Therapeutic potentials of human embryonic stem cells in Parkinson's disease.

The loss of dopaminergic neurons of the substantia nigra is the pathological hallmark characteristic of Parkinson's disease (PD). The strategy of replacing these degenerating neurons with other cells that produce dopamine has been the main approach in the cell transplantation field for PD research. The isolation, differentiation, and long-term cultivation of human embryonic stem cells and the therapeutic research discovery made in relation to the beneficial properties of neurotrophic and neural growth factors has advanced the transplantation field beyond dopamine-producing cells.

TNF-alpha knockout and minocycline treatment attenuates blood-brain barrier leakage in MPTP-treated mice.

Following intraparenchymal injection of the dopamine (DA) neurotoxin 6-hydroxydopamine, we previously demonstrated passage of fluoresceinisothiocyanate-labeled albumin (FITC-LA) from blood into the substantia nigra (SN) and striatum suggesting damage to the blood-brain barrier (BBB). The factors contributing to the BBB leakage could have included neuroinflammation, loss of DA neuron control of barrier function, or a combination of both. In order to determine which factor(s) was responsible, we assessed BBB integrity using the FITC-LA technique in wild-type (WT), tumor necrosis factor alpha (TNF-alpha) knockout (KO), and minocycline (an inhibitor of microglia activation) treated mice 72 h following treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Cytokines produced by cultured human umbilical cord blood (HUCB) cells: implications for brain repair.

The potential therapeutic benefits from human umbilical cord blood (HUCB) cells for the treatment of injuries, diseases, and neurodegeneration are becoming increasingly recognized. The transplantation or infusion of cord blood cells in various animal models, such as ischemia/stroke, traumatic brain injury, myocardial infarction, Parkinson's disease, and amyotropic lateral sclerosis, has resulted in amelioration of behavioral deficits, and with some diseases, a prolonged lifespan decreased neuropathology. Previously, we reported the migration of HUCB cells to ischemic brain supernatant (tissue extracts) is time-dependent, and the expression of specific chemokines responds to this migration pattern.

Progressive dopamine neuron loss in Parkinson's disease: the multiple hit hypothesis.

Animal models have been an essential tool for researchers and clinicians in their efforts to study and treat Parkinson's disease (PD). Thus, the various ways 6-hydroxydopamine is employed, the use of MPTP in rodents and nonhuman primates, the prenatal exposure to bacterial endotoxin, the postnatal exposure to environmental toxins such as paraquat and rotenone, the assessment of dopamine (DA) neurons in genetic knockout mouse, and even the behavioral analysis of fruit flies and worms have added significantly to our knowledge base of PD--or have they? Are these animal models manifesting a true model of PD? Have the 7786 published studies (to date) on PD with animal models led to a clearer understanding of its etiology, treatment, or progression? In this review we critically assess this question. We begin with a succinct history of the major contributions, which have led to the current animal models of PD.

Stroke-induced migration of human umbilical cord blood cells: time course and cytokines.

The therapeutic window for treatment of individuals after stroke is narrow, regardless of the treatment regime; extension of this window would provide a major therapeutic advance. In prior reports, we demonstrated significant improvements in the behavioral defects of rats that received human umbilical cord blood (HUCB) cells 24 h after a middle cerebral arterial occlusion. These effects paralleled the recruitment of these cells to the site of tissue damage.

Use of human umbilical cord blood (HUCB) cells to repair the damaged brain.

Neurodegenerative diseases as well as acute center nervous system (CNS) injuries remains a problematic and frustrating area of medicine in terms of treatments and cures, which is mostly due to the complex circuitry of the CNS along with our limited knowledge. Therapeutically, the last two and a half decades have offered new hope for those suffering from neurodegenerative diseases or injuries with advent of new drug discoveries and cellular therapies. Cell transplantation is a compelling and potential treatment for certain neurological and neurodegenerative diseases as well as for acute injuries to the spinal cord and brain.

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.

Transplantation of human umbilical cord blood cells in the repair of CNS diseases.

Cell transplantation therapies have been used to treat certain neurodegenerative diseases such as Parkinson's and Huntington's disease. However, ethical concerns over the use of fetal tissues, and the inherent complexities of standardising the procurement, processing and transplantation methods of this tissue, have prompted the search for a source of cells that have less ethical stigmatisations, are readily available and can be easily standardised. Several sources of human cells that meet these principles have been under investigation.

Human umbilical cord blood (HUCB) cells for central nervous system repair.

Cellular therapy is a compelling and potential treatment for certain neurological and neurodegenerative diseases as well as a viable treatment for acute injury to the spinal cord and brain. The hematopoietic system offers alternative sources for stem cells compared to those of fetal or embryonic origin. Bone marrow stromal and umbilical cord cells have been used in pre-clinical models of brain injury, directed to differentiate into neural phenotypes, and have been related to functional recovery after engraftment in central nervous system (CNS) injury models.

Nicotinic acetylcholine receptors on NT2 precursor cells and hNT (NT2-N) neurons.

This is the first report, to our knowledge, of prominent, natural expression of nAChR alpha4, alpha6 and alpha9 subunits in a human, neuronally-committed cell line. We performed studies with specific reference to the expression of nicotinic acetylcholine receptors (nAChR) to further characterize a human, postmitotic, transplantable, with a neuronal phenotype, cell line called hNT (also called NT2-N). hNT cells acquire a distinctive neuronal phenotype upon differentiation from their NT2 precursors.

Nicotine's oxidative and antioxidant properties in CNS.

Nicotine has been reported to be therapeutic in some patients with certain neurodegenerative diseases and to have neuroprotective effects in the central nervous system. However, nicotine administration may result in oxidative stress by inducing the generation of reactive oxygen species in the periphery and central nervous system. There is also evidence suggesting that nicotine may have antioxidant properties in the central nervous system.

Human umbilical cord blood cells express neural antigens after transplantation into the developing rat brain.

Recently, our laboratory began to characterize the mononuclear cells from human umbilical cord blood (HUCB) both in vitro and in vivo. These cryopreserved human cells are available in unlimited quantities and it is believed that they may represent a source of cells with possible therapeutic and practical value. Our previous molecular and immunocytochemical studies on cultured HUCB cells revealed their ability to respond to nerve growth factor (NGF) by increased expression of neural markers typical for nervous system-derived stem cells.

Anxiolytic effects of mecamylamine in two animal models of anxiety.

Clinical and preclinical evidence suggests that mecamylamine, a nicotinic receptor antagonist, may have anxiolytic properties. The purpose of this study was to further investigate the anxiolytic properties of mecamylamine in rats as measured by the Elevated Plus Maze and the Social Interaction models of anxiety and to determine if manipulation of the testing environment (either brightly lit or dimly lit conditions) influenced the results. Results indicated that mecamylamine had significant anxiolytic effects in both the Elevated Plus Maze and Social Interaction Tests and that these effects were dependent on dose administered and the level of anxiety produced under different testing conditions.