Neuroprotection and Axonal Regeneration Induced by Bone Marrow Mesenchymal Stromal Cells Depend on the Type of Transplant

Mesenchymal stromal cell (MSC) therapy to treat neurodegenerative diseases has not been as successful as expected in some preclinical studies. Because preclinical research is so diverse, it is difficult to know whether the therapeutic outcome is due to the cell type, the type of transplant or the mo...

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Autores principales:	María Norte-Muñoz, Fernando Lucas-Ruiz, Alejandro Gallego-Ortega, David García-Bernal, Francisco J. Valiente-Soriano, Pedro de la Villa, Manuel Vidal-Sanz, Marta Agudo-Barriuso
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	retinal ganglion cell optic nerve crush bone marrow mesenchymal stromal cells syngraft allograft xenograft Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a1cc733633bd452d888e2d1bf5ec83b6
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spelling	oai:doaj.org-article:a1cc733633bd452d888e2d1bf5ec83b62021-11-04T07:10:52ZNeuroprotection and Axonal Regeneration Induced by Bone Marrow Mesenchymal Stromal Cells Depend on the Type of Transplant2296-634X10.3389/fcell.2021.772223https://doaj.org/article/a1cc733633bd452d888e2d1bf5ec83b62021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.772223/fullhttps://doaj.org/toc/2296-634XMesenchymal stromal cell (MSC) therapy to treat neurodegenerative diseases has not been as successful as expected in some preclinical studies. Because preclinical research is so diverse, it is difficult to know whether the therapeutic outcome is due to the cell type, the type of transplant or the model of disease. Our aim here was to analyze the effect of the type of transplant on neuroprotection and axonal regeneration, so we tested MSCs from the same niche in the same model of neurodegeneration in the three transplantation settings: xenogeneic, syngeneic and allogeneic. For this, bone marrow mesenchymal stromal cells (BM-MSCs) isolated from healthy human volunteers or C57/BL6 mice were injected into the vitreous body of C57/BL6 mice (xenograft and syngraft) or BALB/c mice (allograft) right after optic nerve axotomy. As controls, vehicle matched groups were done. Retinal anatomy and function were analyzed in vivo by optical coherence tomography and electroretinogram, respectively. Survival of vision forming (Brn3a+) and non-vision forming (melanopsin+) retinal ganglion cells (RGCs) was assessed at 3, 5 and 90 days after the lesion. Regenerative axons were visualized by cholera toxin β anterograde transport. Our data show that grafted BM-MSCs did not integrate in the retina but formed a mesh on top of the ganglion cell layer. The xenotransplant caused retinal edema, detachment and folding, and a significant decrease of functionality compared to the murine transplants. RGC survival and axonal regeneration were significantly higher in the syngrafted retinas than in the other two groups or vehicle controls. Melanopsin+RGCs, but not Brn3a+RGCs, were also neuroprotected by the xenograft. In conclusion, the type of transplant has an impact on the therapeutic effect of BM-MSCs affecting not only neuronal survival but also the host tissue response. Our data indicate that syngrafts may be more beneficial than allografts and, interestingly, that the type of neuron that is rescued also plays a significant role in the successfulness of the cell therapy.María Norte-MuñozFernando Lucas-RuizAlejandro Gallego-OrtegaDavid García-BernalFrancisco J. Valiente-SorianoPedro de la VillaManuel Vidal-SanzMarta Agudo-BarriusoFrontiers Media S.A.articleretinal ganglion celloptic nerve crushbone marrow mesenchymal stromal cellssyngraftallograftxenograftBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	retinal ganglion cell optic nerve crush bone marrow mesenchymal stromal cells syngraft allograft xenograft Biology (General) QH301-705.5
spellingShingle	retinal ganglion cell optic nerve crush bone marrow mesenchymal stromal cells syngraft allograft xenograft Biology (General) QH301-705.5 María Norte-Muñoz Fernando Lucas-Ruiz Alejandro Gallego-Ortega David García-Bernal Francisco J. Valiente-Soriano Pedro de la Villa Manuel Vidal-Sanz Marta Agudo-Barriuso Neuroprotection and Axonal Regeneration Induced by Bone Marrow Mesenchymal Stromal Cells Depend on the Type of Transplant
description	Mesenchymal stromal cell (MSC) therapy to treat neurodegenerative diseases has not been as successful as expected in some preclinical studies. Because preclinical research is so diverse, it is difficult to know whether the therapeutic outcome is due to the cell type, the type of transplant or the model of disease. Our aim here was to analyze the effect of the type of transplant on neuroprotection and axonal regeneration, so we tested MSCs from the same niche in the same model of neurodegeneration in the three transplantation settings: xenogeneic, syngeneic and allogeneic. For this, bone marrow mesenchymal stromal cells (BM-MSCs) isolated from healthy human volunteers or C57/BL6 mice were injected into the vitreous body of C57/BL6 mice (xenograft and syngraft) or BALB/c mice (allograft) right after optic nerve axotomy. As controls, vehicle matched groups were done. Retinal anatomy and function were analyzed in vivo by optical coherence tomography and electroretinogram, respectively. Survival of vision forming (Brn3a+) and non-vision forming (melanopsin+) retinal ganglion cells (RGCs) was assessed at 3, 5 and 90 days after the lesion. Regenerative axons were visualized by cholera toxin β anterograde transport. Our data show that grafted BM-MSCs did not integrate in the retina but formed a mesh on top of the ganglion cell layer. The xenotransplant caused retinal edema, detachment and folding, and a significant decrease of functionality compared to the murine transplants. RGC survival and axonal regeneration were significantly higher in the syngrafted retinas than in the other two groups or vehicle controls. Melanopsin+RGCs, but not Brn3a+RGCs, were also neuroprotected by the xenograft. In conclusion, the type of transplant has an impact on the therapeutic effect of BM-MSCs affecting not only neuronal survival but also the host tissue response. Our data indicate that syngrafts may be more beneficial than allografts and, interestingly, that the type of neuron that is rescued also plays a significant role in the successfulness of the cell therapy.
format	article
author	María Norte-Muñoz Fernando Lucas-Ruiz Alejandro Gallego-Ortega David García-Bernal Francisco J. Valiente-Soriano Pedro de la Villa Manuel Vidal-Sanz Marta Agudo-Barriuso
author_facet	María Norte-Muñoz Fernando Lucas-Ruiz Alejandro Gallego-Ortega David García-Bernal Francisco J. Valiente-Soriano Pedro de la Villa Manuel Vidal-Sanz Marta Agudo-Barriuso
author_sort	María Norte-Muñoz
title	Neuroprotection and Axonal Regeneration Induced by Bone Marrow Mesenchymal Stromal Cells Depend on the Type of Transplant
title_short	Neuroprotection and Axonal Regeneration Induced by Bone Marrow Mesenchymal Stromal Cells Depend on the Type of Transplant
title_full	Neuroprotection and Axonal Regeneration Induced by Bone Marrow Mesenchymal Stromal Cells Depend on the Type of Transplant
title_fullStr	Neuroprotection and Axonal Regeneration Induced by Bone Marrow Mesenchymal Stromal Cells Depend on the Type of Transplant
title_full_unstemmed	Neuroprotection and Axonal Regeneration Induced by Bone Marrow Mesenchymal Stromal Cells Depend on the Type of Transplant
title_sort	neuroprotection and axonal regeneration induced by bone marrow mesenchymal stromal cells depend on the type of transplant
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/a1cc733633bd452d888e2d1bf5ec83b6
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Neuroprotection and Axonal Regeneration Induced by Bone Marrow Mesenchymal Stromal Cells Depend on the Type of Transplant

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