Supplemental Video for Stover AE, Brick DJ, Nethercott HE, Banuelos MG, Sun L, O’Dowd DK, Schwartz PH. Process-based expansion and neural differentiation of human pluripotent stem cells for transplantation and disease modeling. J Neurosci Res. 2013 Oct;91(10):1247-62.
J Virol. 2013 Oct;87(20):10968-79. doi: 10.1128/JVI.01120-13. Epub 2013 Jul 31.
Later passages of neural progenitor cells from neonatal brain are more permissive for human cytomegalovirus infection.
Pan X1, Li XJ, Liu XJ, Yuan H, Li JF, Duan YL, Ye HQ, Fu YR, Qiao GH, Wu CC, Yang B, Tian XH, Hu KH, Miao LF, Chen XL, Zheng J, Rayner S, Schwartz PH, Britt WJ, Xu J, Luo MH.
Congenital human cytomegalovirus (HCMV) infection is the most frequent infectious cause of birth defects, primarily neurological disorders. Neural progenitor/stem cells (NPCs) are the major cell type in the subventricular zone and are susceptible to HCMV infection. In culture, the differentiation status of NPCs may change with passage, which in turn may alter susceptibility to virus infection. Previously, only early-passage (i.e., prior to passage 9) NPCs were studied and shown to be permissive to HCMV infection. In this study, NPC cultures derived at different gestational ages were evaluated after short (passages 3 to 6) and extended (passages 11 to 20) in vitro passages for biological and virological parameters (i.e., cell morphology, expression of NPC markers and HCMV receptors, viral entry efficiency, viral gene expression, virus-induced cytopathic effect, and release of infectious progeny). These parameters were not significantly influenced by the gestational age of the source tissues. However, extended-passage cultures showed evidence of initiation of differentiation, increased viral entry, and more efficient production of infectious progeny. These results confirm that NPCs are fully permissive for HCMV infection and that extended-passage NPCs initiate differentiation and are more permissive for HCMV infection. Later-passage NPCs being differentiated and more permissive for HCMV infection suggest that HCMV infection in fetal brain may cause more neural cell loss and give rise to severe neurological disabilities with advancing brain development.
J Inherit Metab Dis. 2014 Mar 12. [Epub ahead of print]
Effects of hematopoietic stem cell transplantation on acyl-CoA oxidase deficiency: a sibling comparison study.
Wang RY1, Monuki ES, Powers J, Schwartz PH, Watkins PA, Shi Y, Moser A, Shrier DA, Waterham HR, Nugent DJ, Abdenur JE.
OBJECTIVE: Acyl-CoA oxidase (ACOX1) deficiency is a rare disorder of peroxisomal very-long chain fatty acid oxidation. No reports detailing attempted treatment, longitudinal imaging, or neuropathology exist. We describe the natural history of clinical symptoms and brain imaging in two siblings with ACOX1 deficiency, including the younger sibling’s response to allogeneic unrelated donor hematopoietic stem cell transplantation (HSCT).
METHODS: We conducted retrospective chart review to obtain clinical history, neuro-imaging, and neuropathology data. ACOX1 genotyping were performed to confirm the disease. In vitro fibroblast and neural stem cell fatty acid oxidation assays were also performed.
RESULTS: Both patients experienced a fatal neurodegenerative course, with late-stage cerebellar and cerebral gray matter atrophy. Serial brain magnetic resonance imaging in the younger sibling indicated demyelination began in the medulla and progressed rostrally to include the white matter of the cerebellum, pons, midbrain, and eventually subcortical white matter. The successfully engrafted younger sibling had less brain inflammation, cortical atrophy, and neuronal loss on neuro-imaging and neuropathology compared to the untreated older sister. Fibroblasts and stem cells demonstrated deficient very long chain fatty acid oxidation.
INTERPRETATION: Although HSCT did not halt the course of ACOX1 deficiency, it reduced the extent of white matter inflammation in the brain. Demyelination continued because of ongoing neuronal loss, which may be due to inability of transplant to prevent progression of gray matter disease, adverse effects of chronic corticosteroid use to control graft-versus-host disease, or intervention occurring beyond a critical point for therapeutic efficacy.
Recently Dr. Schwartz went to UC Davis and presented the work his group is doing on MPSI. This work is currently supported by CIRM. His talk was well received.
Dr. Schwartz’s group will be presenting current findings in autism in San Diego. Emphasis will be on the bioinformatic approaches he is currently undertaking.
Pediatrics 2040 event where Dr. Schwartz will be a speaker:
Friday October 4th 2013
11:00 am – Regenerative Medicine and Stem Cells – Moderator: Phillip Schwartz, PhD
Overview: Stem Cell Therapy
– Phillip Schwartz, PhD
Ethical considerations/Sources of cells/GMP Issues and problems associated with tumorigenicity and immunogenicity.