Membrane properties of neuron-like cells generated from adult human bone-marrow-derived mesenchymal stem cells.

Adult mesenchymal stem cells (MeSCs) isolated from human bone marrow are capable of generating neural stem cell (NSC)-like cells that can be subsequently differentiated into cells expressing molecular markers for neurons. Here we report that these neuron-like cells had functional properties similar to those of brain-derived neurons. Whole-cell patch-clamp recordings and calcium imaging experiments were performed on neuron-like cells differentiated from bone-marrow-derived NSC-like cells.

Phenotypic characteristics of hybrid cells produced by cell fusion of porcine adrenal chromaffin cells with human mesenchymal stem cells: a preliminary study.

Background And Purpose: Transplantation of adrenal chromaffin cells (CCs) that release endogenous opioid peptides and catecholamines produces significant antinociceptive effects in patients with terminal cancer pain. In clinical practice, however, obtaining a sufficient number of chromaffin cells may not be possible because of the limited availability of human adrenal tissue. Recent works have shown that fusion of bone marrow-derived cells with differentiated cells can occur spontaneously in vivo and acquire the phenotype of the recipient cells.

Genetically engineered human mesenchymal stem cells produce met-enkephalin at augmented higher levels in vitro.

We have reported that transplantation of adrenal medullary chromaffin cells that release endogenous opioid peptides into pain modulatory regions in the CNS produce significant antinociceptive effects in patients with terminal cancer pain. However, the usefulness of this procedure is minimal because the availability of human adrenal tissue is very limited. Alternative xenogeneic materials, such as porcine and bovine adrenal chromaffin cells present problems of immune rejection and possible pathogenic contamination.

Recombinant herpes vector-mediated analgesia in a primate model of hyperalgesia.

Some chronic pain syndromes are characterized by episodes of intense burning and hyperalgesia in localized areas of skin. These sensations are thought to be mediated, at least in part, by the activity of damaged, unmyelinated C nociceptors. These phenomena were modeled by assaying responses of macaques to thermal and chemical stimuli that produced periodic activation and sensitization of C nociceptors.

Oxytocin receptors in brain cortical regions are reduced in haploinsufficient (+/-) reeler mice.

Objective: Both oxytocin (OT) and reelin are particularly significant during development and the absence of either may interfere with normal brain development. In addition, reelin is critical to the development of the GABAergic system and GABA modulates the release of OT. Availability of the reelin haploinsufficient (+/-) reeler mouse (HRM) provides a model for examining the role of reelin in the development of the OT system and especially in the expression of the OT receptor (OTR).

Porocytosis: a transient pore array secretes the neurotransmitter packet.

The porocytosis hypothesis is based on the arrayed nature of synaptic vesicles which forms the anatomical functional unit of secretion. The presynaptic array and the postsynaptic array of receptors form a synaptomere which is the unit of transmission. A transient increase in calcium ions, triggered by an action potential, activates all pores of the array to pulse transmitter.

Secretion without membrane fusion: porocytosis.

We have recently proposed a mechanism to describe secretion, a fundamental process in all cells. That hypothesis, called porocytosis, embodies all available data and encompasses both forms of secretion, i.e.

Porcine chromaffin cells, culture, and transplant for antinociceptive effects in rodents and primates.

It has been shown that xenografts and allografts of spinally transplanted adrenal chromaffin cells produce antinociception in animals and pain relief in patients with cancer pain. As there is a very limited availability of human adrenal tissue to serve as allografts, the clinical need for xenogeneic chromaffin cells as transplants is obvious. Bovine adrenal glands as a steady source of chromaffin cells have been extensively studied.

The synaptic bouton acts like a salt shaker.

The physiological quantal responses at the neuromuscular junction and the bouton-neuron show two classes based on amplitude such that the larger class is about 10 times that of the smaller class; and, the larger class is composed of the smaller class. The ratio of the two classes changes with synaptogenesis, degeneration, nerve stimulation, and is readily altered with various challenges (ionic, tonicity, pharmacological agents). Statistical analyses demonstrate that each bouton or release site at the neruomuscular junction (NMJ) secretes a standard amount of transmitter (one quantum) with each action potential.

Porocytosis: secretion from small and medium-diameter vesicles and vesicle arrays without membrane fusion.

We have recently proposed a mechanism to describe secretion, a fundament process in all cells. That hypothesis, called porocytosis, embodies all available data, and encompasses both forms of secretion, i.e.

Immunocytochemical localization of reelin in the olfactory bulb of the heterozygous reeler mouse: an animal model for schizophrenia.

Because heterozygous reeler (HR) mice share some abnormal traits with schizophrenic patients, and schizophrenia is often accompanied by impairment of olfactory function, this study examines reelin in the olfactory bulb of the HR mouse. In the WT mouse, reelin immunoreactivity is found in the extracellular matrix, and in the cytoplasm of olfactory nerve fibers, GABAergic interneurons, and glutamatergic mitral cells. Western blot analysis reveals that reelin immunoreactivity in the HR mouse is reduced by 45% compared to WT mouse.

Functional and morphological characteristics of bovine adrenal chromaffin cells on macroporous poly(D,L-lactide-co-glycolide) scaffolds.

Adrenal chromaffin cells (ACCs) secrete several neuroactive substances that are effective in influencing pain sensitivity in the central nervous system as well as enhancing the recovery of the intrinsic nigrostriatal dopaminergic system in patients with Parkinson's disease. ACC transplantation may be upregulated by the use of three-dimensional (3-D) scaffolds. In this study, we determined whether biodegradable poly(D,L-lactic-coglycolic acid) (PLGA) (85:15) sponges could be used as support for chromaffin cells.

Proliferation of a subpopulation of reactive astrocytes following needle-insertion lesion in rat.

It is well known that traumatic injuries of the CNS induce a gliotic reaction, characterized by the presence of reactive astrocytes. Reactive astrocytes exhibit enhanced expression of the astrocyte-specific intermediate filament, glial fibrillary acidic protein (GFAP), hypertrophy, and thickened processes. Recently, we have demonstrated that injuries of the CNS induce a re-expression of an embryonic intermediate filament-associated protein, IFAP-70/280 kDa.

ALLEVIATION OF PAIN IN CANCER PATIENTS BY ADRENAL MEDULLARY TRANSPLANTS IN THE SPINAL SUBARACHNOID SPACE.

The treatment of intractable pain with currently available therapeutic regimens is often unsatisfactory due to tolerance and untoward complications. Studies in our laboratory have suggested that the transplantation of adrenal medullary tissue into the spinal subarachnoid space can significantly reduce pain in animal models, most likely via release of opioid peptides and catecholamines. The current study was an initial attempt to assess the potential for adrenal medullary transplants in the spinal subarachnoid space to alleviate pain in humans.

Adrenal medullary implants in the rat spinal cord reduce nociception in a chronic pain model.

Previous work in this laboratory has indicated that the transplantation of adrenal medullary tissue into the subarachnoid space of the rat spinal cord can reduce pain sensitivity to acute noxious stimuli, particularly following stimulation by nicotine. This most likely results from the stimulated release of opioid peptides and catecholamines from the transplanted chromaffin cells. However, chronic pain models may more closely resemble human clinical pain, and the arthritic rat model has been used for screening potential therapeutic strategies.