scholarly journals First Autologous Cord Blood Therapy for Pediatric Ischemic Stroke and Cerebral Palsy Caused by Cephalic Molding during Birth: Individual Treatment with Mononuclear Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
A. Jensen ◽  
E. Hamelmann
Keyword(s):  
Cerebral Palsy ◽  
Ischemic Stroke ◽  
Cord Blood ◽  
Brain Damage ◽  
Mononuclear Cells ◽  
Cord Blood Transplantation ◽  
Rare Event ◽  
Treatment Modalities ◽  
Individual Treatment ◽  
Arterial Ischemic Stroke

Intracranial laceration due to traumatic birth injury is an extremely rare event affecting approximately one newborn per a population of 4.5 million. However, depending on the mode of injury, the resulting brain damage may lead to lifelong sequelae, for example, cerebral palsy for which there is no cure at present. Here we report a rare case of neonatal arterial ischemic stroke and cerebral palsy caused by fetal traumatic molding and parietal depression of the head during delivery caused by functional cephalopelvic disproportion due to a “long pelvis.” This patient was treated by autologous cord blood mononuclear cells (45.8 mL, cryopreserved, TNC2.53×10e8) with a remarkable recovery. Active rehabilitation was provided weekly. Follow-up examinations were at 3, 18, 34, and 57 months. Generous use of neonatal head MRI in case of molding, craniofacial deformity, and a sentinel event during parturition is advocated to enhance diagnosis of neonatal brain damage as a basis for fast and potentially causative treatment modalities including autologous cord blood transplantation in a timely manner.

scholarly journals First Autologous Cell Therapy of Cerebral Palsy Caused by Hypoxic-Ischemic Brain Damage in a Child after Cardiac Arrest—Individual Treatment with Cord Blood

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
A. Jensen ◽  
E. Hamelmann
Keyword(s):  
Cardiac Arrest ◽  
Cerebral Palsy ◽  
Cord Blood ◽  
Brain Damage ◽  
Cord Blood Transplantation ◽  
Individual Treatment ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Active Rehabilitation

Each year, thousands of children incur brain damage that results in lifelong sequelae. Therefore, based on experimental evidence, we explored the therapeutic potential of human cord blood, known to contain stem cells, to examine the functional neuroregeneration in a child with cerebral palsy after cardiac arrest. The boy, whose cord blood was stored at birth, was 2.5 years old and normally developed when global ischemic brain damage occurred resulting in a persistent vegetative state. Nine weeks later, he received autologous cord blood (91.7 mL, cryopreserved,5.75×10e8mononuclear cells) intravenously. Active rehabilitation (physio- and ergotherapy) was provided daily, follow-up at 2, 5, 12, 24, 30, and 40 months. At 2-months follow-up the boy’s motor control improved, spastic paresis was largely reduced, and eyesight was recovered, as did the electroencephalogram. He smiled when played with, was able to sit and to speak simple words. At 40 months, independent eating, walking in gait trainer, crawling, and moving from prone position to free sitting were possible, and there was significantly improved receptive and expressive speech competence (four-word sentences, 200 words). This remarkable functional neuroregeneration is difficult to explain by intense active rehabilitation alone and suggests that autologous cord blood transplantation may be an additional and causative treatment of pediatric cerebral palsy after brain damage.

scholarly journals Epilepsy in children with perinatal arterial ischemic stroke

2021 ◽  
Author(s):  
Fabienne Kühne ◽  
Alexander Jungbluth ◽  
Joanna Schneider ◽  
Christoph Bührer ◽  
Christine Prager ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Ischemic Stroke ◽  
Neonatal Period ◽  
Refractory Epilepsy ◽  
Late Onset ◽  
Cognitive Outcome ◽  
Response To Treatment ◽  
Arterial Ischemic Stroke ◽  
Structural Epilepsy ◽  
Drug Refractory Epilepsy

