Umbilical Cord Blood‐Derived Aldehyde Dehydrogenase‐Expressing Progenitor Cells Promote Recovery from Acute Ischemic Injury

Putman, David M.; Liu, Kevin Y.; Broughton, Heather C.; Bell, Gillian I.; Hess, David A.

doi:10.1002/stem.1206

Cited by 49 publications

(73 citation statements)

References 53 publications

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“…As reported by Hess et al, ALDH high HSPCs from TCB demonstrated reliable NOD/SCID repopulating function [39]. Furthermore, UCB ALDH high cells are considered to be proangiogenic progenitors that integrate into ischemic tissue and promote vascular regeneration [40]. Isolated HSPCs according to their enhanced ALDH activity in PCB demonstrated a HSPC phenotype and higher in-vitro clonogenic potential than in TCB.…”

Section: Discussionmentioning

confidence: 73%

Hematopoietic Stem Cells in Neonates: Any Differences between Very Preterm and Term Neonates?

et al. 2014

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BackgroundIn the last decades, human full-term cord blood was extensively investigated as a potential source of hematopoietic stem and progenitor cells (HSPCs). Despite the growing interest of regenerative therapies in preterm neonates, only little is known about the biological function of HSPCs from early preterm neonates under different perinatal conditions. Therefore, we investigated the concentration, the clonogenic capacity and the influence of obstetric/perinatal complications and maternal history on HSPC subsets in preterm and term cord blood.MethodsCD34+ HSPC subsets in UCB of 30 preterm and 30 term infants were evaluated by flow cytometry. Clonogenic assays suitable for detection of the proliferative potential of HSPCs were conducted. Furthermore, we analyzed the clonogenic potential of isolated HSPCs according to the stem cell marker CD133 and aldehyde dehydrogenase (ALDH) activity.ResultsPreterm cord blood contained a significantly higher concentration of circulating CD34+ HSPCs, especially primitive progenitors, than term cord blood. The clonogenic capacity of HSPCs was enhanced in preterm cord blood. Using univariate analysis, the number and clonogenic potential of circulating UCB HSPCs was influenced by gestational age, birth weight and maternal age. Multivariate analysis showed that main factors that significantly influenced the HSPC count were maternal age, gestational age and white blood cell count. Further, only gestational age significantly influenced the clonogenic potential of UCB HSPCs. Finally, isolated CD34+/CD133+, CD34+/CD133– and ALDHhigh HSPC obtained from preterm cord blood showed a significantly higher clonogenic potential compared to term cord blood.ConclusionWe demonstrate that preterm cord blood exhibits a higher HSPC concentration and increased clonogenic capacity compared to term neonates. These data may imply an emerging use of HSPCs in autologous stem cell therapy in preterm neonates.

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Section: Discussionmentioning

confidence: 73%

Hematopoietic Stem Cells in Neonates: Any Differences between Very Preterm and Term Neonates?

et al. 2014

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“…Recently, cell-based therapies have attracted a high level of attention as a novel treatment for neonatal encephalopathy [6] . Studies have shown that human umbilical cord blood (hUCB) cell therapies provide beneficial effects in a number of diseases because hUCB cells contain several types of stem cells, such as those expressing the CD34 cell-surface marker (hematopoietic stem/endothelial progenitor cells) [7,8] . In preclinical studies using neonatal models with brain injuries, >10 studies have proven the therapeutic efficacy of hUCB cell treatment.…”

Section: Introductionmentioning

confidence: 99%

Evaluations of Intravenous Administration of CD34<sup>+</sup> Human Umbilical Cord Blood Cells in a Mouse Model of Neonatal Hypoxic-Ischemic Encephalopathy

