Amniotic fluid-derived stem cells: potential factories of natural and mimetic strategies for congenital malformations.

Autor: Fonteles CSR; Departamento de Clínica Odontológica. Faculdade de Farmácia, Odontologia E Enfermagem, Universidade Federal Do Ceara. Rua Monsenhor Furtado, S/N-Rodolfo Teófilo, Fortaleza, Brazil., Enterria-Rosales J; Center for Precision Environmental Health, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA., Lin Y; Center for Precision Environmental Health, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA., Steele JW; Center for Precision Environmental Health, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA., Villarreal-Leal RA; Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.; Escuela de Medicina y Ciencias de La Salud, Tecnologico de Monterrey, Monterrey, Mexico., Xiao J; Center for Precision Environmental Health, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA., Idowu DI; Center for Precision Environmental Health, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA., Burgelin B; Center for Precision Environmental Health, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA., Wlodarczyk BJ; Center for Precision Environmental Health, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA., Finnell RH; Center for Precision Environmental Health, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA.; Departments of Molecular and Human Genetics Molecular & Cellular Biology and Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA., Corradetti B; Center for Precision Environmental Health, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA. bruna.corradetti@bcm.edu.; Department of Medicine, Section Oncology/Hematology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA. bruna.corradetti@bcm.edu.
Jazyk: angličtina
Zdroj: Stem cell research & therapy [Stem Cell Res Ther] 2024 Dec 05; Vol. 15 (1), pp. 466. Date of Electronic Publication: 2024 Dec 05.
DOI: 10.1186/s13287-024-04082-8
Abstrakt: Background: Mesenchymal stem cells (MSCs) derived from gestational tissues offer a promising avenue for prenatal intervention in congenital malformations although their application is hampered by concerns related to cellular plasticity and the need for invasive, high-risk surgical procedures. Here, we present naturally occurring exosomes (EXOs) isolated from amniotic fluid-derived MSCs (AF-MSCs) and their mimetic analogs (MIMs) as viable, reproducible, and stable alternatives. These nanovesicles present a minimally invasive therapeutic option, addressing the limitations of MSC-based treatments while retaining therapeutic efficacy.
Methods: MIMs were generated from AF-MSCs by combining sequential filtration steps through filter membranes with different porosity and size exclusion chromatography columns. A physicochemical, structural, and molecular comparison was conducted with exosomes (EXOs) released from the same batch of cells. Additionally, their distribution patterns in female mice were evaluated following in vivo administration, along with an assessment of their safety profile throughout gestation in a mouse strain predisposed to neural tube defects (NTDs). The possibility to exploit both formulations as mRNA-therapeutics was explored by evaluating cell uptake in two different cell types(fibroblasts, and macrophages) and mRNA functionality overtime in an in vitro experimental setting as well as in an ex vivo, whole embryo culture using pregnant C57BL6 dams.
Results: Molecular and physiochemical characterization showed no differences between EXOs and MIMs, with MIMs determining a threefold greater yield. Biodistribution patterns following intraperitoneal administration were comparable between the two particle types, with the uterus being among targeted organs. No toxic effects were observed in the dams during gestation, nor were there any malformations or significant differences in the number of viable versus dead fetuses detected. MIMs delivered a more intense and prolonged expression of mRNA encoding for green fluorescent protein in macrophages and fibroblasts. An ex-vivo whole embryo culture demonstrated that MIMs mainly accumulate at the level of the yolk sac, while EXOs reach the embryo.
Conclusions: The present data confirms the potential application of EXOs and MIMs as suitable tools for prevention and treatment of NTDs and proposes MIMs as prospective vehicles to prevent congenital malformations caused by in utero exposure to drugs.
Competing Interests: Declarations. Conflict of interest: Richard H. Finnell was formerly associated with TeratOmic Consulting, a now defunct organization. He also receives travel funds for editorial board meetings of the journal Reproductive and Developmental Medicine. Ethical approval and consent to participate: Ex vivo studies were conducted following the approved protocol #AN-7618 established by Baylor College of Medicine’s Institutional Animal Care and Use Committee (IACUC) in accordance with the guidelines of the Animal Welfare Act and the Guide for the Care and Use of Laboratory Animals, as well as adhering to the ARRIVE guidelines 2.0. Animal protocol title “Intervention strategies for non-folate responsive neural tube defects”, approval date 11/17/2023. In vivo studies were conducted following approved protocol #AN-9175 entitled “Biomimetic therapeutics for congenital malformations”, approval date 10/04/2023. Human amniotic fluid stem cells were procured from Cellprogen. The human tissues used by Celprogen for isolation of cell cultures is ethically sourced under IRB protocols, with informed donor consent, and in compliance with HIPAA, HITECH, the Declaration of Helsinki, the European Convention on Human Rights and Biomedicine, and the UK's Human Tissue Act (as reported in the Celprogen Biomedical Ethical Standards document ( https://celprogen.com ). Consent for publication: All authors confirm their consent for publication.
(© 2024. The Author(s).)
Databáze: MEDLINE
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