Protective effects of bone marrow stromal cell transplantation in injured rodent brain: Synthesis of neurotrophic factors

Qin Chen, Yan Long, Xiaoqing Yuan, LingLong Zou, Jiao Sun, Shengdi Chen, J. Regino Perez-Polo, Keyi Yang

    Research output: Contribution to journalArticle

    151 Citations (Scopus)

    Abstract

    Several groups have suggested that transplantation of marrow stromal cells (MSCs) promotes functional recovery in animal models of brain trauma. Recent studies indicate that tissue replacement by this method may not be the main source of therapeutic benefit, as transplanted MSCs have only limited ability to replace injured central nervous system (CNS) tissue. To gain insight into the mechanisms responsible for such effects, we systematically investigated the therapeutic potential of MSCs for treatment of brain injury. Using in vitro studies, we detected the synthesis of various growth factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and neurotrophin-3 (NT-3). Enzyme-linked immunosorbent assay (ELISA) demonstrated that MSCs cultured in Dulbecco's modified Eagle medium (DMEM) produced substantial amounts of NGF for at least 7 weeks, whereas the levels of BDNF, GDNF and NT-3 remained unchanged. In studies in mice, after intraventricular injection of MSCs, NGF levels were increased significantly in cerebrospinal fluid by ELISA, confirming our cell culture results. Further studies showed that treatment of traumatic brain injury with MSCs could attenuate the loss of cholinergic neuronal immunostaining in the medial septum of mice. These studies demonstrate for the first time that by increasing the brain concentration of NGF, intraventricularly transplanted MSCs might play an important role in the treatment of traumatic brain injury.

    Original languageEnglish (US)
    Pages (from-to)611-619
    Number of pages9
    JournalJournal of Neuroscience Research
    Volume80
    Issue number5
    DOIs
    StatePublished - Jun 1 2005

    Fingerprint

    Nerve Growth Factors
    Stromal Cells
    Bone Marrow Transplantation
    Mesenchymal Stromal Cells
    Rodentia
    Bone Marrow
    Nerve Growth Factor
    Brain
    Neurotrophin 3
    Glial Cell Line-Derived Neurotrophic Factor
    Brain-Derived Neurotrophic Factor
    Enzyme-Linked Immunosorbent Assay
    Intraventricular Injections
    Therapeutics
    Nerve Tissue
    Eagles
    Brain Injuries
    Cholinergic Agents
    Cerebrospinal Fluid
    Intercellular Signaling Peptides and Proteins

    Keywords

    • Marrow stromal cells
    • Nerve growth factor
    • Neurotrophic factor
    • Transplantation
    • Traumatic brain injury

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Protective effects of bone marrow stromal cell transplantation in injured rodent brain : Synthesis of neurotrophic factors. / Chen, Qin; Long, Yan; Yuan, Xiaoqing; Zou, LingLong; Sun, Jiao; Chen, Shengdi; Perez-Polo, J. Regino; Yang, Keyi.

    In: Journal of Neuroscience Research, Vol. 80, No. 5, 01.06.2005, p. 611-619.

    Research output: Contribution to journalArticle

    Chen, Qin ; Long, Yan ; Yuan, Xiaoqing ; Zou, LingLong ; Sun, Jiao ; Chen, Shengdi ; Perez-Polo, J. Regino ; Yang, Keyi. / Protective effects of bone marrow stromal cell transplantation in injured rodent brain : Synthesis of neurotrophic factors. In: Journal of Neuroscience Research. 2005 ; Vol. 80, No. 5. pp. 611-619.
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    abstract = "Several groups have suggested that transplantation of marrow stromal cells (MSCs) promotes functional recovery in animal models of brain trauma. Recent studies indicate that tissue replacement by this method may not be the main source of therapeutic benefit, as transplanted MSCs have only limited ability to replace injured central nervous system (CNS) tissue. To gain insight into the mechanisms responsible for such effects, we systematically investigated the therapeutic potential of MSCs for treatment of brain injury. Using in vitro studies, we detected the synthesis of various growth factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and neurotrophin-3 (NT-3). Enzyme-linked immunosorbent assay (ELISA) demonstrated that MSCs cultured in Dulbecco's modified Eagle medium (DMEM) produced substantial amounts of NGF for at least 7 weeks, whereas the levels of BDNF, GDNF and NT-3 remained unchanged. In studies in mice, after intraventricular injection of MSCs, NGF levels were increased significantly in cerebrospinal fluid by ELISA, confirming our cell culture results. Further studies showed that treatment of traumatic brain injury with MSCs could attenuate the loss of cholinergic neuronal immunostaining in the medial septum of mice. These studies demonstrate for the first time that by increasing the brain concentration of NGF, intraventricularly transplanted MSCs might play an important role in the treatment of traumatic brain injury.",
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