Intravenous Transplants of Human Adipose-Derived Stem Cell Protect the Brain from Traumatic Brain Injury-Induced Neurodegeneration and Motor and Cognitive Impairments: Cell Graft Biodistribution and Soluble Factors in Young and Aged Rats

Tajiri, Naoki; Acosta, Sandra; Shahaduzzaman, M.; Ishikawa, Hiroto; Shinozuka, Kazutaka; Pabon, Mibel; Hernandez-Ontiveros, Diana G.; Kim, D. W.; Metcalf, Christopher; Staples, Meaghan; Dailey, Travis; Vasconcellos, J.; Franyuti, Giorgio; Gould, Lisa; Patel, Niketa A.; Cooper, Denise R.; Kaneko, Yuji; Borlongan, Cesar V.; Bickford, Paula C.

doi:10.1523/jneurosci.2425-13.2014

Cited by 142 publications

(132 citation statements)

References 67 publications

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“…Considering the massive secondary cell death mediating the progression of TBI, novel treatments have been fashioned to target the delayed therapeutic time window post-TBI referred to as "neuroregeneration" in contrast to the narrow "neuroprotection" window relegated to the acute TBI phase (71,109). A major component of regenerative medicine is stem cell-based therapeutics, which have shown promising therapeutic potential for various types of neurological disorders, including TBI (e.g., 57,58,62,109,130), and have reached limited clinical trials [for review see (43)].…”

Section: Stem Cell Transplantation In Tbimentioning

confidence: 99%

“…A major component of regenerative medicine is stem cell-based therapeutics, which have shown promising therapeutic potential for various types of neurological disorders, including TBI (e.g., 57,58,62,109,130), and have reached limited clinical trials [for review see (43)]. Translating cell therapy for treatment of brain diseases to the clinic has involved testing the safety, efficacy, and mechanisms of action of a variety of transplantable donor cells, including fetal stem cells, cancer-derived neuron-like cells, embryonic stem cells, induced pluripotent stem cells, and adult stem cells, such as umbilical cord blood, bone marrow stromal cells, amnion cells, among others (16,57,58,62,63,74,75,84,87,90,109,130). However, among these various types of stem cells, adult stem cells are of interest, as they circumvent ethical and moral problems and also teratogenic and oncogenic risks usually associated with transplantation of embryonal or fetal-derived stem cells (85).…”

Section: Stem Cell Transplantation In Tbimentioning

confidence: 99%

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G-CSF as an Adjunctive Therapy with Umbilical Cord Blood Cell Transplantation for Traumatic Brain Injury

et al. 2015

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Traumatic brain injury (TBI), a major contributor to deaths and permanent disability worldwide, has been recently described as a progressive cell death process rather than an acute event. TBI pathophysiology is complicated and can be distinguished by the initial primary injury and the subsequent secondary injury that ensues days after the trauma. Therapeutic opportunities for TBI remain very limited with patients subjected to surgery or rehabilitation therapy. The efficacy of stem cell-based interventions, as well as neuroprotective agents in other neurological disorders of which pathologies overlap with TBI, indicates their potential as alternative TBI treatments. Furthermore, their therapeutic limitations may be augmented when combination therapy is pursued instead of using a single agent. Indeed, we demonstrated remarkable combined efficacy of human umbilical cord blood (hUCB) cell therapy and granulocyte-colony-stimulating factor (G-CSF) treatment in TBI models, providing essential evidence for the translation of this approach to treat TBI. Further studies are warranted to determine the mechanisms underlying therapeutic benefits exerted by hUCB + G-CSF in order to enhance its safety and efficacy in the clinic.

