Umbilical Cord Blood Infusion Research Articles

Autologous umbilical cord blood infusion for the treatment of autism in young children: A within‐subjects open label study on safety (assessed via caregiver report) and efficacy

Autologous umbilical cord blood infusion for the treatment of autism in young children: A within‐subjects open label study on safety (assessed via caregiver report) and efficacy

Maintenance of the synergistic effects of cord blood cells and erythropoietin combination therapy after additional cord blood infusion in children with cerebral palsy: 1-year open-label extension study of randomized placebo-controlled trial

BackgroundThis 1-year open-label extension study aimed to identify the persistent synergistic effects of allogeneic umbilical cord blood (UCB) cells and erythropoietin (EPO) in children with cerebral palsy (CP) for up to 2 years.MethodsThis open-label extension study followed children with CP who were enrolled in the previous randomized, double blind, placebo-controlled trial. The following groups from the first trial were maintained: (A) UCB + EPO, (B) UCB, (C) EPO, and (D) only placebo, and all the participants had continued active rehabilitation. This extended study started 3 months after termination of the first trial, which had a 1-year follow-up duration. All subjects received single additional UCB intravenous infusion at the extension baseline regardless of their initial allocation. Outcome measures were the gross motor performance measure (GMPM), gross motor function measure-66 (GMFM-66), and Bayley scales of infant development-II (BSID-II), which were followed at 3, 6, and 12 months after the extension baseline. Changes in the outcome scores from the baseline values of the previous trial and this study were analysed.ResultsSixty-nine children (4.29 ± 1.28 years, M:F = 34:35) were included in this study. Each group showed improvements in the outcome measures at 12 months after additional UCB infusion compared to the baseline scores, except for GMFM and GMPM in Group C which were elevated at 3 and 6 months post-therapy. Total subject analyses did not show significant differences in the outcome measures between the four different groups at 3, 6 and 12 months after additional UCB therapy. However, patients with severe dysfunction, whose GMFCS levels were IV and V, revealed a larger improvement of the GMPM score in Group A than in Group D (Ps < 0.05) from the baseline value of the previous trial. The changes in BSID-II mental scale scores were positively correlated with the number of administered total nucleated cells per unit body weight during this one-year extension study period (r = 0.536, P = 0.001).ConclusionsThese results suggest that when administering UCB to treat patients with CP, combination therapy with EPO is more effective, and the effect might last as long as 2 years, especially in patients with severe impairments.Trial registration: CHA Bundang Medical Center IRB, No. 2015–06-093, approved on July 29, 2015, (https://www.e-irb.com:3443/devlpg/nlpgS200.jsp), ClinicalTrials.gov, NCT03130816, retrospectively registered on April 27, 2017 (https://clinicaltrials.gov/ct2/show/NCT03130816?term=NCT03130816&draw=2&rank=1).

Safety and Efficacy of Allogeneic Umbilical Cord Blood Therapy for Global Development Delay and Intellectual Disability.

Most pediatric patients with global developmental delay (GDD) or intellectual disability (ID) have disrupted development. Since allogeneic umbilical cord blood (UCB) may exert neurotrophic effects, a prospective clinical trial was conducted to assess the efficacy and safety of UCB therapy for GDD and ID. A total of 13 children (ages 23-149 months) with GDD and ID were enrolled and followed up for 12 months. Under criteria of histocompatibility and cell number, allogeneic UCB units were selected and infused once intravenously, and adverse events were monitored. The Bayley Scale of Infant Development-II (BSID-II) was used as primary outcome measurement tool, and evaluations for various functional abilities were also implemented. Safety assessment did not reveal significant adverse effects. Functional improvements in mental and motor developments along with daily living activities and languages were observed at 12 months postintervention compared with the baseline abilities (P < 0.05). Furthermore, mental developmental quotient derived from BSID-II mental scale revealed significantly facilitated improvement during the first 3 months (P < 0.05). In the survey conducted 80.7 ± 13.0 months after UCB infusion to assess satisfaction and long-term safety, no long-term adverse effects were reported, and 70% of the guardians reported satisfaction with the UCB infusion. Long-term changes in two patients who were regularly followed up beyond the study completion were noticeable. One case observed for 4 years showed dramatic improvement until 12 months after UCB therapy, whereas she showed insignificant improvement beyond 12 months after the therapy. Another case showed alleviation of autism with findings of anti-inflammatory response in his peripheral blood after UCB infusion. This clinical study provides support for further applications of UCB as a therapeutic avenue for children with GDD or ID owing to its safety and partial efficacy. Due to patient heterogeneity, further studies focusing on specific clinical manifestations and etiologies are required. Registered at www.clinicaltrials.gov (NCT01769716).