Purpose: Perinatal ischemic stroke (PIS) is a frequent cause for perinatal brain structure defects resulting in epilepsy, cerebral palsy and disability. Since the severity of symptoms is variable, the aim of this study was to evaluate the outcome of children with PIS and seizures/epilepsy to aid parental counseling and therapy decisions. Material: We studied retrospectively patients with arterial PIS and structural epilepsy or seizures in the newborn treated at a single center in 2000-2019. Specifically, signs and symptoms of cerebral palsy (CP), developmental and motor delay, epilepsy and thrombophilia were assessed. Results: From the identified 69 individuals with arterial PIS, we only included the 50 patients (64% male) who had structural epilepsy at the time of investigation or previously in their medical history.The mean age of the included patients was 7.1 years (range 0.08-22) at last consultation. Infarct localisation was predominantly unilateral (86%), left sided (58%) and affecting the middle cerebral artery (94%). Genetic thrombophilia was identified in 52% of the patients examined with genetic testing. More than half of the individuals had CP (52%), and 38.5% had a cognitive outcome below average. First seizures occurred in the neonatal period in 58% of patients and developed into drug-refractory epilepsy in 24.1%. Children with late-onset of epilepsy were twice as likely to develop drug-refractory epilepsy (52.4%). Discussion: Our study shows that patients with PIS and seizures as common sequela often also develop CP. Children with later onset of epilepsy have a worse outcome. Patients with seizure onset in the neonatal period and reccuring seizures have a good response to treatment. Therefore, early diagnosis, follow-up examination and adequate therapy are important. Most children need intensive physiotherapy and speech therapy; however, participation in life is usually age-appropriate.

Cerebral Palsy After Perinatal Arterial Ischemic Stroke

2008 ◽  
Vol 23 (3) ◽  
pp. 279-286 ◽  
Author(s):  
Meredith R. Golomb ◽  
Bhuwan P. Garg ◽  
Chandan Saha ◽  
Faouzi Azzouz ◽  
Linda S. Williams
Keyword(s):  
Cerebral Palsy ◽  
Ischemic Stroke ◽  
Arterial Ischemic Stroke ◽  
Perinatal Arterial Ischemic Stroke

Cord blood transplantation provides better reconstitution of hematopoietic reservoir compared with bone marrow transplantation

Blood ◽  
2003 ◽  
Vol 102 (3) ◽  
pp. 1138-1141 ◽  
Author(s):  
Francesco Frassoni ◽  
Marina Podestà ◽  
Rita Maccario ◽  
Giovanna Giorgiani ◽  
Gabriele Rossi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
Cord Blood Transplantation ◽  
Hematopoietic Progenitor Cell ◽  
Transplant Recipients ◽  
Platelet Recovery ◽  
Blood Transplantation

Abstract Delayed hematopoietic recovery is the main factor precluding a wider use of cord blood (CB) transplants. We hypothesized that this delayed engraftment might not be related to an insufficient number of stem cells in the graft, but to an intrinsic difficulty of these cells to undergo differentiation. To test our hypothesis, 2 groups of children were compared; 12 received a CB transplant and 12 an adult bone marrow (BM) transplant. We studied neutrophil and platelet recovery and, at a median time of approximately 1 year after transplantation, the frequency of colony-forming cells (CFCs) and long-term culture initiating cells (LTC-ICs) in the BM of the 2 groups. Recipients of BM transplants received 1-log more cells and had significantly faster neutrophil and platelet recovery. Conversely, the frequency of committed and early progenitors was significantly higher in the BM of children given CB cells compared with BM transplant recipients (median count of CFC/2 × 104 BM mononuclear cells, 20 versus 11, P = .007; median count of LTC-IC/106 BM mononuclear cells, 8.2 versus 0.2 P = .001). CB, but not adult BM stem cells, can better restore the host hematopoietic progenitor cell reservoir; the delayed engraftment after CB transplantation may reflect the difficulty of CB progenitors to reprogram themselves toward differentiation.

Establishment of a Murine Model of Allogeneic Umbilical Cord Blood Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4600-4600
Author(s):  
Yi Wang ◽  
Wu Depei ◽  
Guanghua Chen ◽  
Aining Sun
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Mononuclear Cells ◽  
Cord Blood Transplantation ◽  
Umbilical Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Adult Mice ◽  
Blood Mononuclear Cells ◽  
Cord Blood Mononuclear Cells

Abstract This study was undertaken to establish a murine model of unrelated allogeneic umbilical cord blood transplantation (UCBT). To investigate the potential possibility to reconstitute the immunohematopietic system in adult mice recipients across major histocompatibility complex by mixed 2 near term cord blood transplantation: 1×106 umbilical cord blood mononuclear cells from 20 day old C57BL/6 (H2b) pups and 1×106 umbilical cord blood mononuclear cells from 20 day old C3H (H2k) mixed pups delivered by cesarean were injected into lethally irradiated (8.0Gy) BALB/c (H2d) adult mice in the same time. After one month, anti-H2b and anti-H2k antibody were used to investigate donor chimera in recipients. Results showed that all of the control mice that reconstituted with only 1×106 umbilical cord blood mononuclear cells from 20-day-old C57BL/6 (H2b) pups died with in three weeks after radiation. 70% recipients that reconstituted with mixed umbilical cord blood mononuclear cells survived in the observation period of three months. Two donors mixed chimera was demonstrated by using anti-H2b and anti-H2k antibody in the same recipient. In vitro mixed lymphocyte response showed immune tolerance. The results confirmed that two kinds of umbilical cord blood can form mixed chimera in the same adult mice recipients. Mixed umbilical cord blood transplantation can reconstitute the immunohematopietic system in adult mice recipients without causing serious GVHD. This model may be suitable to address many questions raised in clinical mixed umbilical cord blood transplantation.

