Modeling Down Syndrome Myeloid Leukemia by Sequential Introduction of and Mutations in Induced Pluripotent Stem Cells with Trisomy 21.

Children with Down syndrome (DS) have a high risk for acute myeloid leukemia (DS-ML). Genomic characterization of DS-ML blasts showed the presence of unique mutations in , an essential hematopoietic transcription factor, leading to the production of a truncated from of GATA1 (GATA1s). GATA1s, together with trisomy 21, is sufficient to develop a pre-leukemic condition called transient abnormal myelopoiesis (TAM).

Harnessing the Power of Induced Pluripotent Stem Cells and Gene Editing Technology: Therapeutic Implications in Hematological Malignancies.

In vitro modeling of hematological malignancies not only provides insights into the influence of genetic aberrations on cellular and molecular mechanisms involved in disease progression but also aids development and evaluation of therapeutic agents. Owing to their self-renewal and differentiation capacity, induced pluripotent stem cells (iPSCs) have emerged as a potential source of short in supply disease-specific human cells of the hematopoietic lineage. Patient-derived iPSCs can recapitulate the disease severity and spectrum of prognosis dictated by the genetic variation among patients and can be used for drug screening and studying clonal evolution.

A 3-D hydrogel based system for hematopoietic differentiation and its use in modeling down syndrome associated transient myeloproliferative disorder.

Induced pluripotent stem cells (iPSCs) provide an extraordinary tool for disease modeling owing to their potential to differentiate into the desired cell type. The differentiation of iPSCs is typically performed on 2-dimensional monolayers of stromal cell or animal tissue derived extracellular matrices. Recent advancements in disease modeling have utilized iPSCs in 3-dimensional (3D) cultures to study diseases such as muscular dystrophy, cardiomyopathy, and pulmonary fibrosis.

The extracellular matrix: A key player in the pathogenesis of hematologic malignancies.

Hematopoietic stem and progenitor cells located in the bone marrow lay the foundation for multiple lineages of mature hematologic cells. Bone marrow niches are architecturally complex with specific cellular, physiochemical, and biomechanical factors. Increasing evidence suggests that the bone marrow microenvironment contributes to the pathogenesis of hematological neoplasms.

Modeling Transient Abnormal Myelopoiesis Using Induced Pluripotent Stem Cells and CRISPR/Cas9 Technology.

Approximately 1%-2% of children with Down syndrome (DS) develop acute myeloid leukemia (AML) prior to age 5 years. AML in DS children (ML-DS) is characterized by the pathognomonic mutation in the gene encoding the essential hematopoietic transcription factor , resulting in N-terminally truncated short form of GATA1 (GATA1s). Trisomy 21 and GATA1s together are sufficient to induce transient abnormal myelopoiesis (TAM) exhibiting pre-leukemic characteristics.

Biocompatibility and Viscoelastic Properties of Injectable Resilin-Like Polypeptide and Hyaluronan Hybrid Hydrogels in Rabbit Vocal Folds.

Vocal fold scar, characterized by alterations in the lamina propria extracellular matrix, disrupts normal voice quality and function. Due to a lack of satisfactory clinical treatments, there is a need for tissue engineering strategies to restore voice. Candidate biomaterials for vocal fold tissue engineering must match the unique biomechanical and viscoelastic properties of native tissue without provoking inflammation.

Microstructured Elastomer-PEG Hydrogels via Kinetic Capture of Aqueous Liquid-Liquid Phase Separation.

Heterogeneous hydrogels with desired matrix complexity are studied for a variety of biomimetic materials. Despite the range of such microstructured materials described, few methods permit independent control over microstructure and microscale mechanics by precisely controlled, single-step processing methods. Here, a phototriggered crosslinking methodology that traps microstructures in liquid-liquid phase-separated solutions of a highly elastomeric resilin-like polypeptide (RLP) and poly(ethylene glycol) (PEG) is reported.

Thiol-ene Photocrosslinking of Cytocompatible Resilin-Like Polypeptide-PEG Hydrogels.

A range of chemical strategies have been used for crosslinking recombinant polypeptide hydrogels, although only a few have employed photocrosslinking approaches. Here, we capitalize on the novel insect protein, resilin, and the versatility of click reactions to introduce a resilin-like polypeptide (RLP) that is capable of photoinitiated thiol-ene crosslinking. Lysine residues of the RLP were functionalized with norbornene acid as confirmed via 1H-NMR spectroscopy.