Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy.
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2014-05
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Abstract
Objective
To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE).Study design
We enrolled infants in the intensive care nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to 4 doses adjusted for volume and red blood cell content, 1-5 × 10(7) cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post-infusion vital signs. As exploratory analyses, we compared cell recipients' hospital outcomes (mortality, oral feeds at discharge) and 1-year survival with Bayley Scales of Infant and Toddler Development, 3rd edition scores ≥85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells.Results
Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 mL. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1-year outcomes survived with scores >85.Conclusions
Collection, preparation, and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed.Type
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Cotten, C Michael, Amy P Murtha, Ronald N Goldberg, Chad A Grotegut, P Brian Smith, Ricki F Goldstein, Kimberley A Fisher, Kathryn E Gustafson, et al. (2014). Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. The Journal of pediatrics, 164(5). pp. 973–979.e1. 10.1016/j.jpeds.2013.11.036 Retrieved from https://hdl.handle.net/10161/24697.
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Scholars@Duke
Charles Michael Cotten
I am involved in 4 major areas of research:
1) Neuroprotection. Working with colleagues from Cell Therapies, we have added to Duke's experience participating in pivotal trials of hypothermia for term newborns with moderate to severe hypoxic-ischemic encephalopathy (HIE) by completing, with Duke CTSI support, phase I studies of autologous cord blood cells and allogeneic cord tissue derived mesenchymal stromal cells for these infants. and developing and currently leading a multicenter, double-blind randomized clinical trial of autologous cord blood cells or placebo in term infants with moderate or severe HIE.
2) Genomics. We at Duke have been in the NICHD Neonatal Research Network (NRN) since 2001. I led the NRN's development of an Anonymized DNA bank of samples collected from 1,000 extremely low birthweight infants, with phenotype information linked to the samples. This resource has been the basis for multiple candidate gene, and genome wide scan analysis, and has identified variants associated with severe retinopathy of prematurity and necrotizing enterocolitis. We partnered with the Vermont Oxford Network-Rady Genomics collaborative to bring 48 hour turnaround Whole Genome Sequencing to patients in the Duke Intensive Care Nursery, and are continuing work with Medical Genetics faculty to keep Duke at the forefront of testing the effectiveness of applied next-gen sequencing in the NICU.
3) New Technologies: I collaborated with Drs. David Millington from Duke and Vamsee Pamula (a Duke Pratt School graduate), from BAEBIES Inc, on prototype new technology devices for use in newborn screening for lysosomal storage disease as well as multiplex chips for screening for hyperbilirubinemia and related conditions, as well as working with Dr. Pamula and Dr. Michael Freemark (Peds Endocrinology) on screening panels for hypoglycemia and hypothyroidism, and with investigators from UAB on an Acute Kidney Injury panel. I continue active collaborations with Dr. Cynthia Toth and the DARSI lab in pediatric ophthalmology, and Pratt School investigators to develop and apply use of optical coherence tomography (OCT) for retinal imaging that will assess associations between retinal neurovascular development, brain development, and neurodevelopmental outcomes. We continue with a comparative trial of the value and effectiveness of utilization of OCT compared with the current standard indirect ophthalmoscopy for ROP screening in the NICU.
4)Microbiome in Micropreemies and health outcomes of periviable infants. I have worked with multiple epidemiology researchers to assess practice variation within our center, and within the Neonatal Research Network centers, to identify how variation in practice can influence outcomes, with a particular focus on antibiotic use. This work demonstrated strong associations between high empirical antibiotic use in infants with sterile cultures and subsequent morbidities and mortality. This discovery has led to strong collaborations and new initiatives by early career faculty leading studies of the evolving microbiome, leading to hypothesis generation re: the microbiome and optimal growth in extremely preterm infants.
