Preconditioning of Rat Bone Marrow-Derived Mesenchymal Stromal Cells with Toll-Like Receptor Agonists
Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are dynamic cells that can sense the environment, adapting their regulatory functions to different conditions. Accordingly, the therapeutic potential of BM-MSCs can be modulated by preconditioning strategies aimed at modifying their paracrine a...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/7692973 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832545762546810880 |
|---|---|
| author | Fabiana Evaristo-Mendonça Gabriela Sardella-Silva Tais Hanae Kasai-Brunswick Raquel Maria Pereira Campos Pablo Domizi Marcelo Felippe Santiago Ricardo Augusto de Melo Reis Rosalia Mendez-Otero Victor Túlio Ribeiro-Resende Pedro Moreno Pimentel-Coelho |
| author_facet | Fabiana Evaristo-Mendonça Gabriela Sardella-Silva Tais Hanae Kasai-Brunswick Raquel Maria Pereira Campos Pablo Domizi Marcelo Felippe Santiago Ricardo Augusto de Melo Reis Rosalia Mendez-Otero Victor Túlio Ribeiro-Resende Pedro Moreno Pimentel-Coelho |
| author_sort | Fabiana Evaristo-Mendonça |
| collection | DOAJ |
| description | Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are dynamic cells that can sense the environment, adapting their regulatory functions to different conditions. Accordingly, the therapeutic potential of BM-MSCs can be modulated by preconditioning strategies aimed at modifying their paracrine action. Although rat BM-MSCs (rBM-MSCs) have been widely tested in preclinical research, most preconditioning studies have employed human and mouse BM-MSCs. Herein, we investigated whether rBM-MSCs modify their phenotype and paracrine functions in response to Toll-like receptor (TLR) agonists. The data showed that rBM-MSCs expressed TLR3, TLR4, and MDA5 mRNA and were able to internalize polyinosinic-polycytidylic acid (Poly(I:C)), a TLR3/MDA5 agonist. rBM-MSCs were then stimulated with Poly(I:C) or with lipopolysaccharide (LPS, a TLR4 agonist) for 1 h and were grown under normal culture conditions. LPS or Poly(I:C) stimulation did not affect the viability or the morphology of rBM-MSCs and did not modify the expression pattern of key cell surface markers. Poly(I:C) did not induce statistically significant changes in the release of several inflammatory mediators and VEGF by rBM-MSCs, although it tended to increase IL-6 and MCP-1 secretion, whereas LPS increased the release of IL-6, MCP-1, and VEGF, three factors that were constitutively secreted by unstimulated cells. The neurotrophic activity of the conditioned medium from unstimulated and LPS-preconditioned rBM-MSCs was investigated using dorsal root ganglion explants, showing that soluble factors produced by unstimulated and LPS-preconditioned rBM-MSCs can stimulate neurite outgrowth similarly, in a VEGF-dependent manner. LPS-preconditioned cells, however, were slightly more efficient in increasing the number of regrowing axons in a model of sciatic nerve transection in rats. In conclusion, LPS preconditioning boosted the production of constitutively secreted factors by rBM-MSCs, without changing their mesenchymal identity, an effect that requires further investigation in exploratory preclinical studies. |
| format | Article |
| id | doaj-art-1c89eb8b6eb746cd84f3a8bb0e07edee |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-1c89eb8b6eb746cd84f3a8bb0e07edee2025-02-03T07:24:43ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/76929737692973Preconditioning of Rat Bone Marrow-Derived Mesenchymal Stromal Cells with Toll-Like Receptor AgonistsFabiana Evaristo-Mendonça0Gabriela Sardella-Silva1Tais Hanae Kasai-Brunswick2Raquel Maria Pereira Campos3Pablo Domizi4Marcelo Felippe Santiago5Ricardo Augusto de Melo Reis6Rosalia Mendez-Otero7Victor Túlio Ribeiro-Resende8Pedro Moreno Pimentel-Coelho9Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilCentro Nacional de Biologia Estrutural e Bioimagem (CENABIO), Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilBone marrow-derived mesenchymal stromal cells (BM-MSCs) are dynamic cells that can sense the environment, adapting their regulatory functions to different conditions. Accordingly, the therapeutic potential of BM-MSCs can be