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Section: Stem Cell Transplantation In Tbimentioning

confidence: 99%

Section: Stem Cell Transplantation In Tbimentioning

confidence: 99%

G-CSF as an Adjunctive Therapy with Umbilical Cord Blood Cell Transplantation for Traumatic Brain Injury

et al. 2015

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“…Traumatic brain injury (TBI) is an acute intracranial injury caused by a sudden external force that may lead to brain concussion, contusion/laceration, bleeding, neurological dysfunction, and even death [1]. The prognosis and outcome of TBI is closely associated with the occurrence and existence of extracranial complications besides neurotrauma [2].…”

Section: Introductionmentioning

confidence: 99%

Acute Traumatic Brain Injury Induces CD4<sup>+</sup> and CD8<sup>+</sup> T Cell Functional Impairment by Upregulating the Expression of PD-1 via the Activated Sympathetic Nervous System

Yang

Chen

et al. 2019

Neuroimmunomodulation

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Objective: Traumatic brain injury (TBI) induces immunosuppression in the acute phase, and the activation of the sympathetic nervous system (SNS) might play a role in this process, but the mechanism involved is unknown. Herein, we explored the impact of acute (a)TBI on the peripheral immune system and its correlation with the SNS and the T cell exhaustion marker, PD-1 (programmed cell death-1). Methods: Flow cytometry (FCM) was performed to analyze the expression of T cell markers and intracellular cytokines, interferon-γ and tumor necrosis factor-α, and the T cell exhaustion marker, PD-1, in the peripheral blood mononuclear cells (PBMCs) of TBI rats. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the concentration of norepinephrine (NE) in the serum. Propranolol was administrated to block the SNS in vivo and NE stimulation was used to imitate the activation of the SNS in vitro. Results: We found that the concentration of NE was significantly elevated after TBI, and the dysfunction of CD4⁺ and CD8⁺ T cells was reversed by the SNS blocker propranolol in vivo and imitated by the SNS neurotransmitter NE in vitro. The expression of PD-1 on CD4⁺ and CD8⁺ T cells was upregulated after aTBI, which was reversed by propranolol administration in vivo and imitated by NE stimulation in vitro. Furthermore, the PD-1 blocker reversed the dysfunction of CD4⁺ and CD8⁺T cells in vitro. Conclusion: Our findings demonstrated that aTBI activated the SNS, and further upregulated the expression of PD-1 on CD4⁺ and CD8⁺ T cells, which, in turn, impaired their function and contributed to immunosuppression.

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“…Multiple sclerosis (MS), also known as disseminated sclerosis or encephalomyelitis disseminate, is an inflammatory disease (48). Previous studies have demonstrated the potential of stem cell-based MS therapy in autoimmune and cuprizone models of MS (49 -51).…”

Section: Multiple Sclerosismentioning

confidence: 99%

Therapeutic Potential of Human Adipose-Derived Stem Cells in Neurological Disorders

2014

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Abstract. Stem cell therapy has been noted as a novel strategy to various diseases including neurological disorders such as Alzheimer's disease, Parkinson's disease, stroke, amyotrophic lateral sclerosis, and Huntington's disease that have no effective treatment available to date. The adipose-derived stem cells (ASCs), mesenchymal stem cells (MSCs) isolated from adipose tissue, are well known for their pluripotency with the ability to differentiate into various types of cells and immuno-modulatory property. These biological features make ASCs a promising source for regenerative cell therapy in neurological disorders. Here we discuss the recent progress of regenerative therapies in various neurological disorders utilizing ASCs.

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Intravenous Transplants of Human Adipose-Derived Stem Cell Protect the Brain from Traumatic Brain Injury-Induced Neurodegeneration and Motor and Cognitive Impairments: Cell Graft Biodistribution and Soluble Factors in Young and Aged Rats

Cited by 142 publications

References 67 publications

G-CSF as an Adjunctive Therapy with Umbilical Cord Blood Cell Transplantation for Traumatic Brain Injury

G-CSF as an Adjunctive Therapy with Umbilical Cord Blood Cell Transplantation for Traumatic Brain Injury

Acute Traumatic Brain Injury Induces CD4<sup>+</sup> and CD8<sup>+</sup> T Cell Functional Impairment by Upregulating the Expression of PD-1 via the Activated Sympathetic Nervous System

Therapeutic Potential of Human Adipose-Derived Stem Cells in Neurological Disorders

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