organoids. These classic studies relied on amphibian models where specified cells could be isolated from
embryos, formed into aggregates, and differentiated into distinctive tissues. Following programs of sorting and
engulfment, and differentiation, cells self-assemble planar, polarized laminar sheets with distinct polarity, e.g.
anterior-to-posterior, to form tissues consisting of multiple cell types at high cell density. It is now widely
recognized that similar, conserved programs of self-assembly shape human tissues during embryogenesis,
regeneration, and cancer progression. However, current efforts to engineer complex 3D structures suffer from
an inability to reproducibly and reliably generate organized multi-laminar tissues of multiple cell types at high
cell density. To date, no tissue engineering approach is capable of recreating multi-laminar polarized 3D
structures analogous to those that form at even the earliest stages in the embryo. Using our experience with
and expertise in embryonically assembled tissues, we leverage principles of the organizer, and engineer stable
multi-laminar tissues with planar polarity. Based on our published methods for shaping 3D embryonic tissues
into laminar sheets, we will to expose the cellular that stabilize those sheets and to develop assembly methods
to produce planar polarized tissues. Rapid translation to human biomedical research and tissue are made
possible by leveraging the speed and accessibility of the amphibian embryonic model to test and translate key
findings to human embryonic stem cell models of the organizer. We envision that the long term outcome of this
project will transform efforts to engineer and manufacture tissues that can be sourced from human cell types
and iPSCs for a wide range of clinical and research applications.

## Key facts

- **NIH application ID:** 10317741
- **Project number:** 1R21HD106629-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** LANCE A. DAVIDSON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $225,936
- **Award type:** 1
- **Project period:** 2021-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317741

## Citation

> US National Institutes of Health, RePORTER application 10317741, Engineering the Organizer (1R21HD106629-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10317741. Licensed CC0.

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