Changes in the geometry and robustness of diffusion tensor imaging networks: Secondary analysis from a randomized controlled trial of young autistic children receiving an umbilical cord blood infusion.

Diffusion tensor imaging (DTI) has been used as an outcome measure in clinical trials for several psychiatric disorders but has rarely been explored in autism clinical trials. This is despite a large body of research suggesting altered white matter structure in autistic individuals. The current study is a secondary analysis of changes in white matter connectivity from a double-blind placebo-control trial of a single intravenous cord blood infusion in 2-7-year-old autistic children (1). Both clinical assessments and DTI were collected at baseline and 6 months after infusion. This study used two measures of white matter connectivity: change in node-to-node connectivity as measured through DTI streamlines and a novel measure of feedback network connectivity, Ollivier-Ricci curvature (ORC). ORC is a network measure which considers both local and global connectivity to assess the robustness of any given pathway. Using both the streamline and ORC analyses, we found reorganization of white matter pathways in predominantly frontal and temporal brain networks in autistic children who received umbilical cord blood treatment versus those who received a placebo. By looking at changes in network robustness, this study examined not only the direct, physical changes in connectivity, but changes with respect to the whole brain network. Together, these results suggest the use of DTI and ORC should be further explored as a potential biomarker in future autism clinical trials. These results, however, should not be interpreted as evidence for the efficacy of cord blood for improving clinical outcomes in autism. This paper presents a secondary analysis using data from a clinical trial that was prospectively registered with ClinicalTrials.gov(NCT02847182).

3.43 More Severe Executive Function Impairments Are Associated With Increases in Frontal Theta and Decreases in Beta and Gamma EEG Power in Young Children With ASD

3.43 More Severe Executive Function Impairments Are Associated With Increases in Frontal Theta and Decreases in Beta and Gamma EEG Power in Young Children With ASD

A multicentre trial of intensive immunosuppressive therapy combined with umbilical cord blood for the treatment of severe aplastic anaemia

Immunosuppressive therapy (IST) is an effective treatment regimen for severe aplastic anaemia (SAA) patients without HLA-identical donors. This study further compared the outcomes between IST and IIST-UCB in SAA on the basis of research shown that IST combined with umbilical cord blood infusion (IIST-UCB) treated effectively. A total of 123 patients from 11 hospitals in China were enrolled. Sixty-nine patients in IIST-UCB group were treated with ATG + CsA + CTX combined with cord blood, while 54 patients in IST group with ATG + CsA. The overall remission rates (ORRs), complete remission (CR) rates and partial response (PR) rates of IIST-UCB group and IST group at 3 months were 69.67% vs 51.85% (P = .045), 21.74% vs 3.7% (P = .004) and 47.83% vs 48.15% (P = .972), respectively. After 6 months of treatment, they were 76.81% vs 57.41% (P = .022), 37.68% vs 11.11% (P = .001) and 39.13% vs 46.30% (P = .425), respectively. After 1 year of treatment, they were 85.51% vs 61.11% (P = .002), 59.42% vs 25.93% (P = .000) and 26.09% vs 35.19% (P = .275), respectively. The ORRs and CR rates of IIST-UCB group were both significantly higher than IST group after 3 months, 6 months and 1 year of treatment. The neutrophil granulocyte, platelet and haemoglobin recovery times of IIST-UCB group were significantly shorter than IST group. Compared with standard IST, IIST-UCB as an effective therapy for SAA patients without HLA-identical donors accelerated the haematopoietic reconstitution, resulting in higher early CR rates.

Human Umbilical Cord Blood Infusions in the Management of Autism Spectrum Disorder.

