Aims: At present, clinical success of hepatocyte transplantation as an alternative to whole liver transplantation is hampered by the limited availability of suitable donor organs for the isolation of transplantable hepatocytes. Hence, novel cell sources are required to deliver hepatocytes of adequate quality for clinical use. Mesenchymal stem cells (MSCs) from human bone marrow may have the potential to differentiate into hepatocytes in vitro and in vivo. Methods: Isolated MSCs were selected by density gradient centrifugation and plastic adherence, differentiated in the presence of human hepatocyte growth medium and transplanted in immunodeficient Pfp/Rag2 mice. Results: Here, we demonstrate that human MSCs gain in vitro the characteristic morphology and function of hepatocytes in response to specified growth factors. Specifically, preconditioned MSCs store glycogen, synthesise urea and feature the active hepatocyte-specific gene promoter of phosphoenolpyruvate carboxykinase (PCK1). After transplantation into livers of immunodeficient mice, preconditioned MSCs engraft predominantly in the periportal portion of the liver lobule. In situ, the cells continue to store glycogen and express PCK1, connexin32, albumin and the human hepatocyte-specific antigen HepPar1, indicating that the transplanted cells retain prominent qualities of hepatocytes after their regional integration. Conclusion: MSCs derived from human bone marrow may serve as a novel source for the propagation of hepatocyte-like cells suitable for cell therapy in liver diseases.
Neurologic complications are reported frequently and with high occurrence rate, especially with venoarterial extracorporeal membrane oxygenation, and associated with high mortality calling for daily weaning from sedation and neuromuscular blockers for neurologic assessment and coagulation monitoring. The low quality of evidence indicates the need for higher quality studies in this context.
Objectives: To present a patient with acute hemorrhagic leukoencephalitis (AHLE) and a systematic review of the literature analyzing diagnostic procedures, treatment, and outcomes of AHLE. Methods: PubMed and Cochrane databases were screened. Papers published since 01/01/2000 describing adult patients are reported according to the PRISMA-guidelines. Results: A 59-year old male with rapidly developing coma and cerebral biopsy changes compatible with AHLE is presented followed by 43 case reports from the literature including males in 67% and a mean age of 38 years. Mortality was 47%. Infectious pathogens were reported in 35%, preexisting autoimmune diseases were identified in 12%. Neuroimaging revealed uni-or bihemispheric lesions in 65% and isolated lesions of the cerebellum, pons, medulla oblongata or the spinal cord without concomitant hemispheric involvement in 16%. Analysis of the cerebrospinal fluid showed an increased protein level in 87%, elevated white blood cells in 65%, and erythrocytes in 39%. Histology (reported in 58%) supported the diagnosis of AHLE in all cases. Glucocorticoids were used most commonly (97%), followed by plasmapheresis (26%), and intravenous immunoglobulins (12%), without a clear temporal relationship between treatment and the patients' clinical course. Conclusions: Although mortality was lower than previously reported, AHLE remains a life-threatening neurologic emergency with high mortality. Diagnosis is challenging as the level of evidence regarding the diagnostic yield of clinical, neuroimaging and laboratory characteristics remains low. Hence, clinicians are urged to heighten their awareness and to prompt cerebral biopsies in the context of rapidly progressive neurologic decline of unknown origin with the concurrence of the compiled characteristics. Future studies need to focus on treatment characteristics and their effects on course and outcome.
We examined the presence of WT1-specific mRNA in bone marmyeloid leukemia (AML) has been demonstrated. Several row samples of 125 patients with de novo acute myeloid leukeauthors [10][11][12][13][14][15][16][17] have shown that in the majority of AML cases mia at diagnosis by two-step RT-PCR. The sensitivity of the WT1 is expressed. In view of these findings it was of interest assay was 1:100 (first step) and 1:10 000 (second step), to see whether WT1 positivity or negativity is associated with respectively. WT1-specific mRNA was detected in 73% of specific known features of AML or might be useful as a prog- to the French-American-British (FAB) Acute Leukemia Coop-
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.