scholarly journals Umbilical cord blood therapy modulates neonatal hypoxic ischemic brain injury in both females and males

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tayla R. Penny ◽  
Yen Pham ◽  
Amy E. Sutherland ◽  
Joohyung Lee ◽  
Graham Jenkin ◽  
...  

AbstractPreclinical and clinical studies have shown that sex is a significant risk factor for perinatal morbidity and mortality, with males being more susceptible to neonatal hypoxic ischemic (HI) brain injury. No study has investigated sexual dimorphism in the efficacy of umbilical cord blood (UCB) cell therapy. HI injury was induced in postnatal day 10 (PND10) rat pups using the Rice-Vannucci method of carotid artery ligation. Pups received 3 doses of UCB cells (PND11, 13, 20) and underwent behavioural testing. On PND50, brains were collected for immunohistochemical analysis. Behavioural and neuropathological outcomes were assessed for sex differences. HI brain injury resulted in a significant decrease in brain weight and increase in tissue loss in females and males. Females and males also exhibited significant cell death, region-specific neuron loss and long-term behavioural deficits. Females had significantly smaller brains overall compared to males and males had significantly reduced neuron numbers in the cortex compared to females. UCB administration improved multiple aspects of neuropathology and functional outcomes in males and females. Females and males both exhibited injury following HI. This is the first preclinical evidence that UCB is an appropriate treatment for neonatal brain injury in both female and male neonates.

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1905-1905
Author(s):  
Shinsuke Takagi ◽  
Hideki Araoka ◽  
Naoyuki Uchida ◽  
Masahiro Abe ◽  
Mitsuhiro Yuasa ◽  
...  

Abstract Background: Bloodstream infection (BSI) is one of serious complications after allogeneic hematopoietic cell transplantation (HCT). Several risk factors have been described in previous reports. They included elderly patients, myeloid malignancies, myeloablative conditioning and HLA mismatch. In recent years, the number of umbilical cord blood used as an alternative donor source is rapidly increasing. The interval between transplant and neutrophil engraftment after umbilical cord blood transplantation (UCBT) is longer than that of other stem cell sources, and bacterial infections are one of the most serious concerns after UCBT. However, studies that focus on the impact of donor source on the incidence of BSI and include sufficient number of UCBT are lacking. In the study, we aimed to analyze the impact of umbilical cord blood on the development of BSI after allogeneic HCT retrospectively. Patient and Method: We retrospectively studied the patients who received transplant as first allogeneic HCT in Toranomon Hospital between Apr 2003 and Mar 2014. We analyzed the incidence of BSI that occurred within 100 days after transplant. BSI was defined as isolation of a bacterial or fungal pathogen from at least 1 blood culture, with the exception of coagulase-negative staphylococci (CNS) and normal contaminants (Corynebacterium species, Lactobacillus species, Bacillus species and Propionibacterium species), which required 2 separate blood cultures with the same antibiogram, to be considered a true infection. BSI was considered polymicrobial, if 2 or more pathogens were isolated in a single blood culture. The patients whose blood culture was positive within 2 weeks before transplant and the patients whose performance status (PS) were 4 before transplant were excluded. Result: A total of 1032 patients were extracted. Donors were related peripheral blood stem cell and/or bone marrow (r-PB/BM) in 155 patients, unrelated BM (ur-BM) in 243, and unrelated umbilical cord blood (ur-CB) in 634. The median age of recipient was 49 years (range, 16 - 82). Underlying diseases were as follows; AML (n=458), MDS (n=83), CML (n=30), MPN (n=15), MDS/MPN (n=13), ALL/LBL (n=134), CLL (n=3), AUL (n=9), NHL (n=162), HL (n=17), ATL (n=53), MM (n=16), AA (n=35) and others (n=4). The cumulative incidence of BSI was 47.6% (95% confidence interval, 44.5 - 50.6%) at 100 days after allogeneic HCT. The median onset of first BSI was day 7 (range, 0 - 99) after transplant. In 491 patients who developed BSI, a single pathogen was isolated in 409 patients (gram-positive cocci: GPC in 257, gram-negative rod: GNR in 112, gram-positive rod: GPR in 31, fungus in 9). Of the 491 patients with BSI, two pathogens were isolated in 74 patients (two GPCs in 37, one GPC & one GNR in 20, one GPC & one GPR in 13, two GNRs in 3, one GNR & one GPR in 1) and three pathogens were isolated in 8 patients (three GPCs in 5, two GPCs & one GNR in 1, two GPCs & one GPR in 1, one GPC & two GNRs in 1). Of the 581 isolates, GPCs accounted for 66%. The most frequent isolates in GPCs and GNRs were Staphylococcus epidermidis (34% in GPCs) and Pseudomonas aeruginosa (33% in GNRs), respectively. The cumulative incidence of BSI after transplants from r-PB/BM, ur-BM, ur-CB was 31.7%, 35.0%, 56.3%, respectively (p<0.01). In univariate analysis, age (>49 vs. ≤49, p<0.01), PS (2-3 vs. 0-1, p<0.01), hematologic disease (myeloid vs. others, p=0.01), disease status (not in CR vs. in CR, p<0.01), conditioning regimen (MAC vs. RIC, p<0.01), donor source (ur-CB vs. rPB/BM and ur-BM, p<0.01) had impact on the cumulative incidence of BSI. In multivariate analysis, ur-CB was identified as the most significant risk factor for the development of BSI (hazard ratio 1.60, 95% confidence interval 1.34 - 1.92, p=0.00000017). Conclusion: The study included 634 UCBT and it allowed us to clarify the impact of umbilical cord blood on the development of BSI. We concluded that umbilical cord blood was the most significant risk factor for BSI after allogeneic HCT. BSI should be recognized as a serious complication that emerges in more than a half of recipients in the early phase after UCBT. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.