Objective: To provide an overview of the role of umbilical cord blood (UCB) in managing autism spectrum disorder (ASD) symptoms in children aged 4-8 years.Data Sources: A systematic literature search was conducted using the terms (autism OR autism spectrum disorder AND umbilical cord blood infusion UCB OR umbilical cord blood). The review was limited to articles published in the English language from 1945 to September 2020. The database search included PubMed, Scopus, and EMBASE.Study Selection: The initial search revealed 165 hits of potential relevance.Data Extraction: The articles were analyzed to obtain clinical information relevant to meeting the review objectives.Data Synthesis: After title, abstract, and full article review, 3 UCB studies were selected for analysis.Results: The systematic review showed mixed results. In the first study, improvements were seen in the socialization and communication domains and adaptive behavior with UCB infusion. The Pervasive Developmental Disorder Behavior Inventory composite T score and Expressive One-Word Picture Vocabulary Test (EOWPVT) score also improved. Symptomatic improvement was seen in half of the patients. The second study showed no improvement in the EOWPVT, Receptive One-Word Picture Vocabulary Test, Clinical Global Impressions scale, or Vineland Adaptive Behavior Scales (VABS), second edition. The third study showed nonsignificant improvement in the VABS, third edition socialization scale scores; however, major improvement in the communication domain was seen for those with nonverbal IQ ≥ 70. No serious adverse events were reported in any of the studies.Conclusion: Few studies have evaluated the role of UCB infusion in addressing symptoms of ASD. Due to the limited number of studies, more research is warranted.

Expanded Access Protocol of Umbilical Cord Blood Infusion for Children with Neurological Conditions: An Update.

Expanded Access Protocol of Umbilical Cord Blood Infusion for Children with Neurological Conditions: An Update.

First case of low-dose umbilical cord blood therapy for pediatric acute respiratory distress syndrome induced by Pneumocystis carinii pneumonia

ObjectiveThis study aimed to present the case of a boy with acute distress syndrome (ARDS) treated with low-dose umbilical cord blood (UCB) therapy and explore the underlying possible mechanism.MethodsA 7-year-old boy with severe Pneumocystis carinii pneumonia and severe ARDS was treated with allogeneic UCB as salvage therapy.ResultsThe patient did not improve after being treated with lung protective ventilation, pulmonary surfactant replacement, and extracorporeal membrane oxygenation (ECMO) for 30 days. However, his disease reversed 5 days after allogeneic UCB infusion, and he weaned from ECMO after 7 days of infusion. Bioinformatics confirmed that his Toll-like receptor (TLR) was abnormal before UCB infusion. However, after the infusion, his immune system was activated and repaired, and the TLR4/MyD88/NF-κB signaling pathway was recovered.ConclusionAllogenic UCB could treat ARDS by repairing the TLR4/MyD88/NF-κB signaling pathway, thereby achieving stability of the immune system.

Human umbilical cord blood infusions in management of autism spectrum disorder: Narrative review

IntroductionAccording to CDC’s Autism and Developmental Disabilities Monitoring Network surveillance in 2016, autism spectrum disorder (ASD) was prevalent in 1 in 54 children in 11 states of the US.ObjectivesThis systematic review provides an overview of Umbilical Cord Blood Infusion (UCB) to decrease symptoms severity in children with (ASD).MethodsSystematic literature search was conducted using “Autism” OR “Autism spectrum disorder” AND “Autologous Umbilical Cord Blood Infusion (AUCBI)” OR “umbilical cord blood” OR “Allogeneic Cord Blood” in PubMed, Embase, and PsycINFO. Three studies were qualified on AUCBI.ResultsWe found 3 studies on UCBI The UCB Infusion phase-I/ open-label trial showed significant improvement in cognitive and behavior scales, especially in the social domain in the first six months, and was more significant in children with higher baseline nonverbal intelligence quotients. Other study/phase II trial failed to show any effects of UCBI on social communication, vocabulary, and other autism symptoms. On subgroup analysis, the improvement in Clinical Global Impression - Improvement (CGI-I) in children without intellectual disability (ID) with the allogenic (not autologous) UCBI was observed. Another randomized, blinded crossover trial failed to show any difference between improvements in CGI baseline severity scores in placebo vs. cord blood infusion groups.ConclusionsThe data provides evidence to support the efficacy and safety of autologous UCBI in symptom severity reductions and improved clinical outcomes without intellectual disability. However, the evidence is inadequate and future large scale clinical are required.

