Multiplexed analysis of neural cytokine signaling by a novel neural cell–cell interaction microchip

Abdullah, Mohammed A. A.; Amini, Nooshin; Yang, Liwei; Paluh, Janet L.; Wang, Jun

doi:10.1039/d0lc00401d

Cited by 7 publications

(10 citation statements)

References 59 publications

(69 reference statements)

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“…To increase stem cell studies that reflect ethnic diversity (ED) in the United States, we analyzed EMLO gastruloids using previously derived hiPSC lines from our laboratory 11 , 12 , 14 – 16 . Nine ED-hiPSC lines derived from the fibroblasts of three donors of self-designated African American (F3.5.2, F3.2.2, F3.3.1), Hispanic-Latino (H3.3.1, H3.1.1, H3.4.1), and Asian (A2.1.1, A2.2.1, A2.2.2) ethnicities were compared (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Co-development of central and peripheral neurons with trunk mesendoderm in human elongating multi-lineage organized gastruloids

Olmsted

Paluh

2021

Nat Commun

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Stem cell technologies including self-assembling 3D tissue models provide access to early human neurodevelopment and fundamental insights into neuropathologies. Gastruloid models have not been used to investigate co-developing central and peripheral neuronal systems with trunk mesendoderm which we achieve here in elongating multi-lineage organized (EMLO) gastruloids. We evaluate EMLOs over a forty-day period, applying immunofluorescence of multi-lineage and functional biomarkers, including day 16 single-cell RNA-Seq, and evaluation of ectodermal and non-ectodermal neural crest cells (NCCs). We identify NCCs that differentiate to form peripheral neurons integrated with an upstream spinal cord region after day 8. This follows initial EMLO polarization events that coordinate with endoderm differentiation and primitive gut tube formation during multicellular spatial reorganization. This combined human central-peripheral nervous system model of early organogenesis highlights developmental events of mesendoderm and neuromuscular trunk regions and enables systemic studies of tissue interactions and innervation of neuromuscular, enteric and cardiac relevance.

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Section: Resultsmentioning

confidence: 99%

Co-development of central and peripheral neurons with trunk mesendoderm in human elongating multi-lineage organized gastruloids

Olmsted

Paluh

2021

Nat Commun

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“…hiPSC lines were previously reprogrammed from the fibroblasts of three individuals from samples banked at Coriell 10 and were extensively characterized by our laboratory 11,13,14 . Coriell donor catalog numbers are as follows: GM22268 (F-3; African American male, foreskin, 1 day); AG08498 (A-2; Asian male, foreskin, 1 day); GM22186 (H-3; Hispanic-Latino male, foreskin, 1 day).…”

Section: Human Ethnically-diverse Hipsc Lines and Culture Conditionsmentioning

confidence: 99%

“…Details of ED-hiPSC characterization are provided in Supplementary Table 1. hiPSCs were maintained in pluripotency medium mTeSR Plus (STEMCELL Technologies) supplemented with 1x penicillin-streptomycin (P-S) on hESC- 43 and spinal motor neurons 13,14 were derived similarly to as previously described. For nociceptor sensory neurons, hiPSCs were seeded onto freshly-coated Matrigel 20,000-40,000 cells/cm 2 in mTeSR Plus with 10 μM Y-27632.…”

Section: Human Ethnically-diverse Hipsc Lines and Culture Conditionsmentioning

confidence: 99%

“…Our unique EMLO approach with human stem cells is an important step towards heterogenous 3D culture platforms with increased complexity and reproducibility that better reflects closely linked human developmental processes in vitro, and which is likely to benefit organ innervation studies. that reflect ethnic diversity (ED) in the U.S., we analyzed EMLO gastruloids using previously derived hiPSC lines from our laboratory 10,11,[13][14][15] . Nine ED-hiPSC lines derived from the fibroblasts of three donors of self-designated African American (F3.…”

