Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Survival and differentiation of human embryonic stem cell-derived neural precursors grafted spinally in spinal ischemia-injured rats or in naive immunosuppressed minipigs: a qualitative and quantitative study. 2288 56

Patients with chronic stroke have currently little hope for motor improvement towards regaining independent activities of daily living; stem cell treatments offer a new treatment option and needs to be developed. Patients with chronic stroke (more than 3 months prior to stem cell treatment, mean 21.2 months post-stroke) were treated with CD271+ stem cells, 7 patients received autologous and 1 allogeneic cells from first degree relative; administration was intravenous in 1 and intrathecal in 7 patients. Each patient received a single treatment consisting of 2-5x106 cells/kg and they were followed up for up to 12 months. There were significant improvements in expressive aphasia (2/3 patients) spasticity (5/5, of which 2 were transient), and small improvements in motor function (2/8 patients). Although motor improvements were minor in our chronic stroke patients, improvements in aphasia and spasticity were significant and in the context of good safety we are advocating further administration and clinical studies of CD271+ stem cells not only in chronic stroke patients, but also for spastic paresis/plegia; a different, yet unexplored application is pulmonary emphysema.
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PMID:CD271+ stem cell treatment of patients with chronic stroke. 3278 17