Enhancement of the immunoregulatory potency of mesenchymal stromal cells by treatment with immunosuppressive drugs.
Cytotherapy
; 17(9): 1188-99, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-26276002
ABSTRACT
BACKGROUND AIMS:
Multipotent mesenchymal stromal cells (MSCs) are distinguished by their ability to differentiate into a number of stromal derivatives of interest for regenerative medicine, but they also have immunoregulatory properties that are being tested in a number of clinical settings.METHODS:
We show that brief incubations with rapamycin, everolimus, FK506 or cyclosporine A increase the immunosuppressive potency of MSCs and other cell types.RESULTS:
The treated MSCs are up to 5-fold more potent at inhibiting the induced proliferation of T lymphocytes in vitro. We show that this effect probably is due to adsorption of the drug by the MSCs during pre-treatment, with subsequent diffusion into co-cultures at concentrations sufficient to inhibit T-cell proliferation. MSCs contain measurable amounts of rapamycin after a 15-min exposure, and the potentiating effect is blocked by a neutralizing antibody to the drug. With the use of a pre-clinical model of acute graft-versus-host disease, we demonstrate that a low dose of rapamycin-treated but not untreated umbilical cord-derived MSCs significantly inhibit the onset of disease.CONCLUSIONS:
The use of treated MSCs may achieve clinical end points not reached with untreated MSCs and allow for infusion of fewer cells to reduce costs and minimize potential side effects.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Sirolimo
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Transplante de Células-Tronco Mesenquimais
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Doença Enxerto-Hospedeiro
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Tolerância Imunológica
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Imunossupressores
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article