Umbilical cord blood mononuclear cell transplantation for neonatal hypoxic–ischemic encephalopathy

Pimentel‐Coelho, Pedro M.; Rosado-de-Castro, Paulo Henrique; Fonseca, Leila S.; Mendez-Otero, Rosália

doi:10.1038/pr.2011.59

Cited by 70 publications

(54 citation statements)

References 113 publications

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“…hUCB stem cells have also been used experimentally in animal models of TBI. In some studies, transplanted cells derived from the mononuclear fraction of hUCB conferred neuroprotection by decreasing inflammation and brain tissue loss, promoting neurogenesis, and rescue of neurological dysfunctions (e.g., 11,41,78). Additionally, mesenchymal stem cells (MSCs) derived from hUCB promoted functional benefits by increasing angiogenesis and vasculogenesis (1,53,55).…”

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), 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%

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

et al. 2015

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“…In addition, we can avoid intracranial injections since they can be administered systematically through intravenous, intraperitoneal, or even intranasal routes [10] . For instance, human umbilical cord blood cells (hUCBCs) can be obtained at birth and transplanted as an autologous source [15] . Recently, our group provided evidence for the benefit of hUCBCs in a neonatal rat model [16,17] , and clinical trials are currently under way (ClinicalTrials.gov: NCT02256618).…”

Section: Introductionmentioning

confidence: 99%

Dedifferentiated Fat Cells as a Novel Source for Cell Therapy to Target Neonatal Hypoxic-Ischemic Encephalopathy

Mikrogeorgiou¹,

Sato²,

Kondo³

et al. 2017

Dev Neurosci

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Neonatal hypoxic-ischemic (HI) encephalopathy (HIE) remains a major cause of mortality and persistent neurological disabilities in affected individuals. At present, hypothermia is considered to be the only applicable treatment option, although growing evidence suggests that cell-based therapy might achieve better outcomes. Dedifferentiated fat (DFAT) cells are derived from mature adipocytes via a dedifferentiation strategy called ceiling culture. Their abundance and ready availability might make them an ideal therapeutic tool for the treatment of HIE. In the present study, we aimed to determine whether the outcome of HIE can be improved by DFAT cell treatment. HI injury was achieved by ligating the left common carotid artery in 7-day-old rat pups, followed by 1-h exposure to 8% O₂. Subsequently, the severity of damage was assessed by diffusion-weighted magnetic resonance imaging to assign animals to equivalent groups. 24 h after hypoxia, DFAT cells were injected at 10⁵ cells/pup into the right external jugular vein. To evaluate brain damage in the acute phase, a group of animals was sacrificed 48 h after the insult, and paraffin sections of the brain were stained to assess several acute injury markers. In the chronic phase, the behavioral outcome was measured by performing a series of behavioral tests. From the 24th day of age, the sensorimotor function was examined by evaluating the initial forepaw placement on a cylinder wall and the latency to falling from a rotarod treadmill. The cognitive function was tested with the novel object recognition (NOR) test. In vitro conditioned medium (CM) prepared from cultured DFAT cells was added at various concentrations to neuronal cell cultures, which were then exposed to oxygen-glucose deprivation (OGD). The number of cells that stained positive for the apoptosis marker active caspase-3 decreased by 73 and 52% in the hippocampus and temporal cortex areas of the brain, respectively, in the DFAT-treated pups. Similarly, the numbers of ED-1-positive cells (activated microglia) decreased by 66 and 44%, respectively, in the same areas in the DFAT-treated group. The number of cells positive for the oxidative stress marker 4-hydroxyl-2-nonenal decreased by 68 and 50% in the hippocampus and the parietal cortex areas, respectively, in the DFAT-treated group. The HI insult led to a motor deficit according to the rotarod treadmill and cylinder test, where it significantly affected the vehicle group, whereas no difference was confirmed between the DFAT and sham groups. However, the NOR test indicated no significant differences between any of the groups. DFAT treatment did not reduce the infarct volume, which was confirmed immunohistochemically. According to in vitro experiments, the cell death rates in the DFAT-CM-treated cells were significantly lower than those in the controls when DFAT-CM was added 48 h prior to OGD. The treatment effect of adding DFAT-CM 24 h prior to OGD was also significant. Our results indicate that intravenous injection with DFAT cells i...

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“…Most of the studies in animal models of stroke have transplanted the whole mononuclear cell (MNC) fraction from one of these sources, which also contains other cell types, including monocytes and lymphocytes, in addition to HSPC, MSC, and endothelial progenitor cells [31].…”

Section: Non-nspcmentioning

confidence: 99%

The Rise of Cell Therapy Trials for Stroke: Review of Published and Registered Studies

Rosado-de-Castro

Pimentel‐Coelho

Fonseca

et al. 2013

Stem Cells and Development

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Stroke is the second leading cause of death and the third leading cause of disability worldwide. Approximately 16 million first-ever strokes occur each year, leading to nearly 6 million deaths. Nevertheless, currently, very few therapeutic options are available. Cell therapies have been applied successfully in different hematological diseases, and are currently being investigated for treating ischemic heart disease, with promising results. Recent preclinical studies have indicated that cell therapies may provide structural and functional benefits after stroke. However, the effects of these treatments are not yet fully understood and are the subject of continuing investigation. Meanwhile, different clinical trials for stroke, the majority of them small, nonrandomized, and uncontrolled, have been reported, and their results indicate that cell therapy seems safe and feasible in these conditions. In the last 2 years, the number of published and registered trials has dramatically increased. Here, we review the main findings available in the field, with emphasis on the clinical results. Moreover, we address some of the questions that have been raised to date, to improve future studies.

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Umbilical cord blood mononuclear cell transplantation for neonatal hypoxic–ischemic encephalopathy

Cited by 70 publications

References 113 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

Dedifferentiated Fat Cells as a Novel Source for Cell Therapy to Target Neonatal Hypoxic-Ischemic Encephalopathy

The Rise of Cell Therapy Trials for Stroke: Review of Published and Registered Studies

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