Influence of Stem Cell Therapy on Thyroid Function and Reactive Oxygen Species Production in Diabetic Rats

Diorney Luiz Souza Gran da Silva; Mariana Lopes de Freitas; Gustavo Monnerat Cahil; Vitória Santório de São José; Felippe Mousovich Neto; Ricardo Cortez Cardoso; Vânia Maria Correa da Costa; Rodrigo Soares Fortunato; Denise Pires de Carvalho; Emiliano Horácio Medei; Andrea Claudia Freitas Ferreira

doi:10.1055/a-0588-7944

Hormone and Metabolic Research, Inhaltsverzeichnis

Horm Metab Res 2018; 50(04): 331-339
DOI: 10.1055/a-0588-7944

Endocrine Research

Influence of Stem Cell Therapy on Thyroid Function and Reactive Oxygen Species Production in Diabetic Rats

Autor*innen

Diorney Luiz Souza Gran da Silva

¹Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Mariana Lopes de Freitas

¹Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Gustavo Monnerat Cahil

²Laboratory of Cardiac Electrophysiology, IBCCF, UFRJ, Rio de Janeiro, Brazil
Vitória Santório de São José

²Laboratory of Cardiac Electrophysiology, IBCCF, UFRJ, Rio de Janeiro, Brazil
Felippe Mousovich Neto

¹Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Ricardo Cortez Cardoso

¹Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Vânia Maria Correa da Costa

¹Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Rodrigo Soares Fortunato

³Laboratory of Molecular Radiobiology, IBCCF, UFRJ, Rio de Janeiro, Brazil
Denise Pires de Carvalho

¹Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Emiliano Horácio Medei

²Laboratory of Cardiac Electrophysiology, IBCCF, UFRJ, Rio de Janeiro, Brazil
Andrea Claudia Freitas Ferreira

¹Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

⁴Campus Duque de Caxias, NUMPEX-Bio, UFRJ, Rio de Janeiro, Brazil

Abstract

Cell therapy with mesenchymal stem cells (MSC) has been proposed for the treatment of diabetes mellitus (DM). It is known that the prevalence of thyroid disease is higher among diabetic patients than in general population. Therefore, our aim was to investigate the effect of the treatment with MSC on thyroid function and ROS generation in an experimental model of type 1 DM. Adult male Wistar rats were divided into the following groups: control, DM (80 mg/kg BW streptozotocin, iv.) and DM+MSC. MSC treatment occurred 4 weeks after DM induction and the animals were euthanized 4 weeks after MSC administration. We also evaluated the effect of co-culture with MSC or extracellular vesicles (EV) obtained from these cells on the rat thyroid cell line PCCL3 exposed to high glucose. Thyroid H₂O₂ generation was increased in DM, which was reversed by MSC treatment. These changes paralled a significant DuOx1 mRNA increase. The incubation of PCCL3 with high glucose increased extracellular H₂O₂ generation, which was reversed by both the co-culture with MSC and EV. Even though MSC treatment normalized thyroid ROS generation, serum thyroid hormone (TH) concentration remained low, along with increased serum TSH concentrations. Thyroperoxidase (TPO) activity, was reduced in DM, and MSC treatment did not normalize TPO. Therefore, we conclude that the treatment with MSC was able to reverse the increased thyroid H₂O₂ generation in diabetic animals and in PCCL3 cells exposed to high glucose, an effect probably mediated by EV produced by these cells, acting in a paracrine fashion.

Key words

reactive oxygen species - thyroperoxidase - mesenchymal stem cells - diabetes mellitus

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Referenzen

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