3D bioprinting of biomimetic acute myeloid leukemia disease models

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Project Description

Acute Myeloid Leukemia (AML) is a hematological malignancy of bone marrow (BM) origin characterized by the clonal expansion and differentiation arrest of myeloid progenitor cells. Worldwide the incidence of AML has been steadily increasing over the last three decades. AML remains a therapeutic challenge due to its high heterogeneity, with various subclones possessing distinct genetic and epigenetic alterations contributing to tumor functional differences such as drug resistance. We have developed a unique class of ultrashort self-assembling peptide hydrogels and proven in previous studies the potential use of these biomaterials as a 3D culture system for various cell types. This study aims to develop a 3D AML "organoid" model using advanced self-assembling peptides and patient-derived cellular components: primarily, establishing a model that closely recapitulates the tumor microenvironment and can be used in drug screening applications to enable personalized medicine therapeutics; ultimately, providing a platform that can help in answering unresolved questions regarding tumor development and niche organization.
Program - BioEngineering
Division - Biological and Environmental Sciences and Engineering
Field of Study - blood cancer, tissue engineering, nanomedicine, materials science

About the
Researcher

Charlotte Hauser

Charlotte Hauser

Desired Project Deliverables

1. Identification and formulation of self-assembling peptide for the fabrication of 3D biomimicry models representative of the leukemic bone marrow niche i. Design and synthesis of suitable peptides and functionalization with bioactive moieties ii. Cytocompatibility testing of peptide hydrogel scaffolds iii. Establishment of 3D AML in vitro culture models 2. Investigation of leukemia microenvironment role on disease development and progression i. Investigation of exosomes role in tumor microenvironment regulation ii. Investigation of stromal cells role in tumor microenvironment regulation 3. Evaluation (Validation) of the 3D AML models as an in vitro model for drug screening i. Assessment of the effectiveness of the developed 3D biomimicry AML models in drug screening ii. Gene expression analysis and biomarkers identification