Diabetic Ephrin-B2-Stimulated Peripheral Blood Mononuclear Cells Enhance Poststroke Recovery in Mice
Clinical trials of cell therapy in stroke favor autologous cell transplantation. To date, feasibility studies have used bone marrow-derived mononuclear cells, but harvesting bone marrow cells is invasive thus complicating bedside treatment. We investigated the therapeutic potential of peripheral blo...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2018/2431567 |
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| author | Rose Hilal Marine Poittevin Adrien Pasteur-Rousseau Adrien Cogo Gabrielle Mangin Marie Chevauché Yasmine Ziat José Vilar Jean-Marie Launay Jean-François Gautier Dong Broquères-You Bernard I. Levy Tatyana Merkulova-Rainon Nathalie Kubis |
| author_facet | Rose Hilal Marine Poittevin Adrien Pasteur-Rousseau Adrien Cogo Gabrielle Mangin Marie Chevauché Yasmine Ziat José Vilar Jean-Marie Launay Jean-François Gautier Dong Broquères-You Bernard I. Levy Tatyana Merkulova-Rainon Nathalie Kubis |
| author_sort | Rose Hilal |
| collection | DOAJ |
| description | Clinical trials of cell therapy in stroke favor autologous cell transplantation. To date, feasibility studies have used bone marrow-derived mononuclear cells, but harvesting bone marrow cells is invasive thus complicating bedside treatment. We investigated the therapeutic potential of peripheral blood-derived mononuclear cells (PB-MNC) harvested from diabetic patients and stimulated by ephrin-B2 (PB-MNC+) (500,000 cells), injected intravenously 18–24 hours after induced cerebral ischemia in mice. Infarct volume, neurological deficit, neurogenesis, angiogenesis, and inflammation were investigated as were the potential mechanisms of PB-MNC+ cells in poststroke neurorepair. At D3, infarct volume was reduced by 60% and 49% compared to unstimulated PB-MNC and PBS-treated mice, respectively. Compared to PBS, injection of PB-MNC+ increased cell proliferation in the peri-infarct area and the subventricular zone, decreased microglia/macrophage cell density, and upregulated TGF-β expression. At D14, microvessel density was decreased and functional recovery was enhanced compared to PBS-treated mice, whereas plasma levels of BDNF, a major regulator of neuroplasticity, were increased in mice treated with PB-MNC+ compared to the other two groups. Cell transcriptional analysis showed that ephrin-B2 induced phenotype switching of PB-MNC by upregulating genes controlling cell proliferation, inflammation, and angiogenesis, as confirmed by adhesion and Matrigel assays. Conclusions. This feasibility study suggests that PB-MNC+ transplantation poststroke could be a promising approach but warrants further investigation. If confirmed, this rapid, noninvasive bedside cell therapy strategy could be applied to stroke patients at the acute phase. |
| format | Article |
| id | doaj-art-c2140439f0a943aaa6225fd0519fdf73 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-c2140439f0a943aaa6225fd0519fdf732025-02-03T06:08:25ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/24315672431567Diabetic Ephrin-B2-Stimulated Peripheral Blood Mononuclear Cells Enhance Poststroke Recovery in MiceRose Hilal0Marine Poittevin1Adrien Pasteur-Rousseau2Adrien Cogo3Gabrielle Mangin4Marie Chevauché5Yasmine Ziat6José Vilar7Jean-Marie Launay8Jean-François Gautier9Dong Broquères-You10Bernard I. Levy11Tatyana Merkulova-Rainon12Nathalie Kubis13Sorbonne Paris Cité, CART, INSERM U965, Université Paris Diderot, 75475 Paris, FranceSorbonne Paris Cité, CART, INSERM U965, Université Paris Diderot, 75475 Paris, FranceSorbonne Paris Cité, CART, INSERM U965, Université Paris Diderot, 75475 Paris, FranceSorbonne Paris Cité, CART, INSERM U965, Université Paris Diderot, 75475 Paris, FranceSorbonne