Interpeduncular cistern intrathecal targeted drug delivery for intractable postherpetic neuralgia: A case report.

BACKGROUND: Intractable postherpetic neuralgia (PHN) can be difficult to manage even with aggressive multimodal therapies. Patients who experience uncontrolled refractory cranial PHN despite conservative treatment may benefit from an intrathecal drug delivery system (IDDS). For craniofacial neuropathic pain, the traditional approach has been to place the intrathecal catheter tip below the level of the cranial nerve root entry zones, which may lead to insufficient analgesia. CASE SUMMARY: We describe a 69-year-old man with a 1-year history of PHN after developing a vesicular rash in the ophthalmic division of cranial nerve V (trigeminal nerve) distribution. The pain was rated 7-8 at rest and 9-10 at breakthrough pain (BTP) on a numeric rating scale. Despite receiving aggressive multimodal therapies including large doses of oral analgesics (gabapentin 150 mg q12 h, oxycodone 5 mg/acetaminophen 325 mg q6 h, and lidocaine 5% patch 700 mg q12 h) and sphenopalatine ganglion block, there was no relief of pain. Subsequently, the patient elected to have an implantable IDDS with the catheter tip placed at the interpeduncular cistern. The frequency of BTP episodes decreased. The patient's continuous daily dose was adjusted to 0.032 mg/d after 3 mo of follow-up and stopped 5 mo later. He did not report pain or other discomfort at outpatient follow-up 6 mo and 1 year after stopping intracisternal hydromorphone. CONCLUSION: The use of interpeduncular cistern intrathecal infusion with low-dose hydromorphone by IDDS may be effective for severe craniofacial PHN.

Characterization and neural differentiation of fetal lung mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have been successfully isolated from a broad range of adult, fetal, and other nonembryonic tissues. Fetal lung has been identified as a rich source of MSCs. However, the biological characteristics and differentiation potential of fetal lung MSCs remain to be explored. In this study, we established a series of methods for isolation and expansion of fetal lung MSCs. These MSCs could withstand more than 40 passages without obvious decline in proliferation ability, significant changes in morphology, and expression of cell markers. Flow cytometric analysis showed that fetal lung MSCs expressed CD13, CD29, CD44, CD90, CD105, CD166, and HLA-ABC, but not CD14, CD31, CD34, CD38, CD41a, CD42b, CD45, CD49d, CD61, CD106, CD133, and HLA-DR. Cell cycle analysis revealed that when the MSCs reached their log phase of growth, more than 90% of the cells were in G0/G1 phase while the proportion of cells in S phase and G2/M phase were about 5.56% and 2.08% cells, respectively. These MSCs could differentiate into neural cells in addition to their mesenchymal differentiation potential. Our data suggest that the fetal lung MSC population is an alternative source of stem cells for cell-based therapy of neurological defects or mesenchymal-originating diseases.

[Intra-bone marrow cavity transplantation of human umbilical cord blood mononuclear cells into NOD/SCID mice].

OBJECTIVE: To evaluate the hematopoietic reconstitution of implanted NOD/SCID mice, after intra-bone marrow cavity injection (iBM) of human umbilical cord blood (CB) mononuclear cells (MNCs). METHODS: 24 female NOD/SCID mice were divided into different MNCs dosage iBM groups (3 x 10(6), 1 x 10(7), 3 x 10(7) cells), tail vein intravenous injection (iTV) group (3 x 10(7) cells) and control group (iBM of medium only). CB MNCs sorted by Ficoll-Hypaque were transplanted into left tibia bone marrow cavity of 6- to 8-week-old NOD/SCID mice, which were anesthetized and sublethally irradiated (270 cGy (137)Cs-gamma irradiation). The distribution of injected CB MNCs in noninjected right tibia of the same implanted mice was observed 24 hours after iBM. The establishment of hematopoiesis and the survival of mice were observed. BM cell surface CD marker expressions, dye Dil-CM tracing and human beta-actin from implanted mice were assessed 8 weeks after iBM or iTV. RESULTS: Dil-CM marker could be detected on BM cells from noninjected right tibia 24 hours after iBM. Fourteen engrafted mice survived at the end of our study. Among them two, four and five were of iBM-1, iBM-2 and iBM-3 groups respectively, and one of control group and two of iTV group. White blood cell reconstitution was better in iBM mice than in iTV and control mice. There were human markers including CD45, Dil-CM and beta-actin DNA in the marrow cells from the human CB MNC engrafted mice. CONCLUSION: The preliminary results showed that hematopoiesis reconstitution by iBM was significantly better than iTV.

Human umbilical cord blood cells express neurotrophic factors.

Freshly isolated or culture-expanded human umbilical cord blood mononuclear cells (CBMNCs) have been known to express neural phenotypes in vitro and to differentiate into neural cells and improve neurological function recovery after being administrated into rodent models of neurological diseases. However, the mechanism of action remains unclear. The present study observed that CBMNCs expressed higher level mRNAs of several neurotrophic factors than adult peripheral blood mononuclear cells (PBMCs). In addition, a significantly increase in the levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT4/5) was found in culture supernatants of CBMNCs compared to that of PBMNCs. These findings indicate that CBMNCs express several neurotrophic factors and suggest that the neurotrophic factors secreted by CBMNCs may be responsible for amelioration of central nervous system deficits in animal models after CBMNC administration.

[In vitro vasculogenesis and angiogenesis of mouse embryonic stem cells].

OBJECTIVE: To explore an optional condition to induce mouse embryonic stem (ES) cells to differentiate into endothelial cells and to establish in vitro models of vasculogenesis and angiogenesis. METHODS: Mouse ES cells were cultured in differentiation medium containing a cocktail of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-6 (IL-6) and erythropoietin (EPO) in 1% methylcellulose to induce formation of embryoid bodies (EBs). At day 11, EBs were harvested and suspended in rat-tail collagen type I with the same cocktail of cytokines cultured for three additional days. The differentiation of ES cells into endothelial cells, processes of vasculogenesis and angiogenesis were examined using immunostaining of EBs slices and whole-mount immunocytochemistry of EBs with monoclonal antibodies (mAbs) against platelet endothelial cell adhesion molecule-1 (PECAM-1) and alpha-smooth muscle actin (SMA). RESULTS: Under appropriate culture conditions; ES cells spontaneously differentiated and formed EBs containing vascular structures and tubular channels, which were positive for PECAM-1 co-differentiated with smooth muscle. When not treated with angiogenic growth factors, PECAM-1-positive cells could not organize into vascular structures of 11-day-old EBs. In the presence of angiogenic factors 11-day old EBs embedded into type I collagen, and rapidly developed an endothelial networks. Whole-mount immunocytochemistry of collagen gel with anti-PECAM-1 antibody showed the formation of primary vascular structures sprouting from EBs. Quantitative analysis revealed that 100 microg/ml thalidomide significantly reduced the number and length of EBs endothelial sprouting. CONCLUSIONS: Mouse ES cells can differentiate into endothelial cells combined with smooth muscle differentiation during EBs formation and further develop endothelial outgrowths after EBs embedded into collagen, which respectively recapitulate vasculogenesis, angiogenesis, and arteriogenesis processes in vivo. The models provide a useful tool to investigate vasculogenesis, angiogenesis, and arteriogenesis mechanisms and evaluate the effects of angiogenic and angiostatic agents.