modulated by preconditioning strategies aimed at modifying their paracrine action. Although rat BM-MSCs (rBM-MSCs) have been widely tested in preclinical research, most preconditioning studies have employed human and mouse BM-MSCs. Herein, we investigated whether rBM-MSCs modify their phenotype and paracrine functions in response to Toll-like receptor (TLR) agonists. The data showed that rBM-MSCs expressed TLR3, TLR4, and MDA5 mRNA and were able to internalize polyinosinic-polycytidylic acid (Poly(I:C)), a TLR3/MDA5 agonist. rBM-MSCs were then stimulated with Poly(I:C) or with lipopolysaccharide (LPS, a TLR4 agonist) for 1 h and were grown under normal culture conditions. LPS or Poly(I:C) stimulation did not affect the viability or the morphology of rBM-MSCs and did not modify the expression pattern of key cell surface markers. Poly(I:C) did not induce statistically significant changes in the release of several inflammatory mediators and VEGF by rBM-MSCs, although it tended to increase IL-6 and MCP-1 secretion, whereas LPS increased the release of IL-6, MCP-1, and VEGF, three factors that were constitutively secreted by unstimulated cells. The neurotrophic activity of the conditioned medium from unstimulated and LPS-preconditioned rBM-MSCs was investigated using dorsal root ganglion explants, showing that soluble factors produced by unstimulated and LPS-preconditioned rBM-MSCs can stimulate neurite outgrowth similarly, in a VEGF-dependent manner. LPS-preconditioned cells, however, were slightly more efficient in increasing the number of regrowing axons in a model of sciatic nerve transection in rats. In conclusion, LPS preconditioning boosted the production of constitutively secreted factors by rBM-MSCs, without changing their mesenchymal identity, an effect that requires further investigation in exploratory preclinical studies.http://dx.doi.org/10.1155/2019/7692973 |
| spellingShingle | Fabiana Evaristo-Mendonça Gabriela Sardella-Silva Tais Hanae Kasai-Brunswick Raquel Maria Pereira Campos Pablo Domizi Marcelo Felippe Santiago Ricardo Augusto de Melo Reis Rosalia Mendez-Otero Victor Túlio Ribeiro-Resende Pedro Moreno Pimentel-Coelho Preconditioning of Rat Bone Marrow-Derived Mesenchymal Stromal Cells with Toll-Like Receptor Agonists Stem Cells International |
| title | Preconditioning of Rat Bone Marrow-Derived Mesenchymal Stromal Cells with Toll-Like Receptor Agonists |
| title_full | Preconditioning of Rat Bone Marrow-Derived Mesenchymal Stromal Cells with Toll-Like Receptor Agonists |
| title_fullStr | Preconditioning of Rat Bone Marrow-Derived Mesenchymal Stromal Cells with Toll-Like Receptor Agonists |
| title_full_unstemmed | Preconditioning of Rat Bone Marrow-Derived Mesenchymal Stromal Cells with Toll-Like Receptor Agonists |
| title_short | Preconditioning of Rat Bone Marrow-Derived Mesenchymal Stromal Cells with Toll-Like Receptor Agonists |
| title_sort | preconditioning of rat bone marrow derived mesenchymal stromal cells with toll like receptor agonists |
| url | http://dx.doi.org/10.1155/2019/7692973 |
| work_keys_str_mv | AT fabianaevaristomendonca preconditioningofratbonemarrowderivedmesenchymalstromalcellswithtolllikereceptoragonists AT gabrielasardellasilva preconditioningofratbonemarrowderivedmesenchymalstromalcellswithtolllikereceptoragonists AT taishanaekasaibrunswick preconditioningofratbonemarrowderivedmesenchymalstromalcellswithtolllikereceptoragonists AT raquelmariapereiracampos preconditioningofratbonemarrowderivedmesenchymalstromalcellswithtolllikereceptoragonists AT pablodomizi preconditioningofratbonemarrowderivedmesenchymalstromalcellswithtolllikereceptoragonists AT marcelofelippesantiago preconditioningofratbonemarrowderivedmesenchymalstromalcellswithtolllikereceptoragonists AT ricardoaugustodemeloreis preconditioningofratbonemarrowderivedmesenchymalstromalcellswithtolllikereceptoragonists AT rosaliamendezotero preconditioningofratbonemarrowderivedmesenchymalstromalcellswithtolllikereceptoragonists AT victortulioribeiroresende preconditioningofratbonemarrowderivedmesenchymalstromalcellswithtolllikereceptoragonists AT pedromorenopimentelcoelho preconditioningofratbonemarrowderivedmesenchymalstromalcellswithtolllikereceptoragonists |