Potentiation of cord blood cell therapy with erythropoietin for children with CP: a 2\u2009\xd7\u20092 factorial randomized placebo-controlled trial

BackgroundConcomitant administration of allogeneic umbilical cord blood (UCB) infusion and erythropoietin (EPO) showed therapeutic efficacy in children with cerebral palsy (CP). However, no clinical studies have investigated the effects of UCB and EPO combination therapy using a 2 × 2 four-arm factorial blinded design with four arms. This randomized placebo-controlled trial aimed to identify the synergistic and individual efficacies of UCB cell and EPO for the treatment of CP.MethodsChildren diagnosed with CP were randomly segregated into four groups: (A) UCB+EPO, (B) UCB+placebo EPO, (C) placebo UCB+EPO, and (D) placebo UCB+placebo EPO. Based on the UCB unit selection criteria of matching for ≥ 4/6 of human leukocyte antigen (HLA)-A, -B, and DRB1 and total nucleated cell (TNC) number of ≥ 3 × 107/kg, allogeneic UCB was intravenously infused and 500 IU/kg human recombinant EPO was administered six times. Functional measurements, brain imaging studies, and electroencephalography were performed from baseline until 12 months post-treatment. Furthermore, adverse events were closely monitored.ResultsEighty-eight of 92 children enrolled (3.05 ± 1.22 years) completed the study. Change in gross motor performance measure (GMPM) was greater in group A than in group D at 1 month (△2.30 vs. △0.71, P = 0.025) and 12 months (△6.85 vs. △2.34, P = 0.018) post-treatment. GMPM change ratios were calculated to adjust motor function at the baseline. Group A showed a larger improvement in the GMPM change ratio at 1 month and 12 months post-treatment than group D. At 12 months post-treatment, the GMPM change ratios were in the order of groups A, B, C, and D. These results indicate synergistic effect of UCB and EPO combination better than each single therapy. In diffusion tensor imaging, the change ratio of fractional anisotropy at spinothalamic radiation was higher in group A than group D in subgroup of age ≥ 3 years. Additionally, higher TNC and more HLA-matched UCB units led to better gross motor outcomes in group A. Adverse events remained unchanged upon UCB or EPO administration.ConclusionsThese results indicate that the efficacy of allogeneic UCB cell could be potentiated by EPO for neurological recovery in children with CP without harmful effects.Trial registrationClinicalTrials.gov, NCT01991145, registered 25 November 2013.

Cord Blood Connect: The International Congress for Cord Blood and Perinatal Tissue Research 2020.

The proceedings contain 15 papers The topics discussed include: targeting neuroinflammation with human umbilical cord tissue-derived mesenchymal stromal cells;multiple doses of umbilical cord blood cells improve long-term perinatal brain injury;COVID-19 and its impact on collection and processing of cord blood units at the Cleveland Cord Blood Center;hydrocortisone-treated DUOC-01, a cord blood-derived cell therapy product, ameliorates experimental autoimmune encephalomyelitis;measuring microglial suppression with multiple assays;impact of donor age on outcomes in hematopoietic stem cell transplantation;single UM171-expanded cord blood transplants support robust T-cell reconstitution with low rates of severe infections;autologous umbilical cord blood-derived cell administration in extreme preterm infants: CORD-SAFE study;and umbilical cord blood infusion reactions

Measuring robustness of brain networks in autism spectrum disorder with Ricci curvature

Ollivier–Ricci curvature is a method for measuring the robustness of connections in a network. In this work, we use curvature to measure changes in robustness of brain networks in children with autism spectrum disorder (ASD). In an open label clinical trials, participants with ASD were administered a single infusion of autologous umbilical cord blood and, as part of their clinical outcome measures, were imaged with diffusion MRI before and after the infusion. By using Ricci curvature to measure changes in robustness, we quantified both local and global changes in the brain networks and their potential relationship with the infusion. Our results find changes in the curvature of the connections between regions associated with ASD that were not detected via traditional brain network analysis.

