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  • 1
    Online Resource
    Online Resource
    Nonhematopoietic Umbilical Cord Blood Stem Cell Administration Improves Long-term Neurodevelopment After Periventricular-Intraventricular Hemorrhage in Neonatal Rats
    SAGE Publications ; 2023
    In:  Cell Transplantation Vol. 32 ( 2023-01)
    Details
    In: Cell Transplantation, SAGE Publications, Vol. 32 ( 2023-01)
    Abstract: Periventricular-intraventricular hemorrhage (PIVH) is common in extremely low gestational age neonates (ELGAN) and leads to motor and behavioral impairments. Currently there is no effective treatment for PIVH. Whether human nonhematopoietic umbilical cord blood-derived stem cell (nh-UCBSC) administration reduces the severity of brain injury and improves long-term motor and behavioral function was tested in an ELGAN-equivalent neonatal rat model of PIVH. In a collagenase-induced unilateral PIVH on postnatal day (P) 2 model, rat pups received a single dose of nh-UCBSCs at a dose of 1 × 10 6 cells i.p. on P6 (PIVH + UCBSC group) or were left untreated (Untreated PIVH group). Motor deficit was determined using forelimb placement, edge-push, and elevated body swing tests at 2 months ( N = 5–8). Behavior was evaluated using open field exploration and rearing tests at 4 months ( N =10–12). Cavity volume and hemispheric volume loss on the PIVH side were determined at 7 months ( N = 6–7). Outcomes were compared between the Untreated PIVH and PIVH + UCBSC groups and a Control group. Unilateral motor deficits were present in 60%–100% of rats in the Untreated PIVH group and 12.5% rats in the PIVH + UCBSC group ( P = 0.02). Untreated PIVH group exhibited a higher number of quadrant crossings in open field exploration, indicating low emotionality and poor habituation, and had a cavitary lesion and hemispheric volume loss on the PIVH side. Performance in open field exploration correlated with cavity volume ( r 2 = 0.25; P 〈 0.05). Compared with the Untreated PIVH group, performance in open field exploration was better ( P = 0.0025) and hemispheric volume loss was lower (19.9 ± 4.4% vs 6.1 ± 2.6%, P = 0.018) in the PIVH + UCBSC group. These results suggest that a single dose of nh-UCBSCs administered in the subacute period after PIVH reduces the severity of injury and improves neurodevelopment in neonatal rats.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    URL: Article
    DOI: 10.1177/09636897231189301
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2020466-8
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  • 2
    Online Resource
    Online Resource
    Interspecies Organogenesis for Human Transplantation
    SAGE Publications ; 2019
    In:  Cell Transplantation Vol. 28, No. 9-10 ( 2019-09), p. 1091-1105
    Details
    In: Cell Transplantation, SAGE Publications, Vol. 28, No. 9-10 ( 2019-09), p. 1091-1105
    Abstract: Blastocyst complementation combined with gene editing is an emerging approach in the field of regenerative medicine that could potentially solve the worldwide problem of organ shortages for transplantation. In theory, blastocyst complementation can generate fully functional human organs or tissues, grown within genetically engineered livestock animals. Targeted deletion of a specific gene(s) using gene editing to cause deficiencies in organ development can open a niche for human stem cells to occupy, thus generating human tissues. Within this review, we will focus on the pancreas, liver, heart, kidney, lung, and skeletal muscle, as well as cells of the immune and nervous systems. Within each of these organ systems, we identify and discuss (i) the common causes of organ failure; (ii) the current state of regenerative therapies; and (iii) the candidate genes to knockout and enable specific exogenous organ development via the use of blastocyst complementation. We also highlight some of the current barriers limiting the success of blastocyst complementation.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    URL: Article
    DOI: 10.1177/0963689719845351
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
    detail.hit.zdb_id: 2020466-8
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  • 3
    Online Resource
    Online Resource
    Immunomodulation with Human Umbilical Cord Blood Stem Cells Ameliorates Ischemic Brain Injury – A Brain Transcriptome Profiling Analysis
    SAGE Publications ; 2019
    In:  Cell Transplantation Vol. 28, No. 7 ( 2019-07), p. 864-873
    Details
    In: Cell Transplantation, SAGE Publications, Vol. 28, No. 7 ( 2019-07), p. 864-873
    Abstract: Our group previously demonstrated that administration of a CD34-negative fraction of human non- hematopoietic umbilical cord blood stem cells (UCBSC) 48 h after ischemic injury could reduce infarct volume by 50% as well as significantly ameliorate neurological deficits. In the present study, we explored possible mechanisms of action using next generation RNA sequencing to analyze the brain transcriptome profiles in rats with ischemic brain injury following UCBSC therapy. Two days after ischemic injury, rats were treated with UCBSC. Five days after administration, total brain mRNA was then extracted for RNAseq analysis using Illumina Hiseq 2000. We found 275 genes that were significantly differentially expressed after ischemic injury compared with control brains. Following UCBSC treatment, 220 of the 275 differentially expressed genes returned to normal levels. Detailed analysis of these altered transcripts revealed that the vast majority were associated with activation of the immune system following cerebral ischemia which were normalized following UCBSC therapy. Major alterations in gene expression profiles after ischemia include blood-brain-barrier breakdown, cytokine production, and immune cell infiltration. These results suggest that UCBSC protect the brain following ischemic injury by down regulating the aberrant activation of innate and adaptive immune responses.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    URL: Article
    DOI: 10.1177/0963689719836763
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
    detail.hit.zdb_id: 2020466-8
    Location Call Number Limitation Availability
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