Ronald Norman Goldberg
1. Perinatal asphyxia and neuroprotection - use of umbilical cord blood transfusion
2. Persistent Pulmonary hypertension - use of ethyl nitrite
3. The extremely low-birth-weight infant.
4. Newborn screening - use of digital microfluidics
Kathryn E. Gustafson
My scholarly interests and expertise are in pediatric neurodevelopmental outcomes assessment and research as well as child and parent coping with chronic childhood illness. In the 1990s, I collaborated with Dr. Robert Thompson in investigating the transactional biopsychosocial model of adaptation to pediatric conditions in children and families. Our research program was funded by the NIH and culminated in the publication of our book, Adaptation to Chronic Childhood Illness. Since that time, I have worked closely with the Division of Neonatology and the Duke Neonatal-Perinatal Research Unit on neurodevelopmental outcomes research with high-risk infants, toddlers, and school-age children. I am a gold standard psychology consultant to the Neonatal Research Network (NRN) of the NIH/NICHD, train and certify psychologists nationally and internationally in infant and toddler developmental assessment for numerous research groups, and serve as consultant for protocol development. In addition, I collaborate with colleagues in Pediatric Ophthalmology to investigate preterm optic nerve anatomy assessed via optical coherence tomography imaging and the association with neurodevelopment. I am also involved in investigations of umbilical cord blood stem cell transplant for young children with hypoxic ischemic encephalopathy, cerebral palsy, and inborn errors of metabolism, such as Krabbe disease, with colleagues in the Pediatric Transplant and Cellular Therapy program.
Geeta Krishna Swamy
Geeta Swamy, MD, Haywood Brown, MD Distinguished Professor of Women’s Health, serves as Executive Vice Dean for Clinical Sciences & Research Administration for the Duke University School of Medicine and Associate Vice President for Research for Duke University. In these roles, Dr. Swamy oversees central operations aligned with clinical departments and research centers, facilitating research priorities in collaboration with clinical chairs and vice chairs, and managing research administration and compliance. She works closely with leadership across the Duke Health Integrated Practice (DHIP) and Duke University Health System (DUHS) on areas that intersect with the academic missions. She collaborates with leaders across the Duke University campus to provide a consistent vision for research administration, operations, quality, and accountability. Her responsibilities include overseeing pre- and post-award management for sponsored grants and contracts, human research, research quality, compliance, and integrity, conflict of interest, and other regulatory areas. As a highly accomplished clinician-scientist, Dr. Swamy’s research specializes in perinatal infection, maternal immunization, and complications of pregnancy.
Joanne Kurtzberg
Dr. Kurtzberg is an internationally renowned expert in pediatric hematology/oncology, pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation, and novel applications of cord blood and birthing tissues in the emerging fields of cellular therapies and regenerative medicine. Dr. Kurtzberg serves as the Director of the Marcus Center for Cellular Cures (MC3), Director of the Pediatric Transplant and Cellular Therapy Program, Director of the Carolinas Cord Blood Bank, and Co-Director of the Stem Cell Transplant Laboratory at Duke University. The Carolinas Cord Blood Bank is an FDA licensed public cord blood bank distributing unrelated cord blood units for donors for hematopoietic stem cell transplantation (HSCT) through the CW Bill Young Cell Transplantation Program. The Robertson GMP Cell Manufacturing Laboratory supports manufacturing of RETHYMIC (BLA, Enzyvant, 2021), allogeneic cord tissue derived and bone marrow derived mesenchymal stromal cells (MSCs), and DUOC, a microglial/macrophage cell derived from cord blood.
Dr. Kurtzberg’s research in MC3 focuses on translational studies from bench to bedside, seeking to develop transformative clinical therapies using cells, tissues, molecules, genes, and biomaterials to treat diseases and injuries that currently lack effective treatments. Recent areas of investigation in MC3 include clinical trials investigating the safety and efficacy of autologous and allogeneic cord blood in children with neonatal brain injury – hypoxic ischemic encephalopathy (HIE), cerebral palsy (CP), and autism. Clinical trials testing allogeneic cord blood are also being conducted in adults with acute ischemic stroke. Clinical trials optimizing manufacturing and testing the safety and efficacy of cord tissue MSCs in children with autism, CP and HIE and adults with COVID-lung disease are underway. DUOC, given intrathecally, is under study in children with leukodystrophies and adults with primary progressive multiple sclerosis.
In the past, Dr. Kurtzberg has developed novel chemotherapeutic drugs for acute leukemias, assays enumerating ALDH bright cells to predict cord blood unit potency, methods of cord blood expansion, potency assays for targeted cell and tissue based therapies. Dr. Kurtzberg currently holds several INDs for investigational clinical trials from the FDA. She has also trained numerous medical students, residents, clinical and post-doctoral fellows over the course of her career.
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