Section: Introductionmentioning

confidence: 99%

“…Beginning at day 4, N2 supplement was added every other day at 25% increments to day 10. At day 20, cultures were maintained in BrainPhys supplemented with N2/B27 and 10 ng/ml BDNF, 10 ng/ml GDNF (R&D Systems), 1 μM dibutyryl-cyclic AMP (dbcAMP).For spinal motor neurons, restricted neuromesodermal progenitors (NMps) were induced in 2D adherent hiPSC colonies (~60% confluency) by culture in N2B27 supplemented with 40 ng/ml FGF2, 40 ng/ml FGF8 (R&D Systems), 2 μM CHIR 99021, 10 μM DAPT (Tocris Bioscience), 10 μM SB 431542, 100 nM LDN 193189, 0.36 U/ml heparin13,14 (Millipore Sigma).Medium was changed daily for four days. At day 4, NMps were split in N2B27 supplemented with 100 nM RA, 200 nM Hh-Ag1.5 and maintained to day 20 at which point, BrainPhyssupplemented medium described above was added.…”

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confidence: 99%

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Integrating central and peripheral neurons in elongating multi-lineage-organized gastruloids

Olmsted

Paluh

2020

Preprint

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Human stem cell technologies including self-assembling 3D tissue models provide unprecedented access to early neurodevelopment and enable fundamental insights into neuropathologies. Gastruloid models have yet to be used to investigate the developing nervous system. Here we generate elongating multi-lineage-organized (EMLO) gastruloids with trunk identity that co-develop central and peripheral nervous system (CNS, PNS) correlates. We track migrating neural crest cells that differentiate to form peripheral neurons integrated with an upstream spinal cord region. This follows initial EMLO polarization events, and is coordinated with primitive gut tube elongation and cardiomyocyte differentiation. By immunofluorescence of multi-lineage and functional biomarkers, we evaluate EMLOs over a twenty-two day period, and apply them to investigate the impact of mu opioid receptor modulation on neuronal activity. This comprehensive study demonstrates a novel combined CNS-PNS model of early organogenesis and integration events in the trunk to benefit human biomedical research.

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Sensor‐integrated brain‐on‐a‐chip platforms: Improving the predictive validity in neurodegenerative research

Spitz,

Schobesberger,

Brandauer

et al. 2023

Bioengineering & Transla Med

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Affecting millions of individuals worldwide, neurodegenerative diseases (NDDs) pose a significant and growing health concern in people over the age of 60 years. Contributing to this trend are the steady increase in the aging population coupled with a persistent lack of disease‐altering treatment strategies targeting NDDs. The absence of efficient therapeutics can be attributed to high failure rates in clinical trials and the ineptness of animal models in preceding preclinical studies. To that end, in recent years, significant research effort has been dedicated to the development of human cell‐based preclinical disease models characterized by a higher degree of predictive validity. However, a key requirement of any in vitro model constitutes the precise knowledge and replication of the target tissues' (patho‐)physiological microenvironment. Herein, microphysiological systems have demonstrated superiority over conventional static 2D/3D in vitro cell culture systems, as they allow for the emulation and continuous monitoring of the onset, progression, and remission of disease‐associated phenotypes. This review provides an overview of recent advances in the field of NDD research using organ‐on‐a‐chip platforms. Specific focus is directed toward non‐invasive sensing strategies encompassing electrical, electrochemical, and optical sensors. Additionally, promising on‐ and integrable off‐chip sensing strategies targeting key analytes in NDDs will be presented and discussed in detail.

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Multiplexed analysis of neural cytokine signaling by a novel neural cell–cell interaction microchip

Abstract: Multipotent neural stem cells (NSCs) are widely applied in pre-clinical and clinical trials as a cell source to promote tissue regeneration in neurodegenerative diseases. Frequently delivered as dissociated cells, aggregates...

Cited by 7 publications

References 59 publications

Co-development of central and peripheral neurons with trunk mesendoderm in human elongating multi-lineage organized gastruloids

Co-development of central and peripheral neurons with trunk mesendoderm in human elongating multi-lineage organized gastruloids

Integrating central and peripheral neurons in elongating multi-lineage-organized gastruloids

Sensor‐integrated brain‐on‐a‐chip platforms: Improving the predictive validity in neurodegenerative research

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