Stem cell therapy for neonatal brain injury: Perspectives and Challenges

Titomanlio, Luigi; Kavelaars, Annemieke; Dalous, Jérémie; Mani, Shyamala; Ghouzzi, Vincent El; Heijnen, Cobi J.; Baud, Olivier; Gressèns, Pierre

doi:10.1002/ana.22518

Cited by 127 publications

(101 citation statements)

References 190 publications

(397 reference statements)

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“…Most studies of cell therapy in neonatal HI injury use intracerebral transplantation. 7,9 Cell delivery via intravenous or intraperitoneal route is a less invasive method that allows widespread distribution of transplanted cells to cover the injured area. In addition, this peripheral procedure enables exposure of cells to the chemotactic signals at the injury site, which selectively attracts cells to migrate to the target tissue.…”

Section: Strokementioning

confidence: 99%

“…[3][4][5] Stem cells have been used in the experimental studies of neonatal HI. 7 Human umbilical cord blood stem cells (HUCSCs) contain many stem cell types that can differentiate into mature cell types. Many studies have evaluated the effect of HUCSCs in perinatal brain damage; 8,9 however, few studies have focused on the protective effect of human umbilical vein endothelial cells (HUVECs).…”

mentioning

confidence: 99%

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Human Umbilical Vein Endothelial Cells Protect Against Hypoxic-Ischemic Damage in Neonatal Brain via Stromal Cell-derived Factor 1/C-X-C Chemokine Receptor Type 4

Chen

Chang

et al. 2013

Stroke

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Background and Purpose-Agents that protect against neurovascular damage provide a powerful neuroprotective strategy.Human umbilical vein endothelial cells (HUVECs) may be used to treat neonates with hypoxic-ischemia (HI) because of its autologous capability. We hypothesized that peripherally injected HUVECs entered the brain after HI, protected against neurovascular damage, and provided protection via stromal cell-derived factor 1/C-X-C chemokine receptor type 4 pathway in neonatal brain. Methods-Postpartum day 7 rat pups received intraperitoneal injections of low-passage HUVEC-P4, high-passage HUVEC-P8, or conditioned medium before and immediately after HI. HUVECs were transfected with adenovirus-green fluorescent protein for cell tracing. Oxygen-glucose deprivation was established by coculturing HUVEC-P4 with mouse neuroblastoma neuronal cells (Neuro-2a) and with mouse immortalized cerebral vascular endothelial cells (b.End3). Results-HUVEC-P4-treated group had more blood levels of green fluorescent protein-positive cells than HUVEC-P8-treated group 3 hours postinjection. Intraperitoneally injected HUVEC-P4, but not HUVEC-P8, entered the cortex after HI and positioned closed to the neurons and microvessels. Compared with the condition medium-treated group, the HUVEC-P4-treated but not the HUVEC-P8-treated group showed significantly less neuronal apoptosis and blood-brain barrier damage and more preservation of microvessels in the cortex 24 hours after HI. On postpartum day 14, the HUVEC-P4-treated group showed significant neuroprotection compared with the condition medium-treated group. Stromal cell-derived factor 1 was upregulated in the ipsilateral cortex 3 hours after HI, and inhibiting the stromal cell-derived factor 1/C-X-C chemokine receptor type 4 reduced the protective effect of HUVEC-P4. In vitro transwell coculturing of HUVEC-P4 also significantly protected against oxygen-glucose deprivation cell death in neurons and endothelial cells. Conclusions-Cell

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Section: Strokementioning

confidence: 99%

mentioning

confidence: 99%

Human Umbilical Vein Endothelial Cells Protect Against Hypoxic-Ischemic Damage in Neonatal Brain via Stromal Cell-derived Factor 1/C-X-C Chemokine Receptor Type 4

Chen

Chang

et al. 2013

Stroke

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“…A possible role of gender in stem cell treatment for neonatal HIE and stroke is being investigated. 114 …”

