Distinct and Shared Determinants of Cardiomyocyte Contractility in Multi-Lineage Competent Ethnically Diverse Human iPSCs

Tomov, Martin L.; Olmsted, Zachary T.; Dogan, Haluk; Gongorurler, Eda; Tsompana, Maria; Otu, Hasan H.; Buck, Michael; Chang, Eun Ah; Cibelli, José B.; Paluh, Janet L.

doi:10.1038/srep37637

Cited by 23 publications

(35 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1 b) by targeting Wnt and FGF signaling using established methods 5 , 17 , 18 , with the well-characterized hiPSC line F3.5.2 developed in our laboratory (Fig. 1 c–e) 19 , 20 . The GSK-3β inhibitor small molecule CHIR99021 and FGF2/FGF8 recombinant proteins were used to induce SOX2+/Brachyury+ NMps.…”

Section: Resultsmentioning

confidence: 99%

“…The self-designated African American human iPSC line F3.5.2 was previously developed by the Paluh and Cibelli labs using lentivirus transduction of donor fibroblasts with Yamanaka factors and extensively characterized 19 , 20 . Here, F3.5.2 was maintained in mTeSR1 or mTeSR Plus complete growth medium (STEMCELL Technologies) with 1 × penicillin–streptomycin (P-S; Gibco) on hESC-qualified Corning Matrigel substrate (37 °C, 5% CO 2 ).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Fabrication of homotypic neural ribbons as a multiplex platform optimized for spinal cord delivery

Olmsted

Stigliano

Badri

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

cell therapy for the injured spinal cord will rely on combined advances in human stem cell technologies and delivery strategies. Here we encapsulate homotypic spinal cord neural stem cells (scnScs) in an alginate-based neural ribbon delivery platform. We perform a comprehensive in vitro analysis and qualitatively demonstrate graft survival and injury site retention using a rat C4 hemi-contusion model. Pre-configured neural ribbons are transport-stable modules that enable site-ready injection, and can support scNSC survival and retention in vivo. Neural ribbons offer multifunctionality in vitro including co-encapsulation of the injury site extracellular matrix modifier chondroitinase ABC (chABC), tested here in glial scar models, and ability of cervically-patterned scNSCs to differentiate within neural ribbons and project axons for integration with 3-D external matrices. This is the first extensive in vitro characterization of neural ribbon technology, and constitutes a plausible method for reproducible delivery, placement, and retention of viable neural cells in vivo.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Fabrication of homotypic neural ribbons as a multiplex platform optimized for spinal cord delivery

Olmsted

Stigliano

Badri

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Generation of cervical SMNs from hiPSCs using trunk-biased developmental neuromesodermal progenitors. Spinal motor neurons (SMNs) were derived from the African American hiPSC line F3.5.2 (Chang et al, 2015;Tomov et al, 2016) in three stages ( Fig. 1 and 2), here referred to as (1) neural induction, (2) caudo-ventral patterning, and (3) neuronal maturation.…”

Section: Resultsmentioning

confidence: 99%

Neuromesodermal Progenitors Advance Network Formation of Spinal Neurons and Support Cells in Neural RibbonsIn Vitroand Unprotected Survival in a Rat Subacute Contusion Model

