Infusion of Human Umbilical Cord Blood Cells Ameliorates Hind Limb Dysfunction in Experimental Spinal Cord Injury through Anti-inflammatory, Vasculogenic and Neurotrophic Mechanisms

Chen, Chun-Ta; Foo, Ning-Hui; Liu, Won-Shiung; Chen, Sheng-Hsien

doi:10.1016/s1875-9572(08)60017-0

Cited by 42 publications

(36 citation statements)

References 29 publications

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“…18 In addition, neurological disorders such as trauma, stroke and neurodegenerative diseases may represent another target for cell-based regenerative medicine using HUCB-derived cells. The therapeutic potential of whole HUCB and derived mononuclear cells (MNCs) in neurological disorders was investigated in animal models of central nervous system damage induced by hemorrhagic brain injury, 19 heatstroke, 20 middle cerebral artery occlusion stroke model, 21 spinal cord injury, 22 as well as TBI. 23 Given the fact that mesenchymal stem cells (MSCs) are frequently used for cell therapy of neurodegenerative disorders in clinical trials, 8,24 a recent study demonstrated the efficacy of HUCBderived MSCs in protecting mice brains after trauma.…”

Section: Introductionmentioning

confidence: 99%

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Arien‐Zakay

Gincberg

Nagler³

et al. 2014

Journal of Neurotrauma

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Treatment of traumatic brain injury (TBI) is still an unmet need. Cell therapy by human umbilical cord blood (HUCB) has shown promising results in animal models of TBI and is under evaluation in clinical trials. HUCB contains different cell populations but to date, only mesenchymal stem cells have been evaluated for therapy of TBI. Here we present the neurotherapeutic effect, as evaluated by neurological score, using a single dose of HUCB-derived mononuclear cells (MNCs) upon intravenous (IV) administration one day post-trauma in a mouse model of closed head injury (CHI). Delayed (eight days post-trauma) intracerebroventricular administration of MNCs showed improved neurobehavioral deficits thereby extending the therapeutic window for treating TBI. Further, we demonstrated for the first time that HUCBderived pan-hematopoietic CD45 positive (CD45 + ) cells, isolated by magnetic sorting and characterized by expression of CD45 and CD11b markers (96-99%), improved the neurobehavioral deficits upon IV administration, which persisted for 35 days. The therapeutic effect was in a direct correlation to a reduction in the lesion volume and decreased by pre-treatment of the cells with anti-human-CD45 antibody. At the site of brain injury, 1.5-2 h after transplantation, HUCBderived cells were identified by near infrared scanning and immunohistochemistry using anti-human-CD45 and antihuman-nuclei antibodies. Nerve growth factor and vascular endothelial growth factor levels were differentially expressed in both ipsilateral and contralateral brain hemispheres, thirty-five days after CHI, measured by enzyme-linked immunosorbent assay. These findings indicate the neurotherapeutic potential of HUCB-derived CD45+ cell population in a mouse model of TBI and propose their use in the clinical setting of human TBI.

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Section: Introductionmentioning

confidence: 99%

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Arien‐Zakay

Gincberg

Nagler³

et al. 2014

Journal of Neurotrauma

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“…Kao et al [78] , suggested that hUCB derived-CD34 + cells can induce angiogenesis and endo/exogenous neurogenesis in SCI. In addition, Chen et al [79] recently showed that hUCB stem cells have the ability to secrete multiple neurotrophic factors. Their study demonstrated an elevation of neuroprotective cytokine serum IL-10 levels and a decrease in TNF-α levels after hUCB stem cells infusion.…”

Section: Human Umbilical Cord Blood-derived Mscsmentioning

confidence: 99%

Mesenchymal stem cells in the treatment of spinal cord injuries: A review

Dasari

Veeravalli

Dinh

2014

WJSC

182

144

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With technological advances in basic research, the intricate mechanism of secondary delayed spinal cord injury (SCI) continues to unravel at a rapid pace. However, despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord, the cure for paralysis remains elusive. Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI. R ecent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results. An array of mesenchymal stem cells (MSCs) from various sources with novel and promising strategies are being developed to improve function after SCI. In this review, we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI. We will discuss the progress of MSCs application in research, focusing on the neuroprotective properties of MSCs. Finally, we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI. Core tip: Despite our deeper understanding of the molecular changes that occurs after the spinal cord injury (SCI), the cure for paralysis remains elusive. In this review, the pathophysiology of SCI and characteristics and potential sources of mesenchymal stem cells (MSCs) that can be used in the treatment of SCI were discussed. We also discussed the progress of application of MSCs in research focusing on the neuroprotective properties of MSCs. Finally, we discussed the results from preclinical and clinical trials involving stem cell-based therapy in SCI.

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“…показали, [61]. Неврологическое улучше-ние при трансплантации МНК пуповинной кро-ви продемонстрировано также в моделях трав-мы головного и спинного мозга [7,44], детского церебрального паралича (ДЦП) [53], болезни Альцгеймера [14] и бокового амиотрофического склероза [19]. Клиническая апробация клеток пуповинной крови показала безопасность и эффективность в лечении гипоксически-ишемической энцефа-лопатии новорожденных [13], ДЦП [31,56] и ау-тизма [47].…”

Section: Chernykh Er Et Al черных ер и др Medical Immunology (Runclassified

The Role of Macrophages in Damage Recovery of Central Nervous System: New Options for Treatment of Neurological Disorders

Рэмовна¹,

Shevela²,

Ostanin³

2017

Med. immunol.