Section: Modes Of Cell Death In the Injured Neonatal Brainmentioning

confidence: 99%

Mechanisms of Perinatal Arterial Ischemic Stroke

Fernández-López

Natarajan

Ashwal

et al. 2014

J Cereb Blood Flow Metab

110

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The incidence of perinatal stroke is high, similar to that in the elderly, and produces a significant morbidity and severe long-term neurologic and cognitive deficits, including cerebral palsy, epilepsy, neuropsychological impairments, and behavioral disorders. Emerging clinical data and data from experimental models of cerebral ischemia in neonatal rodents have shown that the pathophysiology of perinatal brain damage is multifactorial. These studies have revealed that, far from just being a smaller version of the adult brain, the neonatal brain is unique with a very particular and age-dependent responsiveness to hypoxia-ischemia and focal arterial stroke. In this review, we discuss fundamental clinical aspects of perinatal stroke as well as some of the most recent and relevant findings regarding the susceptibility of specific brain cell populations to injury, the dynamics and the mechanisms of neuronal cell death in injured neonates, the responses of neonatal blood-brain barrier to stroke in relation to systemic and local inflammation, and the long-term effects of stroke on angiogenesis and neurogenesis. Finally, we address translational strategies currently being considered for neonatal stroke as well as treatments that might effectively enhance repair later after injury.

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“…tem cells have been regarded for their therapeutic potential for the treatment of a wide variety of diseases, especially neurological diseases [1,2]. This notion can be attributed to their intrinsic ability, unlike their more mature cell types, to migrate to sites of pathology including stroke, brain trauma, neoplasms, and neurodegenerative diseases, among others [3][4][5][6].…”

mentioning

confidence: 99%

Human Cerebrospinal Fluid Regulates Proliferation and Migration of Stem Cells Through Insulin-Like Growth Factor-1

Zhu

Feng

Dangelmajer

et al. 2015

Stem Cells and Development

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Mesenchymal stem cells (MSCs) and neural progenitor cells (NPCs) have been regarded for their clinical therapeutic potential for central nervous system (CNS) pathologies. Their potential utility is a result of their intrinsic ability to repair damaged tissues, deliver therapeutic proteins, and migrate to sites of pathology within the brain. However, it remains unclear whether the CNS promotes any changes in these potential therapeutic cells, which would be critical to understand before clinical application. A major component of the CNS is cerebrospinal fluid (CSF). Therefore, the aim of this study was to evaluate the influence that human CSF has on the function of human adipose-derived MSCs (hAMSCs) and human fetal-derived NPCs (hfNPCs) in regard to cell proliferation, survival, and migration. This study demonstrated that human noncancerous CSF promoted proliferation and inhibited apoptosis of hAMSCs and hfNPCs. Preculturing these stem cells in human CSF also increased their migratory speed and distance traveled. Furthermore, insulin-like growth factor-1 (IGF-1) in human CSF enhanced the migration capacity and increased the expression of C-X-C chemokine receptor type 4 (CXCR4) in both stem cell types. These current findings highlight a simple and natural way in which human CSF can enhance the proliferation, migration, and viability of human exogenous primary hAMSCs and hfNPCs. This study may provide insight into improving the clinical efficacy of stem cells for the treatment of CNS pathologies.

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Stem cell therapy for neonatal brain injury: Perspectives and Challenges

Cited by 127 publications

References 190 publications

Human Umbilical Vein Endothelial Cells Protect Against Hypoxic-Ischemic Damage in Neonatal Brain via Stromal Cell-derived Factor 1/C-X-C Chemokine Receptor Type 4

Human Umbilical Vein Endothelial Cells Protect Against Hypoxic-Ischemic Damage in Neonatal Brain via Stromal Cell-derived Factor 1/C-X-C Chemokine Receptor Type 4

Mechanisms of Perinatal Arterial Ischemic Stroke

Human Cerebrospinal Fluid Regulates Proliferation and Migration of Stem Cells Through Insulin-Like Growth Factor-1

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