Perspectives on the Use of eHealth in the Management of Patients With Schizophrenia.

Mobile devices, digital technologies, and web-based applications-known collectively as eHealth (electronic health)-could improve health care delivery for costly, chronic diseases such as schizophrenia. Pharmacologic and psychosocial therapies represent the primary treatment for individuals with schizophrenia; however, extensive resources are required to support adherence, facilitate continuity of care, and prevent relapse and its sequelae. This paper addresses the use of eHealth in the management of schizophrenia based on a roundtable discussion with a panel of experts, which included psychiatrists, a medical technology innovator, a mental health advocate, a family caregiver, a health policy maker, and a third-party payor. The expert panel discussed the uses, benefits, and limitations of emerging eHealth with the capability to integrate care and extend service accessibility, monitor patient status in real time, enhance medication adherence, and empower patients to take a more active role in managing their disease. In summary, to support this technological future, eHealth requires significant research regarding implementation, patient barriers, policy, and funding.

Multiple transplants of hNT cells into the spinal cord of SOD1 mouse model of familial amyotrophic lateral sclerosis.

hNT cells, derived from a human teratocarcinoma cell line, are versatile neuron-like cells that have been studied as possible treatment vehicles for neurodegenerative diseases. Previously, we showed the postponement of motor deficit symptoms in a G93A mouse model of amyotrophic lateral sclerosis (ALS) by transplanting hNT cells into the lumbar spinal cord. In this study, we examined the engraftment of hNT cells at multiple sites within the lumbar spinal cord by morphological analysis of neuritic process development. Results demonstrated that cells implanted at multiple sites established neuritic processes of different lengths independent of the number of cell implants. The hNT fiber outgrowth was a maximum of 0.15-0.3 mm from the transplants and mostly spread within the gray matter; interconnections between implants were not found. Therefore, we suggest that the observed postponement of motor deficit symptoms in G93A mice was not a result of neuritic outgrowth from the implanted hNT cells.

Human umbilical cord blood progenitors: the potential of these hematopoietic cells to become neural.

The mononuclear fraction from human umbilical cord blood (HUCB) contains a significant number of stem/progenitor cells that in theory could be come any cell in the body, including neurons. Taking into consideration that transdifferentiation would be a very rare event and also knowing that overlapping genetic programs for hematopoiesis and neuropoiesis exist, we undertook a characterization of the HUCB mononuclear fraction, including analysis of cellular subpopulations and their morphology, cell viability, proliferation, and expression of neural and hematopoietic antigens. Two cell populations were apparent-adherent and floating fractions. The adherent fraction was mainly lymphocytes (~53%) expressing hematopoietic antigens. Upon replate, the floating population had many cells that expressed stem cell antigens. More of the cells in this subfraction expressed neural proteins. Neurotrophin receptors trkB and trkC were present in both cell fractions, although expression was higher in the floating fraction. Our initial characterization suggests that a subpopulation of cells exists within the HUCB mononuclear fraction that seems to have the potential to become neural cells, which could then be used in the development of cell-based therapies for brain injuries and diseases.

Neutrophil-specific chemokines are produced by astrocytic cells but not by neuronal cells.

BACKGROUND: Neutrophils have a central role in the inflammatory conditions of the central nervous system (CNS). ELR chemokines direct neutrophil migration, but the source of chemokines in the CNS is unclear. We quantified chemokine production using cell-line models of astrocytic and neuronal cells, specifically NT2.N cells, a human line with characteristics of immature neurons, and NT2.A cells, a line with characteristics of astrocytes. OBJECTIVE: In NT2.N and NT2.A cells, and their parent cell line NT2, we sought to: (1) quantify ELR chemokines, (2) determine receptor (CXCR-1 and CXCR-2) expression, and (3) measure the function of the chemokines generated from these cells. DESIGN/METHODS: NT2 cells were differentiated into NT2.N cells and NT2.A cells with all trans retinoic acid and mitosis inhibitors. Chemokine concentrations in culture supernatants were determined by ELISA. Immunofluorescence was used to detect CXCR-1 and CXCR-2. RT-PCR was used to determine chemokine and chemokine receptor mRNA. Chemotaxis assays were used to assess function. RESULTS: ELR chemokines were not detected in supernatants of NT2 or NT2.N cells, although mRNA for GRO-gamma/CXCL3 was found in both. In contrast, in NT2.A cells, mRNA and protein were present for GCP-2/CXCL6, GRO-alpha/CXCL1, GRO-gamma/CXCL3, and IL-8/CXCL8. CXCR-1 and CXCR-2 were expressed on NT2, NT2.N, and NT2.A cells detected by immunofluorescent staining and RT-PCR. Supernatants of NT2.A cells resulted in neutrophil chemotactic function of 30.5 +/- 3.9%, greater than NT2 cells (12.3 +/- 1.6%, mean +/- SEM, P < 0.01). CONCLUSIONS: We speculate that astrocytes are a source of ELR chemokines in the human CNS and that neurons and astrocytes can respond to those chemokines.

Tumorigenicity issues of embryonic carcinoma-derived stem cells: relevance to surgical trials using NT2 and hNT neural cells.

Cell therapy is a rapidly moving field with new cells, cell lines, and tissue-engineered constructs being developed globally. As these novel cells are further developed for transplantation studies, it is important to understand their safety profiles both prior to and posttransplantation in animals and humans. Embryonic carcinoma-derived cells are considered an important alternative to stem cells. The NTera2/D1 teratocarcinoma cell-line (or NT2-N cells) gives rise to neuron-like cells called hNT neurons after exposure to retinoic acid. NT2 cells form tumors upon transplantation into the rodent. However, when the NT2 cells are treated with retinoic acid to produce hNT cells, they terminally differentiate into post-mitotic neurons with no sign of tumorigenicity. Preliminary human transplantation studies in the brain of stroke patients also demonstrated a lack of tumorigenicity of these cells. This review focuses on the use of hNT neurons in cell transplantation for the treatment in central nervous system (CNS) diseases, disorders, or injuries and on the mechanism involved in retinoic acid exposure, final differentiation state, and subsequent tumorigenicity issues that must be considered prior to widespread clinical use.

The transcription factor Nurr1 in human NT2 cells and hNT neurons.

Human, neuronally committed hNT or NT2-N cells, originally derived from the Ntera2/D1 (NT2) clone after exposure to retinoic acid (RA), represent a potentially important source of cells to treat neurodegenerative diseases. Our previous in vitro experiments showed that hNT cells possess immunocytochemically detectable markers typical of dopaminergic (DA) ventral mesencephalic (VM) neurons, including tyrosine hydroxylase (TH), dopamine transporter (DAT), dopamine receptor (D2), and aldehyde dehydrogenase (AHD-2). In the current study, we sought to examine whether Nurr1, an orphan receptor of the nuclear receptor superfamily shown to be essential for the development, differentiation and survival of midbrain DA neurons, would be expressed in 3, 4, or 5 week RA-induced hNT neurons and their NT2 precursors. Our immunocytochemical analyses indicate that NT2 cells as well as hNT neurons independent of the length of RA-driven differentiation were Nurr1-immunoreactive. RT-PCR analysis confirmed the expression of Nurr1-specific mRNA in both NT2 precursors and the hNT neurons. Furthermore, immunocytochemical co-expression of Nurr1 and TH was detected in hNT neurons. The findings of this study suggest that Nurr1 may be important during the development of hNT neurons and involved in their differentiation into the dopaminergic phenotype.