Stigliano

Scimemi

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Improved human stem cell interventions to treat CNS trauma requires continued expansion of in vitro models and delivery platforms to fill gaps in analysis and treatment. Transplanted neural stem cells (NSCs) face unique, multi-faceted challenges beyond survival that include differentiation, maturation, and integration into a complex cytokine-releasing microenvironment that impinges on a multipotent cell type. Alternate strategies to transplant neurons and neuronal networks deserve reevaluation, particularly since novel differentiation protocols mimicking region-specific developmental and positional cues have recently emerged. To investigate transplantation of neurons and their early networks, we generate in vitro neural ribbons containing spinal neurons and support cells anatomically matched for cervical spinal cord injury (SCI). These glutamate-responsive, electrically-active neural ribbons apply a new hiPSC differentiation strategy transiting through neuromesodermal progenitors (NMps) to derive developmentally relevant spinal motor neurons (SMNs), interneurons (INs), and oligodendrocyte progenitor cells (OPCs). Bioinformatic profiling validates region-specific identities. Neurons and neuronal networks are functionally evaluated for action potential firing, calcium signaling, population activity, and synaptogenesis. NMp-derived neurons survive in vivo within the subacute phase hemi-contusion injury cavity when delivered either as free suspension or as encapsulated networks of pre-formed CNS cytoarchitectures. Delivery as encapsulated networks further supports survival of lower cell numbers and rapid graft penetration into host tissue. Neural network ribbons therefore provide a novel intermediary approach between cell suspensions and complex organoids for investigating network formation and early transplantation events with hiPSC-derived neurons, providing flexibility to rapidly tune cell type(s), cell ratios, and traceable biomarkers.Significance StatementIn the two decades since human stem cell technologies have emerged, the challenge has remained to improve the developmentally relevant derivation of therapeutic cells. The ability to now generate anatomically matched neurons for SCI necessitates a re-evaluation of these cells and their networks in vitro and in vivo. In this study, we apply developmental cues via neuromesodermal progenitors to generate spinal neurons from hiPSCs. Genetic and functional evaluation of these cells as in vitro neuronal networks, due to their capacity to survive and graft effectively within the rat subacute contusion cavity, offer novel approaches for customizing SCI transplantation. This work demonstrates a strategy to develop transplantable, chemically-responsive networks linking in vitro models with injury customization towards improved in vivo outcomes.

show abstract

“…Cell Self-Assembly Approaches-Cell self-assembly utilizes the inherent ability of the cells to organize in tissue-specific manner to recapitulate the desired tissue/organ structure. Such bottom-up approaches that exploit autonomous cell aggregation can significantly facilitate engineering of functional cardiovascular tissues [80]. As cardiac patches for treating myocardial infarct (MI), self-assembled cell sheet constructs have demonstrated engraftment associated with CM proliferation, neovascularization, and intercellular junctions [81][82][83][84][85].…”

Section: Hybrid (Cellular Scaffold) Approachesmentioning

confidence: 99%

Engineering Functional Cardiac Tissues for Regenerative Medicine Applications

et al. 2019

Self Cite

View full text Add to dashboard Cite

Purpose of Review Tissue engineering has expanded into a highly versatile manufacturing landscape that holds great promise for advancing cardiovascular regenerative medicine. In this review, we provide a summary of the current state-of-the-art bioengineering technologies used to create functional cardiac tissues for a variety of applications in vitro and in vivo. Recent Findings Studies over the past few years have made a strong case that tissue engineering is one of the major driving forces behind the accelerating fields of patient-specific regenerative medicine, precision medicine, compound screening, and disease modeling. To date, a variety of approaches have been used to bioengineer functional cardiac constructs, including biomaterialbased, cell-based, and hybrid (using cells and biomaterials) approaches. While some major progress has been made using cellular approaches, with multiple ongoing clinical trials, cell-free cardiac tissue engineering approaches have also accomplished multiple breakthroughs, although drawbacks remain. Summary This review summarizes the most promising methods that have been employed to generate cardiovascular tissue constructs for basic science or clinical applications. Further, we outline the strengths and challenges that are inherent to this field as a whole and for each highlighted technology.

show abstract

Distinct and Shared Determinants of Cardiomyocyte Contractility in Multi-Lineage Competent Ethnically Diverse Human iPSCs

Cited by 23 publications

References 84 publications

Fabrication of homotypic neural ribbons as a multiplex platform optimized for spinal cord delivery

Fabrication of homotypic neural ribbons as a multiplex platform optimized for spinal cord delivery

Neuromesodermal Progenitors Advance Network Formation of Spinal Neurons and Support Cells in Neural RibbonsIn Vitroand Unprotected Survival in a Rat Subacute Contusion Model

Engineering Functional Cardiac Tissues for Regenerative Medicine Applications

Contact Info

Product

Resources

About