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Адрес для переписки:Черных Елена Рэмовна ФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии» 630099, Россия, г. Новосибирск, ул. Ядринцевская, 14. Тел.: 8 (383) 236-03-29. Факс: 8 (383) 222-70-28. Е-mail: ct_lab@mail.ru Address for correspondence:Chernykh Elena R. Research Institute of Fundamental and Clinical Immunology 630099, Russian Federation, Novosibirsk, » // Медицинская иммунология, 2017. Т. 19, № 1. С. 7-18. doi: 10.15789/1563-0625-2017-1-7-18 © Черных Е.Р. и соавт., 2017 /Meditsinskaya Immunologiya, 2017, Vol. 19, no. 1, pp. 7-18. doi: 10.15789/1563-0625-2017 Резюме. Смена существующих парадигм относительно регенеративного потенциала центральной нервной системы (ЦНС) и роли иммунных клеток в процессах восстановления поврежденной нерв-ной ткани открывают новые перспективы лечения неврологических расстройств на основе иммуно-терапевтических подходов. Настоящий обзор посвящен анализу роли макрофагов в восстановлении повреждений в ЦНС и включает данные о функциональной гетерогенности клеток микроглии и ма-крофагов моноцитарного происхождения, путях рекрутирования моноцитов в ЦНС, взаимоотноше-нии клеток микроглии и рекрутируемых макрофагов и балансе М1/М2-клеток при нейропатологии. Кроме того, в обзоре приводится экспериментальное обоснование участия макрофагов в восстанов-лении повреждений ЦНС и рассматриваются механизмы регенеративной активности макрофагов. Приведенные данные позволяют рассматривать макрофаги в качестве новой мишени терапевти-ческих воздействий для подавления нейровоспалительной реакции и усиления репаративных про-цессов. Первые шаги в этой области свидетельствуют о перспективности применения моноцитов/ макрофагов или технологий М1→М2 переключения в лечении неврологических расстройств и обо-сновывают необходимость дальнейших исследований в данном направлении. Ключевые слова: ЦНС, макрофаги, микроглия, макрофаги моноцитарного происхождения, функциональные фенотипы, нейропротекция, нейрорегенерация, ангиогенез, ДЦП, инсульт, регенеративная иммунотерапия THE ROLE OF MACROPHAGES IN DAMAGE RECOVERY OF CENTRAL NERVOUS SYSTEM: NEW OPTIONS FOR TREATMENT OF NEUROLOGICAL DISORDERSChernykh E.R., Shevela E.Ya., Ostanin A.A. Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian FederationAbstract. Evolution of existing paradigms on regenerative capacity of the central nervous system (CNS) and eventual role of immune cells in restoration of damaged nervous tissue offers new prospectives in treatment 8 Chernykh E. R. et al. Черных Е.Р. и др. Medical Immunology (Russia)/Meditsinskaya Immunologiya Медицинская Иммунология of neurological disorders based on immunotherapeutic approaches. Present review article addresses a role of macrophages in restoration of damaged CNS and provides data on functional heterogeneity of resident tissue macrophages (microglia), and monocyte-derived macrophages. We discuss possible ways of monocyte recruitment to CNS, relationships between microglia and recruited macrophages, as well as M1/M2 ...

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Infusion of Human Umbilical Cord Blood Cells Ameliorates Hind Limb Dysfunction in Experimental Spinal Cord Injury through Anti-inflammatory, Vasculogenic and Neurotrophic Mechanisms

Abstract: Our results demonstrate that HUCBC therapy may be beneficial for the recovery of SCI-induced hind limb dysfunction by increasing serum levels of IL-10, VEGF and GDNF in SCI rats.

Cited by 42 publications

References 29 publications

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Mesenchymal stem cells in the treatment of spinal cord injuries: A review

The Role of Macrophages in Damage Recovery of Central Nervous System: New Options for Treatment of Neurological Disorders

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Infusion of Human Umbilical Cord Blood Cells Ameliorates Hind Limb Dysfunction in Experimental Spinal Cord Injury through Anti-inflammatory, Vasculogenic and Neurotrophic Mechanisms

Abstract: Our results demonstrate that HUCBC therapy may be beneficial for the recovery of SCI-induced hind limb dysfunction by increasing serum levels of IL-10, VEGF and GDNF in SCI rats.

Cited by 42 publications

References 29 publications

Neurotherapeutic Effect of Cord Blood Derived CD45+Hematopoietic Cells in Mice after Traumatic Brain Injury

Neurotherapeutic Effect of Cord Blood Derived CD45+Hematopoietic Cells in Mice after Traumatic Brain Injury

Mesenchymal stem cells in the treatment of spinal cord injuries: A review

The Role of Macrophages in Damage Recovery of Central Nervous System: New Options for Treatment of Neurological Disorders

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Product

Resources

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Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury