Safety and feasibility of autologous cord blood infusion for improving motor function in young children with cerebral palsy in Japan: A single-center study.

INTRODUCTION: Cerebral palsy (CP) is the most prevalent motor disorder of childhood. It typically results from in utero or perinatal brain injury. Recently, it has been reported that autologous cord blood (ACB) infusion for children with CP improved gross motor function and brain connectivity, but unfortunately, it has never been tried in Japan. We conducted a pilot study of the infusing of ACB, which was delivered from private bank, in the children with CP to assess the safety and feasibility to the procedure as well as any effect in improving neurological function. METHODS: After demonstrating the induction of tissue regeneration in animal model studies conducted a single-arm pilot study of intravenous ACB infusion in 6 young Japanese children with CP (ages 1-6 years). Primary outcomes were safety assessed by vital signs, clinical symptoms, and blood and urinary examinations at baseline and 1 weeks, 1, 2 and 3 years after treatment. In addition, motor function evaluations, neurodevelopmental examinations, magnetic resonance imaging, and electroencephalography (EEG) were performed at the same time. RESULTS: Infusion was generally well-tolerated, although one patient experienced microhematuria 1 year after treatment and another one patient experienced febrile convulsion once 9 months after treatment. These events were transient, no relapse was seen during observation study. All patients improved a median of 6.8 points on the 1-year Gross Motor Functional Measure-66 (GMFM-66) scores, greater than predicted by age and severity. Furthermore, the 2-year and 3-year GMFM-66 scores were also greater than expected (median 6.2 points and 5.5 points, respectively). Overall scales and language-social scales of the developmental quotient (DQ) improved in 3 of 6 patients, who had greater changes in their GMFM-66 scores than the other cases after treatment. There were no significant correlations among the GMFM-66 scores, DQ, and infusion cell counts. CONCLUSION: ACB infusion was safe and feasible for clinical use in patients with CP. However, much more clinical study with larger numbers of patients and in-depth studies of treatment mechanism of CP are needed.

Perinatal Care Preparedness in Kochi Prefecture for When a Nankai Trough Earthquake Occurs: Action Plans and Disaster Liaisons for Pediatrics and Perinatal Medicine.

A Nankai Trough earthquake is highly likely to occur in near future, and perinatal medical resources and care in Kochi Prefecture may be insufficient after such an event. Therefore, we evaluated the medical and public health measures needed to prepare for caring for pregnant women in Kochi Prefecture in the aftermath of such an earthquake and the potential action plans for the prefecture. We estimated that immediately after an earthquake, approximately 30 pregnant women will require urgent medical treatment, most of whom will be in the prefectural capital, Kochi City, and perinatal medical care in Kochi City may be insufficient. Therefore, we used the projected flooding areas to divide Kochi City and its surrounding areas into 3 areas and allocated at least one Disaster Liaison for Pediatrics and Perinatal Medicine (DLPPM) to each disaster base hospital in those 3 areas. In a disaster, the DLPPMs will serve as key individuals in their respective areas and coordinate the allocation of medical care. A DLPPM will be allocated also within the Disaster Medical Response Headquarters of Kochi Prefecture and be responsible for overseeing perinatal care in the whole of Kochi Prefecture. Our study shows that estimating the number of affected pregnant women and requirement for perinatal medical care is an effective way to prepare realistic disaster measures and to enable a specific plan to be formulated for effective allocation and management of DLPPMs. We believe that our system can serve as a model in perinatal disaster medicine.

Tips and Techniques for Laparoscopic Tubal Reanastomosis: A Case Report.

Tubal reanastomosis or tubal reversal, a surgical method used to reverse tubal sterilization, may be an option for women who for various reasons wish to reestablish their fertility. A 38-year-old Chinese woman, gravida 2, para 2 (both delivered through cesarean section) presented to our outpatient gynecology clinic requesting bilateral tubal recanalization. After other causes of infertility were excluded, laparoscopic tubal reanastomosis was performed. Here, we present our tips and techniques for laparoscopic tubal reanastomosis that rapidly resulted in an intrauterine pregnancy, which delivered at term. Laparoscopic tubal reanastomosis is a well-established procedure with good prognosis, as reported in the literature. For women who wish to become pregnant after tubal sterilization, it is necessary to present the option of surgery as well as in vitro fertilization.

Induction of regional chemokine expression in response to human umbilical cord blood cell infusion in the neonatal mouse ischemia-reperfusion brain injury model.

Regenerative medicine using umbilical cord blood (UCB) cells shows promise for the treatment of cerebral palsy. Although the efficacy of this therapy has been seen in the clinic, the mechanisms by which UCB cells interact and aid in the improvement of symptoms are not clear. We explored the chemokine expression profile in damaged brain tissue in the neonatal mouse ischemia-reperfusion (IR) brain injury model that was infused with human UCB (hUCB) cells. IR brain injury was induced in 9-day-old NOD/SCID mice. hUCB cells were administered 3 weeks post brain injury. Chemokine expression profiles in the brain extract were determined at various time points. Inflammatory chemokines such as CCL1, CCL17, and CXCL12 were transiently upregulated by 24 hours post brain injury. Upregulation of other chemokines, including CCL5, CCL9, and CXCL1 were prolonged up to 3 weeks post brain injury, but most chemokines dissipated over time. There were marked increases in levels of CCL2, CCL12, CCL20, and CX3CL1 in response to hUCB cell treatment, which might be related to the new recruitment and differentiation of neural stem cells, leading to the induction of tissue regeneration. We propose that the chemokine expression profile in the brain shifted from responding to tissue damage to inducing tissue regeneration. hUCB cell administration further enhanced the production of chemokines, and chemokine networks may play an active role in tissue regeneration in neonatal hypoxic-ischemic brain injury.

