ABSTRACT
Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra leading to disabling deficits. Dopamine neuron grafts may provide a significant therapeutic advance over current therapies. We have generated midbrain dopamine neurons from human embryonic stem cells and manufactured large-scale cryopreserved dopamine progenitors for clinical use. After optimizing cell survival and phenotypes in short-term studies, the cell product, MSK-DA01, was subjected to an extensive set of biodistribution, toxicity, and tumorigenicity assessments in mice under GLP conditions. A large-scale efficacy study was also performed in rats with the same lot of cells intended for potential human use and demonstrated survival of the grafted cells and behavioral amelioration in 6-hydroxydopamine lesioned rats. There were no adverse effects attributable to the grafted cells, no obvious distribution outside the brain, and no cell overgrowth or tumor formation, thus paving the way for a future clinical trial.
Subject(s)
Dopamine , Human Embryonic Stem Cells , Animals , Cell Differentiation , Dopaminergic Neurons , Mesencephalon , Mice , Rats , Tissue DistributionABSTRACT
Malignant Mesothelioma is an uncommon tumor that usually presents with diffuse pleural involvement and carries a dismal prognosis. Rarely, however, it can present as a localized, circumscribed mass or focal pleural lesion without evidence of diffuse spread. We found four such cases in our database. Three patients had localized epithelioid malignant mesothelioma and one had localized sarcomatoid mesothelioma. These localized tumors are a potential diagnostic pitfall for the pathologists as well as radiologists, especially those practicing in a community setting. Herein we discuss the clinicopathologic features of our cases along with a review of literature.
Subject(s)
Combined Modality Therapy/methods , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Mesothelioma/pathology , Mesothelioma/therapy , Adult , Aged , Carboplatin/therapeutic use , Cisplatin/therapeutic use , Fatal Outcome , Female , Humans , Male , Mesothelioma, Malignant , Pemetrexed/therapeutic use , Radiotherapy , Thoracic Surgical ProceduresABSTRACT
Human pluripotent stem cells (PSCs) provide an unlimited cell source for cell therapies and disease modeling. Despite their enormous power, technical aspects have hampered reproducibility. Here, we describe a modification of PSC workflows that eliminates a major variable for nearly all PSC experiments: the quality and quantity of the PSC starting material. Most labs continually passage PSCs and use small quantities after expansion, but the "just-in-time" nature of these experiments means that quality control rarely happens before use. Lack of quality control could compromise PSC quality, sterility, and genetic integrity, which creates a variable that might affect results. This method, called CryoPause, banks PSCs as single-use, cryopreserved vials that can be thawed and immediately used in experiments. Each CryoPause bank provides a consistent source of PSCs that can be pre-validated before use to reduce the possibility that high levels of spontaneous differentiation, contamination, or genetic integrity will compromise an experiment.
Subject(s)
Cryopreservation/methods , Pluripotent Stem Cells/cytology , Animals , Biological Specimen Banks , Cell Differentiation , Cell Line , Cell- and Tissue-Based Therapy , Gene Editing , Humans , Mice , Pluripotent Stem Cells/metabolism , Pluripotent Stem Cells/transplantationABSTRACT
Although endometriosis of the pelvic organs is common, endometriosis of the urinary bladder is extremely rare. Malignant transformation of atypical endometriotic foci is an uncommon but well-documented sequela, occurring in approximately 1% of cases. This article reports the fourth case in the English literature of clear cell carcinoma arising from foci of endometriosis within the posterior bladder wall.
