Intra-arterial transplantation of human umbilical cord blood mononuclear cells in neonatal hypoxic–ischemic rats

Greggio, Samuel; Paula, Simone de; Azevedo, Pâmella Nunes; Venturin, Gianina Teribele; Costa, Jaderson Costa da

doi:10.1016/j.lfs.2013.10.017

Cited by 37 publications

(22 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The large variation in infarct size makes the small morphological changes undetectable. Several studies on neonatal HIE have reported the beneficial effects of cell therapies in behavioral tests without any morphological improvement [11,36,37]. Such reports show that the lack of morphological improvement does not preclude an improvement in behavior.…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

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

View full text Add to dashboard Cite

show abstract

“…In the report of intra-arterial transplantation [10], the transplant did not restore stereological volume in the damaged tissue even though long-term adverse cognitive effects were reduced. This would suggest that there were positive influences of the transplant on remaining intrinsic cells, but not cell replacement.…”

Section: Summary Of Acute Preclinical Studiesmentioning

confidence: 97%

Stem Cell Therapy for Neonatal Hypoxic–Ischemic Brain Injury

Carroll¹

2015

Cell Therapy for Brain Injury

View full text Add to dashboard Cite

Various varieties of stem cells and methods of their administration are proposed as therapeutic modalities for neonatal hypoxic-ischemic (HI) brain injury. The widespread use of stem cells for this purpose and others, despite the lack of strong clinical evidence for their efficacy in most clinical situations, makes it incumbent to review the pathophysiology of the clinical condition of neonatal HI brain injury, the preclinical data dealing with animal HI injury, and the available clinical studies.The central problem for the evaluation of treatment for neonatal HI injury is that two vastly different circumstances exist with respect to the condition: (1) the acute and (2) the chronic or long-standing result of the acute injury. The pathophysiology of the two variations, particularly with respect to the possible benefit of stem cell treatment, is quite different.The situation is further complicated by the widespread interest in treating cerebral palsy (CP) with stem cells, an effort of great interest to parents and society at large. This effort has been given impetus by anecdotal stories carried on the Internet. However, only a small component of children with CP has neonatal HI brain injury as the cause for their disability. While the treatment of CP is a popular target for stem cell therapy, CP is a group of disorders of complex and varied cause. This chapter deals only with CP caused by HI injury in the neonatal period of the term infant. Pathophysiology of Neonatal Hypoxic-Ischemic InjuryThe pathophysiology of acute HI injury in term infants is well known. These processes are important for our discussion in that they relate to way stem cells interact with the tissue. The mechanism of injury has been summarized in detail by J. Carroll 308 Volpe [1]. Briefly, the key innate factors are the vulnerable vascular border zones, regional anaerobic mechanisms, and excitatory glutamate synapses. Hypercapnia, hypoxemia, and acidosis lead to loss of regional regulation of blood flow. The latter phenomenon, in combination with systemic hypotension, leads to a compounding of the preceding events with exacerbation of the abnormal blood flow, more anaerobic metabolism with increasing lactate, and a rise in the damaging glutamate. As a consequence, cellular adenosine triphosphate (ATP) is depleted, calcium intrudes into the cell, and excitatory amino acids bring about more cellular damage. Later reperfusion injury eventuates leading to more neuronal damage with cell necrosis followed later by apoptosis. Models of acute HI injury, discussed below, attempt to mimic these events.Most of the studies of HI relate most closely to events in the term infant. The brain injuries in premature infants, however, comprise a significant portion of the pathology in patients with CP. While term infants tend to demonstrate more neuronal and cortical injuries, premature infants are more vulnerable to injury of the white matter. The influence of stem cell therapy in white matter injury is even less well understood and is not the subject here.Th...

show abstract

“…Some studies demonstrate that a higher dose is more beneficial [14,38,39], while a study does not confirm it [67].…”

Section: Cell Typementioning

confidence: 99%

Cell-Based Therapies in Neonatal Stroke

Tsuji

Johnston

2015

Cell Therapy for Brain Injury

View full text Add to dashboard Cite

Intra-arterial transplantation of human umbilical cord blood mononuclear cells in neonatal hypoxic–ischemic rats

Abstract: Our findings contribute to the translational knowledge of cell based-therapy in neonatal HI and demonstrate for the first time that IA transplantation into rat pups is a feasible route for cellular delivery and prevents long-term cognitive deficits induced by experimental neonatal HI.

Cited by 37 publications

References 46 publications

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

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

Stem Cell Therapy for Neonatal Hypoxic–Ischemic Brain Injury

Cell-Based Therapies in Neonatal Stroke

Contact Info

Product

Resources

About