CCL11 promotes migration and proliferation of mouse neural progenitor cells.

BACKGROUND: Neonatal hypoxia-ischemia induces massive brain damage during the perinatal period, resulting in long-term consequences to central nervous system structural and functional maturation. Although neural progenitor cells (NPCs) migrate through the parenchyma and home in to injury sites in the rodent brain, the molecular mechanisms are unknown. We examined the role of chemokines in mediating NPC migration after neonatal hypoxic-ischemic brain injury. METHODS: Nine-day-old mice were exposed to a 120-minute hypoxia following unilateral carotid occlusion. Chemokine levels were quantified in mouse brain extract. Migration and proliferation assays were performed using embryonic and infant mouse NPCs. RESULTS: The neonatal hypoxic-ischemic brain injury resulted in an ipsilateral lesion, which was extended to the cortical and striatal areas. NPCs migrated toward an injured area, where a marked increase of CC chemokines was detected. In vitro studies showed that incubation of NPCs with recombinant mouse CCL11 promoted migration and proliferation. These effects were partly inhibited by a CCR3 antagonist, SB297006. CONCLUSIONS: Our data implicate an important effect of CCL11 for mouse NPCs. The effective activation of NPCs may offer a promising strategy for neuroregeneration in neonatal hypoxic-ischemic brain injury.

Aggressive Angiomyxoma of the Vulva with No Recurrence on a 5-year Follow up: A Case Report.

We report a case of vulvar aggressive angiomyxoma (AA) which is a rare, slow growing and benign tumor of mesenchymal origin, but has a high risk of local recurrence. A 49-year-old Japanese female was referred to us with a large mass of the left vulva, measuring 15×9.5×9 centimeters. She underwent surgical excision of the tumor with no evidence of recurrence on a 5-year follow up. In this case, histopathological examination and immunohistochemical staining after excision revealed a diagnosis of vulvar AA with estrogen and progesterone receptors positive. Aggressive angiomyxoma of the vulva needs to be distinguished from benign myxoid tumor with a low risk of local recurrence as well as from malignant neoplasma. The first line treatment of AA is complete surgical excision with tumor free margins, it will reduce the recurrence.

Syngeneic transplantation of newborn splenocytes in a murine model of neonatal ischemia-reperfusion brain injury.

OBJECTIVE: Neonatal hypoxic-ischemic encephalopathy (HIE) is caused by brain injury that occurs in a developing fetus or infant. Stem cell transplantation can reportedly induce functional recovery in animal models of HIE. Murine neonatal splenocytes are enriched with immature blood stem cells and are used for the investigation of murine models of syngeneic transplantation. The aim of this study was to investigate the therapeutic potential of newborn splenocytes in a murine model of neonatal ischemia-reperfusion brain injury. METHODS: C57BL/6N mice (postnatal day 7) underwent right common carotid artery occlusion with an aneurysm clip. Following hypoxic exposure, reperfusion was achieved by unclamping the artery. Newborn splenocytes were transplanted intravenously at 3 weeks after injury. RESULTS: The splenocytes transplanted group tended to show an improvement in behavioral tests, but it was not significantly different compared with the control groups. The transplanted cells were localized in various organs including injured brain tissue over 3 weeks. In the penumbra region of the brain, vascular endothelial growth factor (VEGF) expression was upregulated after transplantation. CONCLUSIONS: These results showed that syngeneic transplantation of newborn splenocytes achieved the long-term survival of the grafts and exerted influence the microenvironment in the injured brains of mice.

A hierarchical Bayesian framework to infer the progression level to diabetes based on deficient clinical data.

The increase in lifestyle-related diseases such as heart disease, diabetes, and high blood pressure is a challenging problem that should be resolved. The physiological mechanisms of the human body have long been studied using mathematical models. In particular, to study glucose metabolism, several models that infer insulin sensitivity and ß-cell function have been developed. The use of mathematical models to assess progression to diabetes based on clinical data could be effective for preventing the onset of diabetes. However, to assess the progression level, we need clinical data including data from oral glucose tolerance tests, which are not typically performed on patients whose glucose tolerance may be impaired. To address this shortcoming, we developed a hierarchical Bayesian framework to infer the progression of glucose intolerance based on deficient data. We demonstrated how the framework infers the level of progression to diabetes and showed that glucose disposal capacity and insulin-secretory function depend on the fasting glucose and glycated hemoglobin (HbA1c) levels.

The therapeutic potential of human umbilical cord blood transplantation for neonatal hypoxic-ischemic brain injury and ischemic stroke.

Human umbilical cord blood (HUCB) cells are rich source of immature stem cells, which have the potential to repair lost tissue. Intractable central nervous system (CNS) disorders are important targets for regenerative medicine, and the application of HUCB cells is being investigated in animal models of CNS disorders. Transplantation of HUCB has induced functional improvements in these animal models due to multiple therapeutic effects including neuroprotection, anti-inflammation, angiogenesis, and neurogenesis. HUCB cells are easily available and safer than other stem cells used in transplantation therapy. In this review, we focus on HUCB transplantation as an encouraging therapeutic approach for animal models of neonatal hypoxic-ischemic brain injury and ischemic stroke.