Ohshima

Taguchi²,

Sato³

et al. 2016

Dev Neurosci

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Several cell therapies have been explored as novel therapeutic strategies for neonatal encephalopathy because the benefits of current treatments are limited. We previously reported that intravenous administration of human umbilical cord blood (hUCB) CD34⁺ cells (hematopoietic stem cells/endothelial progenitor cells) at 48 h after insult exerts therapeutic effects in neonatal mice with stroke, i.e., permanent middle cerebral artery occlusion. Although neonatal stroke and hypoxic-ischemic encephalopathy (HIE) are grouped under the term “neonatal encephalopathy,” their pathogenesis differs. However, little is known about the differences in the effects of the same treatment between these 2 diseases. In this study, we investigated whether the same treatment protocol exerts therapeutic effects in neonatal mice with HIE. The treatment significantly ameliorated the decreased cerebral blood flow in the ischemic penumbra. Although the cylinder and rotarod tests showed a trend of amelioration of behavioral impairments from the treatment, these were not statistically significant. Morphological brain injuries were not altered by treatment. The cell administration did not cause any adverse effects apart from hyperactivity in the open-field test. Some of these findings are consistent with the results obtained in our previous study using a stroke model, but others are not. This study suggests that the treatment protocol needs to be optimized for each pathological condition.

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“…Experimental approaches have been undertaken to enhance regeneration or restore lost functions after stroke with exogenously injected or transplanted human-induced pluripotent stem cells [10], umbilical cord blood-derived aldehyde dehydrogenase-expressing progenitor cells [11], and endothelial progenitor cells from umbilical cord [12]. Recent studies predicted that intensifying neuronal differentiation and survival around the ischemic area can improve the clinical outcome.…”

Section: Introductionmentioning

confidence: 99%

Heme Oxygenase 1-Mediated Neurogenesis Is Enhanced by Ginkgo biloba (EGb 761®) After Permanent Ischemic Stroke in Mice

2013

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Stroke is the fourth leading cause of death and a major cause of disability in stroke survivors. Studies have underlined the importance of repair mechanisms in the recovery phase of stroke. Neurogenesis in response to brain injury is one of the regeneration processes that, if enhanced, may offer better stroke treatment alternatives. Previously, we have demonstrated antioxidant, neuritogenic, and angiogenic properties of Ginkgo biloba/EGb 761® (EGb 761) in different mouse models of stroke. In the present study, we were interested to study whether EGb 761 could protect mice from permanent middle cerebral artery occlusion (pMCAO) and enhance neurogenesis. EGb 761 pre- sand post-treated mice had lower infarct volume and improved motor skills with enhanced proliferation of neuronal stem/progenitor cells (NSPCs) at 24 h and 7 days post-treatment. Netrin-1 and its receptors (DCC and UNC5B) that mediate axonal attraction and repulsion were observed to be over-expressed in NSPCs only, implying that netrin-1 and its receptors might have partly played a role in enhanced neurogenesis. Interestingly, in heme oxygenase 1 knockout mice (HO1-/-), neurogenesis was significantly lower than in vehicle-treated mice at day 7. Furthermore, EGb 761 post-treated mice also demonstrated heme oxygenase 1 (HO1)-activated pathway of phosphorylated glycogen synthase kinase 3-α/β (p-GSK-3 α/β), collapsin response mediator protein 2 (CRMP-2), semaphorin3A (SEMA3A), and Wnt, suggesting probable signaling pathways involved in proliferation, differentiation and migration of NSPCs. Together, these results propose that EGb 761 not only has antioxidant, neuritogenic and angiogenic properties, but can also augment the repair and regeneration mechanisms following stroke.

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Umbilical Cord Blood‐Derived Aldehyde Dehydrogenase‐Expressing Progenitor Cells Promote Recovery from Acute Ischemic Injury

Cited by 49 publications

References 53 publications

Hematopoietic Stem Cells in Neonates: Any Differences between Very Preterm and Term Neonates?

Hematopoietic Stem Cells in Neonates: Any Differences between Very Preterm and Term Neonates?

Evaluations of Intravenous Administration of CD34<sup>+</sup> Human Umbilical Cord Blood Cells in a Mouse Model of Neonatal Hypoxic-Ischemic Encephalopathy

Heme Oxygenase 1-Mediated Neurogenesis Is Enhanced by Ginkgo biloba (EGb 761®) After Permanent Ischemic Stroke in Mice

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