**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Mª del Pilar Montero-Calle, Biomedical Engineering Program, Enabling Technologies Division, CIMA Universidad de Navarra, Foundation for Applied Medical Research, Pamplona, Spain.

**Main Body of the Abstract**
Introduction: Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a life-threatening disease currently lacking an optimal therapy, stemming from the absence of representative models. Our work aims to stablish for the first time an all-human 3D model of ATTR-CM where the main cellular and extracellular players of the pathology are present.
Methodology: A human induced pluripotent stem cell (hiPSC) line was derived from a patient carrying a p.Ser43Asn TTR mutation and differentiated into hepatocytes (hiPSC-HEPs), cardiomyocytes (hiPSC-CMs) and cardiac fibroblasts (hiPSC-CFs). Cells were embedded in a hydrogel (tailored for each cell type) and combined with a designed 3D printed scaffold using Melt Electro Writing (MEW) technology. Tissues were maintained in culture for up to 4 weeks and characterized by staining, albumin production, electrophysiological, plus genomic analysis. Exposure to TTR fibrils (TTR-FIB) was evaluated.
Results: Human hepatic and cardiac functional tissues can be generated using MEW-designs. These constructs exhibited albumin production and an active spontaneous contraction, respectively. Moreover, tissues displayed well distributed cells throughout the 3D-structure, positive for specific hepatic and cardiac mature markers. Interestingly, electrophysiological analysis showed that cardiac tissues displayed shortened calcium transients after TTR-FIB exposure compared to unexposed tissues. However, no differences were found in terms of beat rate, metabolic activity and gene expression for the concentrations used.
Conclusion: We have developed an advanced model of ATTR-CM capable of recapitulating the multisystem complexity of the disease, which will contribute to advancing our understanding of the mechanisms of the disease, and help discovering and formulating new treatments.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Mª del Pilar Montero-Calle, Biomedical Engineering Program, Enabling Technologies Division, CIMA Universidad de Navarra, Foundation for Applied Medical Research, Pamplona, Spain.

**Main Body of the Abstract**
**Introduction:** Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a life-threatening disease currently lacking an optimal therapy, stemming from the absence of representative models. Our work aims to stablish for the first time an all-human 3D model of ATTR-CM where the main cellular and extracellular players of the pathology are present.
**Methodology:** A human induced pluripotent stem cell (hiPSC) line was derived from a patient carrying a p.Ser43Asn TTR mutation and differentiated into hepatocytes (hiPSC-HEPs), cardiomyocytes (hiPSC-CMs) and cardiac fibroblasts (hiPSC-CFs). Cells were embedded in a hydrogel (tailored for each cell type) and combined with a designed 3D printed scaffold using Melt Electro Writing (MEW) technology. Tissues were maintained in culture for up to 4 weeks and characterized by staining, albumin production, electrophysiological, plus genomic analysis. Exposure to TTR fibrils (TTR-FIB) was evaluated.
**Results:** Human hepatic and cardiac functional tissues can be generated using MEW-designs. These constructs exhibited albumin production and an active spontaneous contraction, respectively. Moreover, tissues displayed well distributed cells throughout the 3D-structure, positive for specific hepatic and cardiac mature markers. Interestingly, electrophysiological analysis showed that cardiac tissues displayed shortened calcium transients after TTR-FIB exposure compared to unexposed tissues. However, no differences were found in terms of beat rate, metabolic activity and gene expression for the concentrations used.
**Conclusion:** We have developed an advanced model of ATTR-CM capable of recapitulating the multisystem complexity of the disease, which will contribute to advancing our understanding of the mechanisms of the disease, and help discovering and formulating new treatments.



Engineering hiPSC-Derived Tissue Models for Advanced Amyloidosis Research and Therapy Development PB10 (#293)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.