307 Safety and clinical effects of systemic allogeneic UCB-MSCs therapy for patients with RDEB

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a severe genodermatosis caused by mutations in COL7A1 and characterized by mucocutaneous blistering after minor trauma. Bone marrow–mesenchymal stromal cells (MSCs) have shown therapeutic potential for RDEB patients. Recent preclinical study demonstrated that a systemic infusion of human umbilical cord blood (UCB)-derived nonhematopoietic stem cells correct RDEB murine model. In this study, we wanted to determine the safety and possible clinical efficacy of systemic allogeneic UCB-MSCs therapy for RDEB patients.

A Phase II Randomized Clinical Trial of the Safety and Efficacy of Intravenous Umbilical Cord Blood Infusion for Treatment of Children with Autism Spectrum Disorder

To evaluate whether umbilical cord blood (CB) infusion is safe and associated with improved social and communication abilities in children with autism spectrum disorder (ASD). This prospective, randomized, placebo-controlled, double-blind study included 180 children with ASD, aged 2-7years, who received a single intravenous autologous (n=56) or allogeneic (n=63) CB infusion vs placebo (n=61) and were evaluated at 6months postinfusion. CB infusion was safe and well tolerated. Analysis of the entire sample showed no evidence that CB was associated with improvements in the primary outcome, social communication (Vineland Adaptive Behavior Scales-3 [VABS-3] Socialization Domain), or the secondary outcomes, autism symptoms (Pervasive Developmental Disorder Behavior Inventory) and vocabulary (Expressive One-Word Picture Vocabulary Test). There was also no overall evidence of differential effects by type of CB infused. In a subanalysis of children without intellectual disability (ID), allogeneic, but not autologous, CB was associated with improvement in a larger percentage of children on the clinician-rated Clinical Global Impression-Improvement scale, but the OR for improvement was not significant. Children without ID treated with CB showed significant improvements in communication skills (VABS-3 Communication Domain), and exploratory measures including attention to toys and sustained attention (eye-tracking) and increased alpha and beta electroencephalographic power. Overall, a single infusion of CB was not associated with improved socialization skills or reduced autism symptoms. More research is warranted to determine whether CB infusion is an effective treatment for some children with ASD.

Expanded Access Protocol of Umbilical Cord Blood Infusion for Children with Neurological Conditions

Introduction An expanded access protocol (EAP) of autologous or sibling umbilical cord blood (CB) infusion was established in 2017 under Investigational New Drug #15949 to provide access to this investigational procedure for individuals with certain neurological conditions who do not qualify for available clinical trials. Objective The objective was to report updated enrollment and safety data from a single center EAP of autologous/sibling CB infusion for children with acquired neurological conditions. Methods Children with autism, cerebral palsy, and other related conditions were screened remotely under a separate institutional review board-approved screening protocol, including review of parental questionnaires, medical records, basic labs, and CB unit reports. Based on emerging clinical trial data, the minimum cell dose was increased to a total nucleated cell count (TNCC) >2.0 × 107/kg. CB units also had to have viability >70%, negative sterility cultures and maternal donor screening labs, and a segment available for identity confirmation and potency testing, and sibling units had to be at least human leukocyte antigen-haploidentical. CB units were thawed, washed, and infused via peripheral IV after premedication with IV diphenhydramine and methylprednisolone. Some children received repeated doses, when the TNCC allowed. Results A total of 2,001 children were screened from November 2017 to June 2021, and 464 children received 494 CB infusions under the EAP, including 20 children who had previously participated in a clinical trial and elected to return to receive a subsequent infusion. Due to COVID restrictions, enrollment was suspended for 18 weeks (March 11, 2020, to July 21, 2020). Patient and CB characteristics are shown in Table 1. Infusions were generally well-tolerated. Forty-one (9%) adverse events, all hypersensitivity reactions, were probably or definitely related to CB infusion. Serious adverse events were documented in 8 children, all expected and unrelated to CB infusion. There were 6 (0.01%) positive post-thaw cultures;none developed infections or required antibiotics. Parental surveys were completed 1 year (n = 244, 72%) and 2 years (n = 105, 51%) post-infusion. Parental assessment varied regarding clinical improvement. Discussion Autologous/sibling CB infusions conducted under an EAP for children with neurological conditions are safe and feasible with varied reported responses to the infusions. CB eligibility was amended to incorporate early phase clinical trial outcomes regarding cell dose. Efficacy continues to be evaluated in ongoing clinical trials.

