Bioengineered optogenetic model of human neuromuscular junction.

Disease modeling Human tissue models Myasthenia gravis Neuromuscular junction Optogenetics iPS cells

Journal

Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316

Informations de publication

Date de publication:
09 2021
Historique:
received: 17 02 2021
revised: 09 07 2021
accepted: 15 07 2021
pubmed: 18 8 2021
medline: 21 9 2021
entrez: 17 8 2021
Statut: ppublish

Résumé

Functional human tissues engineered from patient-specific induced pluripotent stem cells (hiPSCs) hold great promise for investigating the progression, mechanisms, and treatment of musculoskeletal diseases in a controlled and systematic manner. For example, bioengineered models of innervated human skeletal muscle could be used to identify novel therapeutic targets and treatments for patients with complex central and peripheral nervous system disorders. There is a need to develop standardized and objective quantitative methods for engineering and using these complex tissues, in order increase their robustness, reproducibility, and predictiveness across users. Here we describe a standardized method for engineering an isogenic, patient specific human neuromuscular junction (NMJ) that allows for automated quantification of NMJ function to diagnose disease using a small sample of blood serum and evaluate new therapeutic modalities. By combining tissue engineering, optogenetics, microfabrication, optoelectronics and video processing, we created a novel platform for the precise investigation of the development and degeneration of human NMJ. We demonstrate the utility of this platform for the detection and diagnosis of myasthenia gravis, an antibody-mediated autoimmune disease that disrupts the NMJ function.

Identifiants

pubmed: 34403849
pii: S0142-9612(21)00389-6
doi: 10.1016/j.biomaterials.2021.121033
pmc: PMC8439334
mid: NIHMS1733333
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

121033

Subventions

Organisme : NHLBI NIH HHS
ID : P01 HL089707
Pays : United States
Organisme : NIEHS NIH HHS
ID : U01 ES032673
Pays : United States
Organisme : NIBIB NIH HHS
ID : UH3 EB025765
Pays : United States
Organisme : NIBIB NIH HHS
ID : UG3 EB025765
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135358
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB027062
Pays : United States

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

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Auteurs

Olaia F Vila (OF)

Columbia University, 622 W 168th St, New York, NY, 10032, USA; Gladstone Institutes, 1650 Owens St, San Francisco, CA, 94158, USA. Electronic address: olaia.vila@gladstone.ucsf.edu.

Miguel Chavez (M)

Columbia University, 622 W 168th St, New York, NY, 10032, USA.

Stephen P Ma (SP)

Columbia University, 622 W 168th St, New York, NY, 10032, USA.

Keith Yeager (K)

Columbia University, 622 W 168th St, New York, NY, 10032, USA.

Lyandysha V Zholudeva (LV)

Gladstone Institutes, 1650 Owens St, San Francisco, CA, 94158, USA.

Jennifer M Colón-Mercado (JM)

National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, 20892, USA.

Yihuai Qu (Y)

Columbia University, 622 W 168th St, New York, NY, 10032, USA.

Trevor R Nash (TR)

Columbia University, 622 W 168th St, New York, NY, 10032, USA.

Carmen Lai (C)

Gladstone Institutes, 1650 Owens St, San Francisco, CA, 94158, USA.

Carissa M Feliciano (CM)

Gladstone Institutes, 1650 Owens St, San Francisco, CA, 94158, USA; Department of Pediatrics, UCSF, 550 16th St, Floor 5, San Francisco, CA, 94143, USA.

Matthew Carter (M)

Gladstone Institutes, 1650 Owens St, San Francisco, CA, 94158, USA.

Roger D Kamm (RD)

Department of Mechanical Engineering and Biological Engineering, Massachusetts Institute of Technology, Cambridge MA, 02139, USA.

Luke M Judge (LM)

Gladstone Institutes, 1650 Owens St, San Francisco, CA, 94158, USA; Department of Pediatrics, UCSF, 550 16th St, Floor 5, San Francisco, CA, 94143, USA.

Bruce R Conklin (BR)

Gladstone Institutes, 1650 Owens St, San Francisco, CA, 94158, USA.

Michael E Ward (ME)

National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, 20892, USA.

Todd C McDevitt (TC)

Gladstone Institutes, 1650 Owens St, San Francisco, CA, 94158, USA.

Gordana Vunjak-Novakovic (G)

Columbia University, 622 W 168th St, New York, NY, 10032, USA. Electronic address: gv2131@columbia.edu.

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Classifications MeSH