ABSTRACT
In previous studies, we have demonstrated that spinal grafting of human or rat fetal spinal neural precursors leads to amelioration of spasticity and improvement in ambulatory function in rats with spinal ischemic injury. In the current study, we characterize the survival and maturation of three different human embryonic stem (ES) cell line-derived neural precursors (hNPCs) once grafted into ischemia-injured lumbar spinal cord in rats or in naive immunosuppressed minipigs. Proliferating HUES-2, HUES-7, or HUES-9 colonies were induced to form embryoid bodies. During the nestin-positive stage, the rosettes were removed and CD184(+)/CD271(-)/CD44(-)/CD24(+) population of ES-hNPCs FAC-sorted and expanded. Male Sprague-Dawley rats with spinal ischemic injury or naive immunosuppressed Gottingen-Minnesota minipigs received 10 bilateral injections of ES-NPCs into the L2-L5 gray matter. After cell grafting, animals survived for 2 weeks to 4.5 months, and the presence of grafted cells was confirmed after staining spinal cord sections with a combination of human-specific (hNUMA, HO14, hNSE, hSYN) or nonspecific (DCX, MAP2, CHAT, GFAP, APC) antibodies. In the majority of grafted animals, hNUMA-positive grafted cells were identified. At 2-4 weeks after grafting, double-labeled hNUMA/DCX-immunoreactive neurons were seen with extensive DCX(+) processes. At survival intervals of 4-8 weeks, hNSE(+) neurons and expression of hSYN was identified. Some hSYN-positive terminals formed putative synapses with the host neurons. Quantitative analysis of hNUMA(+) cells at 2 months after grafting showed comparable cell survival for all three cell lines. In the presence of low-level immunosuppression, no grafted cell survival was seen at 4.5 months after grafting. Spinal grafting of proliferating pluripotent HUES-7 cells led to consistent teratoma formation at 2-6 weeks after cell transplantation. These data show that ES-derived, FAC-sorted NPCs can represent an effective source of human NPCs to be used in CNS cell replacement therapies.
Subject(s)
Embryonic Stem Cells/cytology , Neural Stem Cells/transplantation , Spinal Cord Ischemia/therapy , Animals , Antigens, Nuclear/metabolism , Cell Cycle Proteins , Cell Differentiation , Cell Line , Cell Survival , Doublecortin Protein , Embryoid Bodies/physiology , Embryonic Stem Cells/metabolism , Humans , Immunocompromised Host , Ki-67 Antigen/metabolism , Male , Mice , Neural Stem Cells/cytology , Neural Stem Cells/metabolism , Neurons/metabolism , Nuclear Matrix-Associated Proteins/metabolism , Rats , Rats, Sprague-Dawley , Spinal Cord Ischemia/metabolism , Spinal Cord Ischemia/pathology , Swine , Swine, Miniature , Transcription Factors/metabolismABSTRACT
Central nervous system (CNS) lymphoma is a common complication of patients with HIV infection occurring in as many as 20% of patients with AIDS. This article reviews current observations on primary CNS lymphoma and systemic AIDS-related lymphoma with CNS involvement. Clinical features, diagnosis, differential diagnosis, clinical course, and therapeutic options are herein reviewed.
Subject(s)
Central Nervous System Neoplasms , Lymphoma, AIDS-Related , HumansABSTRACT
Treatment of the Dandy-Walker syndrome has included placement of a ventriculoperitoneal shunt alone or in combination with a posterior fossa cystoperitoneal shunt. Complications in shunting are common and are usually related to malfunction or infection. The authors present a case in which the patient developed headaches and focal cranial nerve deficits following infection caused by a cystoperitoneal shunt. Magnetic resonance imaging showed tethering of the brainstem. A posterior fossa craniotomy with microsurgical untethering and cyst fenestration achieved two goals: improvement of the focal cranial nerve deficits and elimination of the cystoperitoneal shunt.
Subject(s)
Brain Stem/physiopathology , Cerebrospinal Fluid Shunts , Dandy-Walker Syndrome/surgery , Postoperative Complications , Brain Stem/surgery , Child, Preschool , Cranial Fossa, Posterior , Cranial Nerves/physiopathology , Follow-Up Studies , Headache/etiology , Humans , Magnetic Resonance Imaging , Male , Ventriculoperitoneal ShuntABSTRACT
PURPOSE: A clinical trial was undertaken to determine the safety and efficacy of combining a biologic response modifier derived from the bacterium Serratia marcescens (ImuVert) and radiation therapy (RT) in patients with newly diagnosed anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM). PATIENTS AND METHODS: Fifteen patients who had undergone either a gross total resection, a partial resection, or a biopsy were treated concurrently with ImuVert and RT. Safety and tolerance were examined by assessment of symptomatic reactions recorded at each ImuVert treatment. Efficacy of treatment was examined in terms of time to progression of tumor and survival. RESULTS: All patients experienced local reactions at the injection sites that consisted of erythema and induration. The majority of patients experienced flu-like symptoms. Hypotension was responsible for the most significant morbidity (which required fluid resuscitation and extended observation) and dose deescalation. No patients were removed from the study because of toxicity. There were no on-study deaths related to ImuVert treatment. Median time to progression was 33.4 weeks, and median survival was 78 weeks. CONCLUSION: These results compare favorably with those of recent studies in patients with malignant astrocytomas who received multimodality therapy.