Human Cord Blood Transplantation in a Neonatal Rat Model of Hypoxic–Ischemic Brain Damage: Functional Outcome Related to Neuroprotection in the Striatum

2010 ◽  
Vol 19 (3) ◽  
pp. 351-358 ◽  
Author(s):  
Pedro M. Pimentel-Coelho ◽  
Elizabeth S. Magalhães ◽  
Laudelino M. Lopes ◽  
Leonardo C. deAzevedo ◽  
Marcelo F. Santiago ◽  
...  
Keyword(s):  
Cord Blood ◽  
Functional Outcome ◽  
Brain Damage ◽  
Rat Model ◽  
Cord Blood Transplantation ◽  
Neonatal Rat ◽  
Human Cord Blood ◽  
Ischemic Brain ◽  
Blood Transplantation ◽  
Neonatal Rat Model

scholarly journals A Murine Model for Human Cord Blood Transplantation: Near-Term Fetal and Neonatal Peripheral Blood Cells Can Achieve Long-Term Bone Marrow Engraftment in Sublethally Irradiated Adult Recipients

Blood ◽  
1997 ◽  
Vol 89 (3) ◽  
pp. 1089-1099 ◽  
Author(s):  
Andromachi Scaradavou ◽  
Luis Isola ◽  
Pablo Rubinstein ◽  
Yelena Galperin ◽  
Vesna Najfeld ◽  
...  
Keyword(s):  
Cord Blood ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Near Term ◽  
Ex Vivo Culture

Abstract The purposes of the research reported here were first to explore a murine model for human placental and umbilical cord blood transplantation and second to evaluate the engraftment ability of ex vivo cultured hematopoietic cells. Murine near-term fetal and neonatal peripheral blood (FNPB) cells, genetically marked with the human multiple drug resistance transgene (MDR1) were used for syngeneic transplants into sublethally irradiated adult mice. Donor cells were transplanted either fresh and untreated, or after ex vivo culture in the presence of the hematopoietic growth factors recombinant murine stem cell factor, recombinant human interleukin-3 (rHu IL-3), and rHu IL-6, in a liquid culture system. To evaluate, count, and characterize FNPB progenitor cell-derived colonies, neonatal mouse mononuclear cells were cultured directly in methylcellulose with growth factors. To assess their ex vivo expansion ability, FNPB mononuclear cells were first cultured in liquid medium for 3 to 8 days and then transferred to semisolid assay plates. Evaluation of the cell counts after liquid culture showed a 1.4- to 11.6-fold increase, and the numbers of colonies observed in methylcellulose were similar to those produced by fresh FNPB cells. Donor-type engraftment was demonstrated by polymerase chain reaction (PCR) amplification of the human MDR1 transgene in the peripheral blood of all surviving animals (5 of 7 recipients of the fresh, and 3 of 8 recipients of the ex vivo–cultured cells) 2 to 4 months after transplantation. The proportion of donor leukocytes in the peripheral blood of the recipients (chimerism) was evaluated using fluorescence in situ hybridization (FISH) analysis 4 to 6 months after transplantation and ranged from 2% to 26%. In addition, bone marrow cultures were obtained from two recipient animals: one had received fresh-untreated cells and was evaluated 8 months after transplant, the other had received ex vivo cultured cells and was tested 14 months after grafting. The derived hematopoietic colonies were tested by PCR and the transgene was detected, conclusively proving long-term engraftment of donor cells. These results indicate that FNPB transplants can be successfully performed in sublethally irradiated mice with and without ex vivo culture. Long-term donor-type engraftment with sustained chimerism has been demonstrated. Thus, murine neonatal blood grafts can be used as an animal model for cord blood transplantation for gene therapy studies where complete myeloablation is not desirable and partial replacement of defective marrow may be sufficient. Furthermore, the possibility of numerically expanding hematopoietic progenitor cells contained in neonatal blood without affecting their engraftment ability could facilitate use of cord blood grafts in adult recipients.

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