Biophysical, Molecular and Proteomic Profiling of Human Retinal Organoid-Derived Exosomes.

Humans Exosomes Proteomics Extracellular Vesicles / metabolism Retina Organoids / metabolism
Bioreactor Extracellular vesicles Human retinal organoids Proteomics Stem cells

Journal

Pharmaceutical research
ISSN: 1573-904X
Titre abrégé: Pharm Res
Pays: United States
ID NLM: 8406521

Informations de publication

Date de publication:
Apr 2023
Historique:
received: 11 05 2022
accepted: 23 07 2022
medline: 26 4 2023
pubmed: 25 8 2022
entrez: 24 8 2022
Statut: ppublish

Résumé

There is a growing interest in extracellular vesicles (EVs) for ocular applications as therapeutics, biomarkers, and drug delivery vehicles. EVs secreted from mesenchymal stem cells (MSCs) have shown to provide therapeutic benefits in ocular conditions. However, very little is known about the properties of bioreactor cultured-3D human retinal organoids secreted EVs. This study provides a comprehensive morphological, nanomechanical, molecular, and proteomic characterization of retinal organoid EVs and compares it with human umbilical cord (hUC) MSCs. The morphology and nanomechanical properties of retinal organoid EVs were assessed using Nanoparticle tracking analysis (NTA) and Atomic force microscopy (AFM). Gene expression analysis of exosome biogenesis of early and late retinal organoids were compared using qPCR. The protein profile of the EVs were analyzed with proteomic tools. NTA indicated the average size of EV as 100-250 nm. A high expression of exosome biogenesis genes was observed in late retinal organoids EVs. Immunoblot analysis showed highly expressed exosomal markers in late retinal organoids EVs compared to early retinal organoids EVs. Protein profiling of retinal organoid EVs displayed a higher differential expression of retinal function-related proteins and EV biogenesis proteins than hUCMSC EVs, implicating that the use of retinal organoid EVs may have a superior therapeutic effect on retinal disorders. This study provides supplementary knowledge on the properties of retinal organoid EVs and suggests their potential use in the diagnostic and therapeutic treatments for ocular diseases.

Identifiants

DOI: 10.1007/s11095-022-03350-7 PMID: 36002615 PMC: PMC10576571
pubmed: 36002615
doi: 10.1007/s11095-022-03350-7
pii: 10.1007/s11095-022-03350-7
pmc: PMC10576571
mid: NIHMS1835060
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

801-816

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS125016
Pays : United States
Organisme : NIMHD NIH HHS
ID : U54 MD007582
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY032197
Pays : United States
Organisme : NEI NIH HHS
ID : U24 EY029891
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015083
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105826
Pays : United States
Organisme : NIH HHS
ID : U24 EY029891
Pays : United States
Organisme : NIH HHS
ID : R01-NS125016
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY002162
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA102701
Pays : United States
Organisme : NIH HHS
ID : R01- EY032197
Pays : United States

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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Auteurs

Peggy Arthur (P)

College of Pharmacy and Pharmacological Sciences, Florida A&M University, Tallahassee, FL, USA.

Sangeetha Kandoi (S)

Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA.
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.

Li Sun (L)

Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL, USA.
Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA.

Anil Kalvala (A)

College of Pharmacy and Pharmacological Sciences, Florida A&M University, Tallahassee, FL, USA.

Shallu Kutlehria (S)

College of Pharmacy and Pharmacological Sciences, Florida A&M University, Tallahassee, FL, USA.

Santanu Bhattacharya (S)

Department of Biochemistry and Molecular Biology, Mayo College of Medicine and Science, Jacksonville, FL, USA.
Department of Physiology and Biomedical Engineering, Mayo College of Medicine and Science, Jacksonville, FL, USA.

Tanmay Kulkarni (T)

Department of Biochemistry and Molecular Biology, Mayo College of Medicine and Science, Jacksonville, FL, USA.

Ramesh Nimma (R)

College of Pharmacy and Pharmacological Sciences, Florida A&M University, Tallahassee, FL, USA.

Yan Li (Y)

Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL, USA. yli@eng.famu.fsu.edu.

Deepak A Lamba (DA)

Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA. deepak.lamba@ucsf.edu.

Mandip Singh (M)

College of Pharmacy and Pharmacological Sciences, Florida A&M University, Tallahassee, FL, USA. mandip.sachdeva@famu.edu.
ORCID: 0000-0001-6722-3709

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