Multiple doses of umbilical cord blood cells improve long-term brain injury in the neonatal rat

Penny, Tayla; Pham, Yen; Sutherland, Amy E.; Mihelakis, Jamie; Lee, Joohyung; Jenkin, Graham; Fahey, Michael; Miller, Stephanie; McDonald, Courtney

doi:10.1016/j.brainres.2020.147001

Cited by 24 publications

(34 citation statements)

References 57 publications

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“…In this study, a single dose of CD34 + HSCs improved longterm behavioral outcomes and restored neuronal numbers. The result was roughly consistent with the study conducted by Penny TR et al (Penny TR et al 2020) [41] which administrated SD rats multiple doses of UCB and modulated pathological evidence of long-term brain injury better than the study conducted by Penny TR et al (Penny TR et al 2019) [42] which administrated SD rats by a single dose of UCB. According to the above comparisons, we speculated that hypoxic-ischemic injury; CD34 + : HSC transplantation; CD34 -: CD34cells transplantation.…”

Section: Discussionsupporting

confidence: 90%

Umbilical cord blood CD34+ cells administration improved neurobehavioral status and alleviated brain injury in a mouse model of cerebral palsy

Chang

Lin

et al. 2021

Childs Nerv Syst

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Purpose Cerebral palsy (CP) is the most common neuromuscular disease in children, and currently, there is no cure. Several studies have reported the benefits of umbilical cord blood (UCB) cell treatment for CP. However, these studies either examined the effects of UCB cell fraction with a short experimental period or used neonatal rat models for a long-term study which displayed an insufficient immunological reaction and clearance of human stem cells. Here, we developed a CP model by hypoxia-ischemic injury (HI) using immunodeficient mice and examined the effects of human UCB CD34+ hematopoietic stem cells (HSCs) on CP therapy over a period of 8 weeks. Methods Sixty postnatal day-9 (P9) mouse pups were randomly divided into 4 groups (n = 15/group) as follows: (1) sham operation (control group), (2) HI-induced CP model, (3) CP model with CD34+ HSC transplantation, and (4) CP model with CD34- cell transplantation. Eight weeks after insult, the sensorimotor performance was analyzed by rotarod treadmill, gait dynamic, and open field assays. The pathological changes in brain tissue of mice were determined by HE staining, Nissl staining, and MBP immunohistochemistry of the hippocampus in the mice. Results HI brain injury in mice pups resulted in significant behavioral deficits and loss of neurons. Both CD34+ HSCs and CD34- cells improved the neurobehavioral statuses and alleviated the pathological brain injury. In comparison with CD34- cells, the CD34+ HSC compartments were more effective. Conclusion These findings indicate that CD34+ HSC transplantation was neuroprotective in neonatal mice and could be an effective therapy for CP.

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Section: Discussionsupporting

confidence: 90%

Umbilical cord blood CD34+ cells administration improved neurobehavioral status and alleviated brain injury in a mouse model of cerebral palsy

Chang

Lin

et al. 2021

Childs Nerv Syst

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“…Different routes of UCB cell administration were also used (intravenous, intraventricular, intra-arterial, intranasal, and intraperitoneal). Nonetheless, most studies report a positive effect of UCB cell treatment in this model for HIE, namely a long-term recovery of the animals' cognitive and motor functions [36][37][38][39][40][41][42][43][44][45][46][47]. Interestingly, two studies reported no improvement in the functional outcome after UCB cell administration [77,86].…”

Section: Umbilical Cord Blood Cellsmentioning

confidence: 98%

“…There is increasing evidence that stem cell therapy could have positive effects after a hypoxic-ischemic insult in the perinatal period. Several positive outcomes were identified in in vivo studies: improved functional outcome , increased angiogenesis [30,72], increased neurotrophic and growth factors levels [34,53,[72][73][74], and cell proliferation [46,57,61]; reduction in the extension of brain damage [31,43,48,50,53,56,58-63, 71,75,76], translated in decreased apoptosis [31,32,34,36,37,42,45,[48][49][50]54,64,72,73,[76][77][78]; decreased microglial activation and/or astrogliosis [32,[34][35][36][37]40,42,43,45,46,[48][49][50]54,57,62,69,73,75,<...>…”