Low-dose decitabine priming with intermediate-dose cytarabine followed by umbilical cord blood infusion as consolidation therapy for elderly patients with acute myeloid leukemia: a phase II single-arm study

BackgroundTreatment of acute myeloid leukemia (AML) in elderly patients remains a great challenge. In this prospective single arm study (ChiCTR-OPC-15006492), we evaluated the efficacy and safety of a novel consolidation therapy with low-dose decitabine (LD-DAC) priming with intermediate-dose cytarabine (ID-Ara-C) followed by umbilical cord blood (UCB) infusion in elderly patients with AML.MethodsA total of 25 patients with a median age of 64-years-old (60–74-years-old) who achieved complete remission (CR) after induction chemotherapy were enrolled in the study.ResultsThe 2-year actual overall survival (OS) rate and leukemia-free survival (LFS) was 68.0 and 60.0%, respectively. The hematological and non-hematological toxicity were mild to moderate, and only one patient died in remission due to infection with possible acute graft versus host disease (aGVHD). Compared to a concurrent cohort of patients receiving conventional consolidation therapy, the study group tended to have an improved OS and LFS (p = 0.046 and 0.057, respectively), while the toxicity was comparable between the two groups.ConclusionsThis study suggested the novel combination of LD-DAC, ID-Ara-C, and UCB infusion might be an optimal consolidation therapy for elderly patients with AML, and a prospective phase III randomized study is warranted to confirm this observation.Trial registrationThis single-arm phase II clinical trial in elderly AML patients was registered prospectively at www.chictr.org.cn (identifier: ChiCTR-OPC-15006492) on June 2, 2015.

Efficacy analysis of haploidentical allogeneic hematopoietic stem cell transplantation combined with third-party umbilical cord blood infusion in treatment of high-risk lymphoblastic malignancies

Objective To evaluate the efficacy of haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HSCT) combined with third-party umbilical cord blood (UCB) infusion in treatment of high-risk lymphoblastic malignancies. Methods The clinical data of 20 patients with high-risk lymphoblastic malignancies who received Haplo-HSCT from April 2012 to April 2015 in Shanghai General Hospital were retrospectively analyzed, which were compared with the data from 15 patients who underwent matched unrelated donor HSCT (MUD-HSCT) or 14 matched sibling donor HSCT (MSD-HSCT) during the same period. The efficacy of Haplo-HSCT combined with UCB infusion in treatment of high-risk lymphoblastic malignancies was evaluated. The preparative regimen mainly consisted of teniposide, cyclophosphamide and total body irradiation (TBI). Graft versus host disease (GVHD) preparative regimen included cyclosporine and a short term of methotrexate. The patients who received Haplo-HSCT combined with UCB infusion and MUD-HSCT were treated with antithymocyte globulin (ATG). Results After the transplantation, one patient in MUD-HSCT group and one in MSD-HSCT group died within 21 days, and other patients were engrafted successfully. The median time of neutrophil engraftment was 13 days (10-18 d), 12 days (9-16 d) and 12 days (9-14 d) in Haplo-HSCT + UCB group, MUD-HSCT group and MSD-HSCT group, respectively; the median time of platelets engraftment was 11 days (9-18 d), 12 days (10-23 d) and 12 days (9-14 d), respectively. There were 10, 3, 3 cases of grade Ⅱ-Ⅳ acute GVHD at day 100 in the three groups, respectively, and there were 6, 4, 3 cases of chronic GVHD in the three groups, respectively. The 2-year cumulative incidence of relapse was 40.6%, 66.2% and 26.7%, respectively. The predicted 2-year overall survival rate was 37.9%, 42.9% and 55.4%, respectively. All these data had no significant difference (all P > 0.05). Conclusion The efficacy of Haplo-HSCT combined with UCB infusion is similar to that of MUD-HSCT or MSD-HSCT in treatment of high-risk lymphoblastic malignancies, which should be recommended to the patients with high-risk lymphoblastic malignancies and without matched donors. Key words: Lymphoblastic malignancies; Allogeneic hematopoietic stem cell transplantation; Fetal blood

Dickkopf-1 Treatment Stimulates Hematopoietic Regenerative Function in Infused Endothelial Progenitor Cells.