Paris Cité, CART, INSERM U965, Université Paris Diderot, 75475 Paris, FranceSorbonne Paris Cité, CART, INSERM U965, Université Paris Diderot, 75475 Paris, FranceSorbonne Paris Cité, CART, INSERM U965, Université Paris Diderot, 75475 Paris, FranceINSERM U970, Paris Cardiovascular Research Center, 75737 Paris, FranceService de Biochimie et Biologie Moléculaire, AP-HP, Hôpital Lariboisière, 75475 Paris, FranceCUDC, AP-HP, Hôpital Lariboisière, 75475 Paris, FranceInstitut Vaisseaux Sang, Hôpital Lariboisière, 75475 Paris, FranceInstitut Vaisseaux Sang, Hôpital Lariboisière, 75475 Paris, FranceSorbonne Paris Cité, CART, INSERM U965, Université Paris Diderot, 75475 Paris, FranceSorbonne Paris Cité, CART, INSERM U965, Université Paris Diderot, 75475 Paris, FranceClinical trials of cell therapy in stroke favor autologous cell transplantation. To date, feasibility studies have used bone marrow-derived mononuclear cells, but harvesting bone marrow cells is invasive thus complicating bedside treatment. We investigated the therapeutic potential of peripheral blood-derived mononuclear cells (PB-MNC) harvested from diabetic patients and stimulated by ephrin-B2 (PB-MNC+) (500,000 cells), injected intravenously 18–24 hours after induced cerebral ischemia in mice. Infarct volume, neurological deficit, neurogenesis, angiogenesis, and inflammation were investigated as were the potential mechanisms of PB-MNC+ cells in poststroke neurorepair. At D3, infarct volume was reduced by 60% and 49% compared to unstimulated PB-MNC and PBS-treated mice, respectively. Compared to PBS, injection of PB-MNC+ increased cell proliferation in the peri-infarct area and the subventricular zone, decreased microglia/macrophage cell density, and upregulated TGF-β expression. At D14, microvessel density was decreased and functional recovery was enhanced compared to PBS-treated mice, whereas plasma levels of BDNF, a major regulator of neuroplasticity, were increased in mice treated with PB-MNC+ compared to the other two groups. Cell transcriptional analysis showed that ephrin-B2 induced phenotype switching of PB-MNC by upregulating genes controlling cell proliferation, inflammation, and angiogenesis, as confirmed by adhesion and Matrigel assays. Conclusions. This feasibility study suggests that PB-MNC+ transplantation poststroke could be a promising approach but warrants further investigation. If confirmed, this rapid, noninvasive bedside cell therapy strategy could be applied to stroke patients at the acute phase.http://dx.doi.org/10.1155/2018/2431567 |
| spellingShingle | Rose Hilal Marine Poittevin Adrien Pasteur-Rousseau Adrien Cogo Gabrielle Mangin Marie Chevauché Yasmine Ziat José Vilar Jean-Marie Launay Jean-François Gautier Dong Broquères-You Bernard I. Levy Tatyana Merkulova-Rainon Nathalie Kubis Diabetic Ephrin-B2-Stimulated Peripheral Blood Mononuclear Cells Enhance Poststroke Recovery in Mice Stem Cells International |
| title | Diabetic Ephrin-B2-Stimulated Peripheral Blood Mononuclear Cells Enhance Poststroke Recovery in Mice |
| title_full | Diabetic Ephrin-B2-Stimulated Peripheral Blood Mononuclear Cells Enhance Poststroke Recovery in Mice |
| title_fullStr | Diabetic Ephrin-B2-Stimulated Peripheral Blood Mononuclear Cells Enhance Poststroke Recovery in Mice |
| title_full_unstemmed | Diabetic Ephrin-B2-Stimulated Peripheral Blood Mononuclear Cells Enhance Poststroke Recovery in Mice |
| title_short | Diabetic Ephrin-B2-Stimulated Peripheral Blood Mononuclear Cells Enhance Poststroke Recovery in Mice |
| title_sort | diabetic ephrin b2 stimulated peripheral blood mononuclear cells enhance poststroke recovery in mice |
| url | http://dx.doi.org/10.1155/2018/2431567 |
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