Document text
Principal Investigator: Bruna Corradetti
Organization: BAYLOR COLLEGE OF MEDICINE
Fiscal Year: 2024
Award: $562,740
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
ABSTRACT
Neural tube defects (NTDs), including spina bifida (SB), have a devastating impact on the health and
development of infants and children, with economic, social, and physical demands or hardships placed on
caregivers. SB affects approximately 2,500 live births per year in the United States, with environmental and
genetic factors playing a role in its etiology. By combining bioengineering and placental-derived stem cell
approaches, the CuRe (Cellular Therapy for In Utero Repair of Myelomeningocele) trial has recently advanced
surgical effectiveness and improved clinical outcomes. However, in utero repair requiring fetal exposure at mid-
pregnancy to reduce the ongoing damage of the exposed spinal cord represents an invasive procedure. By
leveraging our expertise in the synthesis of biomimetic therapeutic strategies able to induce tissue repair by
inducing a regenerative cascade at the site of lesion and in the generation of genetically induced model systems,
this project aims to devise less invasive, novel intervention strategies for endogenous in utero repair of
SB. The overall hypothesis is that by creating a pro-regenerative environment within the amniotic cavity, it is
possible to activate the cellular and molecular cascades required to reduce the severity of SB lesions. To test
these hypotheses, we will i) determine the therapeutic efficacy of amniotic fluid-based cell free strategies to
modulate the in utero environment and reduce the severity of SB in a clinically relevant in-house mouse model
(Fbpk8 knockout mice) (Aim 1) and ii) evaluate the protective and regenerative potential of a biomimetic
thermogel for in utero repair of SB lesions in mouse and rabbit models (Aim 2). The proposed research is
expected to enhance our understanding with respect to the impact of biomimetic strategies inducive of
regeneration on the development of neural tube tissues following genetic and mechanical disruption. The
implications of these therapeutic intervention strategies are timely and critical, as stem cell-based, and
bioengineering approaches are already being deployed clinically in other areas, but a minimally invasive, early
in utero intervention is still needed for families and infants affected by SB.
Terms: <Address><Affect><Amniotic Fluid><Animal Model><Animal Models and Related Studies><Ankle><Aqua Amnii><Area><Back><Biodistribution><Biologic Models><Biological Mimetics><Biological Models><Biomedical Engineering><Biomimetics><Birth Defects><Bladder><Bladder Urinary System><Body Tissues><Care Givers><Caregivers><Causality><Cell Body><Cell Therapy><Cells><Cells Placenta-Tissue><Cerebrospinal Fluid><Child Development><Clinical><Clinical effectiveness><Complex><Congenital Abnormality><Congenital Anatomical Abnormality><Congenital Defects><Congenital Deformity><Congenital Malformation><Data Set><Defect><Development><Diagnosis><Domestic Rabbit><Dorsum><Economics><Effectiveness><Embryo Development><Embryogenesis><Embryonic Development><Environment><Etiology><Extravasation><Family><Fetal Therapies><Fetus><GMO Animals><Gel><Generations><Genetic><Genetically Modified Animals><Gestation><Goals><Health><Hind Brain><House mice><Human><Hyaluronic Acid><Impairment><Implant><Infant><Infant and Child Development><Injections><Interdisciplinary Research><Interdisciplinary Study><Intervention><Intervention Strategies><Intestinal><Intestines><KO mice><Knock-out Mice><Knockout Mice><Knowledge><Leakage><Leg><Lesion><Lifelong disability><Liquid substance><Liquor Amnii><Live Birth><Mechanics><Medical><Medulla Spinalis><Meningomyelocele><Meningomyelocoele><Messenger RNA><Mice><Mice Mammals><Model System><Modeling><Modern Man><Molecular><Multidisciplinary Collaboration><Multidisciplinary Research><Murine><Mus><Mus musculus><Myelomeningocele><Natural regeneration><Nervous System Injuries><Nervous System Trauma><Nervous System damage><Neural Tube Defects><Neural Tube Development><Neural Tube Developmental Defects><Neural tube><Neurological Damage><Neurological Injury><Neurological trauma><Normal Placentoma><Null Mouse><Operative Procedures><Operative Surgical Procedures><Oryctolagus cuniculus><Outcome><Paste substance><Pastes><Pathogenesis><Penetrance><Permanent disability><Placenta><Placenta Embryonic Tissue><Placentome><Pregnancy><Prevalence><Procedures><Progenitor Cells><Public Health><Rabbits><Rabbits Mammals><Regeneration><Regio tarsalis><Research><Rhombencephalon><Route><Schistorrhachis><Severities><Shunt><Shunt Device><Site><Spillage><Spina Bifida><Spinal Cord><Spinal Dysraphia><Spinal Dysraphism><Spinal Nerves><Spinal nerve structure><Stem Cell Development><Surgical><Surgical Interventions><Surgical Procedure><Syringes><System><Temperature><Testing><Therapeutic><Therapeutic Effect><Therapeutic Intervention><Tissues><Treatment Efficacy><United States><amniotic cavity><amniotic fluid derived stem cell><amniotic fluid stem cell><bio-engineered><bio-engineers><bioengineering><biological engineering><bowel><causation><cell mediated therapies><cell-based therapeutic><cell-based therapy><cellular therapeutic><cellular therapy><cerebral spinal fluid><cleft spine><clinical practice><clinical relevance><clinically relevant><co-morbid><co-morbidity><comorbidity><determine efficacy><developmental><disease causation><economic><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><embryo culture><embryo surgery><evaluate efficacy><examine efficacy><exosome><experience><exposed in utero><feasibility testing><fetal exposure><fetus therapy><fluid><forging><hindbrain><hydrocele spinalis><improved><improved mobility><in utero><in utero exposure><in utero surgery><in utero therapy><in vivo><intervention efficacy><intervention therapy><interventional strategy><intra-uterine environmental exposure><intrauterine environmental exposure><liquid><mRNA><malformation><materials science><mechanic><mechanical><minimally invasive><mobility enhancement><mobility improvement><model of animal><mouse model><murine model><nano medicinal><nano medicine><nanomedicinal><nanomedicine><neurotrauma><novel><optimized mobility><placental progenitor><placental stem cell><postnatal><prenatal exposure><prenatal surgery><prenatal therapy><prenatally exposed><preservation><prevent><preventing><progenitor biology><progenitor cell based therapy><progenitor cell biology><progenitor cell development><progenitor cell therapy><progenitor cell treatment><progenitor development><progenitor therapy><progenitor treatment><programs><rachischisis posterior><regenerate><regeneration potential><regenerative><regenerative potential><repair><repaired><shunts><social><spinal fluid><stem><stem and progenitor biology><stem and progenitor cell development><stem and progenitor cell therapy><stem cell based therapy><stem cell biology><stem cell mediated therapy><stem cell therapeutics><stem cell therapy><stem cell treatment><stem cell-based therapeutic><stem cell-based treatment><stem cells><success><surgery><therapeutic efficacy><therapy efficacy><tissue degeneration><tissue repair><urinary bladder>