Effects of the post-spinal cord injury microenvironment on the differentiation capacity of human neural stem cells derived from induced pluripotent stem cells

C. López-Serrano, A. Torres-Espín, J. Hernández, A.B. Alvarez-Palomo, J. Requena, X. Gasull, Michael J. Edel, X. Navarro

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    © 2016 Cognizant, LLC.Spinal cord injury (SCI) causes loss of neural functions below the level of the lesion due to interruption of spinal pathways and secondary neurodegenerative processes. The transplant of neural stem cells (NSCs) is a promising approach for the repair of SCI. Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) is expected to provide an autologous source of iPSC-derived NSCs, avoiding the immune response as well as ethical issues. However, there is still limited information on the behavior and differentiation pattern of transplanted iPSC-derived NSCs within the damaged spinal cord. We transplanted iPSC-derived NSCs, obtained from adult human somatic cells, into rats at 0 or 7 days after SCI, and evaluated motor-evoked potentials and locomotion of the animals. We histologically analyzed engraftment, proliferation, and differentiation of the iPSC-derived NSCs and the spared tissue in the spinal cords at 7, 21, and 63 days posttransplant. Both transplanted groups showed a late decline in functional recovery compared to vehicle-injected groups. Histological analysis showed proliferation of transplanted cells within the tissue and that cells formed a mass. At the final time point, most grafted cells differentiated to neural and astroglial lineages, but not into oligodendrocytes, while some grafted cells remained undifferentiated and proliferative. The proinflammatory tissue microenviroment of the injured spinal cord induced proliferation of the grafted cells and, therefore, there are possible risks associated with iPSC-derived NSC transplantation. New approaches are needed to promote and guide cell differentiation, as well as reduce their tumorigenicity once the cells are transplanted at the lesion site.
    Original languageEnglish
    Pages (from-to)1833-1852
    Number of pages20
    JournalCell Transplantation
    Volume25
    Issue number10
    DOIs
    Publication statusPublished - 2016

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    Induced Pluripotent Stem Cells
    Neural Stem Cells
    Stem cells
    Spinal Cord Injuries
    Spinal Cord
    Cell Proliferation
    Motor Evoked Potentials
    Oligodendroglia
    Stem Cell Transplantation
    Locomotion
    Tissue
    Ethics
    Cell Differentiation
    Transplants
    Bioelectric potentials
    Rats
    Animals
    Repair

    Cite this

    López-Serrano, C., Torres-Espín, A., Hernández, J., Alvarez-Palomo, A. B., Requena, J., Gasull, X., ... Navarro, X. (2016). Effects of the post-spinal cord injury microenvironment on the differentiation capacity of human neural stem cells derived from induced pluripotent stem cells. Cell Transplantation, 25(10), 1833-1852. https://doi.org/10.3727/096368916X691312
    López-Serrano, C. ; Torres-Espín, A. ; Hernández, J. ; Alvarez-Palomo, A.B. ; Requena, J. ; Gasull, X. ; Edel, Michael J. ; Navarro, X. / Effects of the post-spinal cord injury microenvironment on the differentiation capacity of human neural stem cells derived from induced pluripotent stem cells. In: Cell Transplantation. 2016 ; Vol. 25, No. 10. pp. 1833-1852.
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    Effects of the post-spinal cord injury microenvironment on the differentiation capacity of human neural stem cells derived from induced pluripotent stem cells. / López-Serrano, C.; Torres-Espín, A.; Hernández, J.; Alvarez-Palomo, A.B.; Requena, J.; Gasull, X.; Edel, Michael J.; Navarro, X.

    In: Cell Transplantation, Vol. 25, No. 10, 2016, p. 1833-1852.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Effects of the post-spinal cord injury microenvironment on the differentiation capacity of human neural stem cells derived from induced pluripotent stem cells

    AU - López-Serrano, C.

    AU - Torres-Espín, A.

    AU - Hernández, J.

    AU - Alvarez-Palomo, A.B.

    AU - Requena, J.

    AU - Gasull, X.

    AU - Edel, Michael J.

    AU - Navarro, X.

    PY - 2016

    Y1 - 2016

    N2 - © 2016 Cognizant, LLC.Spinal cord injury (SCI) causes loss of neural functions below the level of the lesion due to interruption of spinal pathways and secondary neurodegenerative processes. The transplant of neural stem cells (NSCs) is a promising approach for the repair of SCI. Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) is expected to provide an autologous source of iPSC-derived NSCs, avoiding the immune response as well as ethical issues. However, there is still limited information on the behavior and differentiation pattern of transplanted iPSC-derived NSCs within the damaged spinal cord. We transplanted iPSC-derived NSCs, obtained from adult human somatic cells, into rats at 0 or 7 days after SCI, and evaluated motor-evoked potentials and locomotion of the animals. We histologically analyzed engraftment, proliferation, and differentiation of the iPSC-derived NSCs and the spared tissue in the spinal cords at 7, 21, and 63 days posttransplant. Both transplanted groups showed a late decline in functional recovery compared to vehicle-injected groups. Histological analysis showed proliferation of transplanted cells within the tissue and that cells formed a mass. At the final time point, most grafted cells differentiated to neural and astroglial lineages, but not into oligodendrocytes, while some grafted cells remained undifferentiated and proliferative. The proinflammatory tissue microenviroment of the injured spinal cord induced proliferation of the grafted cells and, therefore, there are possible risks associated with iPSC-derived NSC transplantation. New approaches are needed to promote and guide cell differentiation, as well as reduce their tumorigenicity once the cells are transplanted at the lesion site.

    AB - © 2016 Cognizant, LLC.Spinal cord injury (SCI) causes loss of neural functions below the level of the lesion due to interruption of spinal pathways and secondary neurodegenerative processes. The transplant of neural stem cells (NSCs) is a promising approach for the repair of SCI. Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) is expected to provide an autologous source of iPSC-derived NSCs, avoiding the immune response as well as ethical issues. However, there is still limited information on the behavior and differentiation pattern of transplanted iPSC-derived NSCs within the damaged spinal cord. We transplanted iPSC-derived NSCs, obtained from adult human somatic cells, into rats at 0 or 7 days after SCI, and evaluated motor-evoked potentials and locomotion of the animals. We histologically analyzed engraftment, proliferation, and differentiation of the iPSC-derived NSCs and the spared tissue in the spinal cords at 7, 21, and 63 days posttransplant. Both transplanted groups showed a late decline in functional recovery compared to vehicle-injected groups. Histological analysis showed proliferation of transplanted cells within the tissue and that cells formed a mass. At the final time point, most grafted cells differentiated to neural and astroglial lineages, but not into oligodendrocytes, while some grafted cells remained undifferentiated and proliferative. The proinflammatory tissue microenviroment of the injured spinal cord induced proliferation of the grafted cells and, therefore, there are possible risks associated with iPSC-derived NSC transplantation. New approaches are needed to promote and guide cell differentiation, as well as reduce their tumorigenicity once the cells are transplanted at the lesion site.

    U2 - 10.3727/096368916X691312

    DO - 10.3727/096368916X691312

    M3 - Article

    VL - 25

    SP - 1833

    EP - 1852

    JO - Cell Transplantation

    JF - Cell Transplantation

    SN - 0963-6897

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    ER -