Author(s):  
Yanqun Chang ◽  
Shouheng Lin ◽  
Yongsheng Li ◽  
Song Liu ◽  
Tianbao Ma ◽  
...  

Abstract 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.


2014 ◽  
Vol 23 (8) ◽  
pp. 959-979 ◽  
Author(s):  
Sheng-Hsien Chen ◽  
Jhi-Joung Wang ◽  
Chung-Hwan Chen ◽  
Hsiu-Kang Chang ◽  
Mao-Tsun Lin ◽  
...  

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S82
Author(s):  
Kyra Chan ◽  
Valerie Zahra ◽  
Vanesa Stojanovska ◽  
Paris Papagianis ◽  
Anqi Li ◽  
...  

2002 ◽  
Vol 11 (3) ◽  
pp. 275-281 ◽  
Author(s):  
Dunyue Lu ◽  
Paul R. Sanberg ◽  
Asim Mahmood ◽  
Yi Li ◽  
Lei Wang ◽  
...  

We measured the effect of treatment of traumatic brain injury (TBI) in the rat with human umbilical cord blood (HUCB) administered IV. HUCB cells were injected into the tail vein 24 h after TBI and the rats were sacrificed at day 28 after the treatment. The Rotarod test and the neurological severity score (NSS) were used to evaluate neurological function. The distribution of the donor cells in the brain, heart, lung, kidney, liver, spleen, bone marrow, and muscle were analyzed in recipient rats using immunohistochemical staining and laser confocal microscopy. HUCB cells injected IV significantly reduced motor and neurological deficits compared with control groups by day 28 after the treatment. The cells preferentially entered the brain and migrated into the parenchyma of the injured brain and expressed the neuronal markers, NeuN and MAP-2, and the astrocytic marker, GFAP. Some HUCB cells integrated into the vascular walls within the boundary zone of the injured area. Our data suggest that IV administration of HUCB may be useful in the treatment of TBI.


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