Acute high-dose radiation injury damages the bone marrow hematopoietic stem and progenitor cell compartment. This damage compromises the functional ability of the bone marrow to produce mature blood cells and results in an increased risk of death due to hematopoietic complications. Past work has shown that the bone marrow endothelium provides critical cues, which promote hematopoietic stem cell regeneration after injury. Additionally, transfusion of endothelial cells after radiation injury has been shown to promote recovery of both the bone marrow vasculature and hematopoietic systems. In this work, we examined the regenerative capacity of intravenous infusion of umbilical cord-blood derived endothelial progenitor cells (EPCs) since this is a cell source which is easy to obtain, expand and cryopreserve. We show that pre-treatment with the Wnt-antagonist Dickkopf1 (Dkk1) augments EPC regenerative function in an allogeneic mouse transplant model. Here, hematopoietic recovery was assessed in Balb/c mice after 5 Gy total-body irradiation and transplantation with C57/BL6-derived EPCs either with or without Dkk1 pre-treatment. The Dkk1-treated EPC group had significantly faster recovery of peripheral white blood cells, total bone marrow cellularity, bone marrow progenitors and BM endothelial cells compared to EPC treatment alone or saline controls. Importantly, after an LD50/30 dose of 8 Gy in the Balb/c mouse, Dkk1-treated EPCs were able to rescue 100% of irradiated mice versus 80% in the EPC control group and only 33% in the saline-treated group. To understand how Dkk1 induces regenerative function in the EPCs, we screened for pro-regenerative factors secreted by the EPC in response to Dkk1. Dkk1-treated EPCs were observed to secrete high levels of the anti-fibrotic protein follistatin as well as several proteins known to promote regeneration including EGF, VEGF and G-CSF. This work demonstrates the potential for Dkk1-treated EPCs as a rescue therapeutic for victims of acute radiation injury.

Safety of Autologous Cord Blood Cells for Preterms: A Descriptive Study.

Background Preterm birth complications are one of the leading causes of death among children under 5 years of age. Despite advances in medical care, many survivors face a lifetime of disability, including mental and physical retardation, and chronic lung disease. More recently, both allogenic and autogenic cord blood cells have been applied in the treatment of neonatal conditions such as hypoxic-ischemic encephalopathy (HIE) and bronchopulmonary dysplasia (BPD). Objective To assess the safety of autologous, volume- and red blood cell- (RBC-) reduced, noncryopreserved umbilical cord blood (UCB) cell infusion to preterm infants. Method This study was a phase I, open-label, single-arm, single-center trial to evaluate the safety of autologous, volume- and RBC-reduced, noncryopreserved UCB cell (5 × 107cells/kg) infusion for preterm infants <37 weeks gestational age. UCB cell characteristics, pre- and postinfusion vital signs, and laboratory investigations were recorded. Clinical data including mortality rates and preterm complications were recorded. Results After processing, (22.67 ± 4.05) ml UCB cells in volume, (2.67 ± 2.00) × 108 cells in number, with (22.67 ± 4.05) × 106 CD34+, (3.72 ± 3.25) × 105 colony forming cells (CFU-GM), and (99.7 ± 0.17%) vitality were infused to 15 preterm infants within 8 hours after birth. No adverse effects were noticed during treatment. All fifteen patients who received UCB infusion survived. The duration of hospitalization ranged from 4 to 65 (30 ± 23.6) days. Regarding preterm complications, no BPD, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP) was observed. There were 1/15 (7%) infant with intraventricular hemorrhage (IVH), 5/15 (33.3%) infants with ventilation-associated pneumonia, and 10/15 (66.67%) with anemia, respectively. Conclusions Collection, preparation, and infusion of fresh autologous UCB cells to preterm infants is feasible and safe. Adequately powered randomized controlled studies are needed.