ABSTRACT
Mesenchymal stem cells (MSCs) of placental origin hold great promise in tissue engineering and regenerative medicine for diseases affecting cartilage and bone. However, their utility has been limited by their tendency to undergo premature senescence and phenotypic drift into adipocytes. This study aimed to explore the potential involvement of a specific subset of aging and antiaging genes by measuring their expression prior to and following in vitro-induced differentiation of placental MSCs into chondrocytes and osteoblasts as opposed to adipocytes. The targeted genes of interest included the various LMNA/C transcript variants (lamin A, lamin C, and lamin A∆10), sirtuin 7 (SIRT7), and SM22α, along with the classic aging markers plasminogen activator inhibitor 1 (PAI-1), p53, and p16INK4a. MSCs were isolated from the decidua basalis of human term placentas, expanded, and then analyzed for phenotypic properties by flow cytometry and evaluated for colony-forming efficiency. The cells were then induced to differentiate in vitro into chondrocytes, osteocytes, and adipocytes following established protocols. The mRNA expression of the targeted genes was measured by RT-qPCR in the undifferentiated cells and those fully differentiated into the three cellular lineages. Compared to undifferentiated cells, the differentiated chondrocytes demonstrated decreased expression of SIRT7, along with decreased PAI-1, lamin A, and SM22α expression, but the expression of p16INK4a and p53 increased, suggesting their tendency to undergo premature senescence. Interestingly, the cells maintained the expression of lamin C, which indicates that it is the primary lamin variant influencing the mechanoelastic properties of the differentiated cells. Notably, the expression of all targeted genes did not differ from the undifferentiated cells following osteogenic differentiation. On the other hand, the differentiation of the cells into adipocytes was associated with decreased expression of lamin A and PAI-1. The distinct patterns of expression of aging and antiaging genes following in vitro-induced differentiation of MSCs into chondrocytes, osteocytes, and adipocytes potentially reflect specific roles for these genes during and following differentiation in the fully functional cells. Understanding these roles and the network of signaling molecules involved can open opportunities to improve the handling and utility of MSCs as cellular precursors for the treatment of cartilage and bone diseases.
Subject(s)
Cell Differentiation , Chondrogenesis , Mesenchymal Stem Cells , Osteogenesis , Placenta , Humans , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Female , Placenta/metabolism , Placenta/cytology , Cell Differentiation/genetics , Chondrogenesis/genetics , Pregnancy , Osteogenesis/genetics , Biomarkers/metabolism , Cellular Senescence/genetics , Chondrocytes/metabolism , Chondrocytes/cytology , Aging , Lamin Type A/metabolism , Lamin Type A/geneticsABSTRACT
Guillain-Barré syndrome (GBS) is a rare immune-mediated neuropathy causing destruction of the peripheral nervous system, with molecular mimicry playing a major role in its pathophysiology. Despite its rarity, it is considered the most common cause of acute flaccid neuromuscular paralysis in the United States. Although diagnosing GBS depends on the clinical presentation of the patient, cerebrospinal fluid sampling, nerve conduction studies, electromyography, magnetic resonance imaging, and ganglioside antibody screening can be used to confirm the diagnosis and rule out other differentials. Here, we report a rare case of GBS as a postoperative complication after a successful gastrojejunostomy to excise an adenocarcinoma in the second part of the duodenum. Such a complication is rare and not fully understood yet.
ABSTRACT
Rosai-Dorfman Disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is an uncommon histiocytic condition characterized by massive histopathological aggregation of CD1-a negative, CD68-positive, and S100-positive histiocytes. It was initially described by Destombes in 1965 under the term "adenitis with lipid excess." However, it is named after Rosai and Dorfman who reported further histopathological features of the disease in 1969. The diagnosis of this non-Langerhans cell histiocytosis can be challenging and requires high clinical suspicion. The diagnostic process usually involves imaging, tissue biopsies, and genetic testing as needed. In this case series, we are presenting three cases of rare disease. Case 2 had both nodal and extranodal forms, which makes this case rarer than cases 1 and 3, which present with extranodal lesions.