Section: The Potential Of Stem Cell Therapy For Hiementioning

confidence: 99%

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Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Systematic Review of Preclinical Studies

Serrenho

Rosado

Dinis

et al. 2021

IJMS

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Neonatal hypoxic-ischemic encephalopathy (HIE) is an important cause of mortality and morbidity in the perinatal period. This condition results from a period of ischemia and hypoxia to the brain of neonates, leading to several disorders that profoundly affect the daily life of patients and their families. Currently, therapeutic hypothermia (TH) is the standard of care in developing countries; however, TH is not always effective, especially in severe cases of HIE. Addressing this concern, several preclinical studies assessed the potential of stem cell therapy (SCT) for HIE. With this systematic review, we gathered information included in 58 preclinical studies from the last decade, focusing on the ones using stem cells isolated from the umbilical cord blood, umbilical cord tissue, placenta, and bone marrow. Outstandingly, about 80% of these studies reported a significant improvement of cognitive and/or sensorimotor function, as well as decreased brain damage. These results show the potential of SCT for HIE and the possibility of this therapy, in combination with TH, becoming the next therapeutic approach for HIE. Nonetheless, few preclinical studies assessed the combination of TH and SCT for HIE, and the existent studies show some contradictory results, revealing the need to further explore this line of research.

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“…Penny et al 44 examined the effects of the intraperitoneal administration of hUCB-MNCs 24 h after HI in a neonatal rat model and found that the cell treatment decreased HI-induced microglial activation. They also examined the treatment effect of multiple UCBC administrations: 24 h; 72 h; and 10 days after insult.…”

Section: Activated Microgliamentioning

confidence: 99%

Diverse actions of cord blood cell therapy for hypoxic‐ischemic encephalopathy

Sato

Tsuji

2021

Pediatrics International

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Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal death and permanent neurological deficits. However, effective treatments have not yet been established, except therapeutic hypothermia, which is not effective for severe HIE; therefore, developing a novel therapy for HIE is of the utmost importance. Stem cell therapy has recently been identified as a novel therapy for HIE. Among the various stem cell sources, ethical hurdles can be avoided by using stem cells that originate from non-embryonic or non-neural tissues, such as umbilical cord blood cells (UCBCs), which are readily available and can be exploited for autologous transplantations. Human UCBs are a rich source of stem and progenitor cells. Many recent studies have reported the treatment effect of UCBCs. Additionally, phase I clinical trials have already been conducted, showing this therapy's safety and feasibility. One advantage of stem cell therapies, including UCBC administration, is that they exert treatment effects through multifaceted mechanisms. According to the findings of several publications, replacement of lost cells, namely, engraftment and differentiation into neuronal cells, is not likely to be the main mechanism. However, the association between UCBCs and various mechanism of action, such as neurogenesis, angiogenesis, and anti-inflammation, has been suggested in many studies, and most mechanisms are due to growth factors secreted from UCBCs. These diverse actions of UCBC treatment are expected to exert a substantial effect on HIE, which has a complex injury mechanism.

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Multiple doses of umbilical cord blood cells improve long-term brain injury in the neonatal rat

Cited by 24 publications

References 57 publications

Umbilical cord blood CD34+ cells administration improved neurobehavioral status and alleviated brain injury in a mouse model of cerebral palsy

Umbilical cord blood CD34+ cells administration improved neurobehavioral status and alleviated brain injury in a mouse model of cerebral palsy

Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Systematic Review of Preclinical Studies

Diverse actions of cord blood cell therapy for hypoxic‐ischemic encephalopathy

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