ABSTRACT: Bone marrow-derived mesenchymal stem cells are pluripotent cells that are capable of differentiating into a variety of cell types including neuronal cells, osteoblasts, chondrocytes, myocytes, and adipocytes. Despite recent advances in stem cell biology, neuroendocrine relations, particularly TSH interactions remain elusive. In this study, we investigated expression and biological consequence of TSH receptor (TSHR) interactions in mesenchymal stem cells of cultured human bone marrow. To the best of our knowledge, we demonstrated for the first time that human bone marrow-derived mesenchymal stem cells expressed a functional thyrotropin receptor that was capable of transducing signals through cAMP. We extended this study to explore possible pathways that could be associated directly or indirectly with the TSHR function in mesenchymal stem cells. Expression of 80 genes was studied by real-time PCR array profiles. Our investigation indicated involvements of interactions between TSH and its receptor in novel regulatory pathways, which could be the important mediators of self-renewal, maintenance, development, and differentiation in bone marrow-derived mesenchymal stem cells. TSH enhanced differentiation to the chondrogenic cell lineage; however, further work is required to determine whether osteoblastic differentiation is also promoted. Our results presented in this study have opened an era of regulatory events associated with novel neuroendocrine interactions of hypothalamic-pituitary axis in mesenchymal stem cell biology and differentiation.
Journal of Endocrinology 11/2011; 212(2):169-78. · 3.55 Impact Factor
ABSTRACT: This study aimed to investigate the effects of anandamide or arachidonylethanolamide (AEA), an endogenous cannabinoid receptor agonist, on intraocular inflammation in an endotoxin-induced uveitis (EIU) model in rabbits.
Forty New Zealand albino male rabbits were used (5 groups, 8 animals in each). After establishment of sufficient anesthesia, animals were taken under surgery for intravitreal injections. A maximum amount of 50 μL of solution was injected into the central vitreous with a 30-gauge needle. In the control group, sterile saline was injected into the right eyes of the animals. Likewise, AEA (10(-5) M) in the second group, lipopolysaccharide (LPS; 100 ng) in the third group, and AEA (10(-5) M) and LPS (100 ng) in the fourth group were administered. Fifth group received 0.1 mL subtenon injection of AM251 (10(-5) M), a CB(1)-receptor antagonist, 30 min prior to intravitreal LPS (100 ng) and AEA (10(-5) M) injection. At 24 h after the surgical intervention, clinical evaluation was performed and animals were then euthanized with 100 mg/kg intravenous pentobarbital injections. Immediately after the induction of pentobarbital anesthesia, the anterior chamber of the eyes was quickly punctured using a 30-gauge needle to drain aqueous humor (AH) and obtained specimens were used for cell count, protein measurement, and microbiological contamination tests. After AH collection, enucleation was performed and enucleated material was kept for the pathological evaluation.
AEA caused an overall worsening of EIU in studied eyes. It significantly increased the detrimental effects of endotoxin, as assessed by clinical investigation of ocular inflammation, AH leukocyte content, and AH protein concentrations. CB(1)-receptor antagonist AM251 administration reversed some components of this AEA-induced exacerbation to significant extents.
AEA exacerbated EIU in rabbit eyes. AM251 has been found beneficial to prevent AEA's aggravating impact on EIU. As AEA is a treatment choice for lowering intraocular pressure in ophthalmology practice, concurrent use of CB(1)-receptor antagonists may be a questionable strategy in cases of secondary glaucoma, to avoid aggravation of the present inflammation.
Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 08/2011; 27(6):545-52. · 1.46 Impact Factor
ABSTRACT: Anaplastic pleomorphic xanthoastrocytoma is an aggressively growing, malignant, and eventually fatal tumor of the central nervous system. Testing chemotherapeutic drug sensitivity under in vitro conditions would be a useful strategy to determine sensitive or resistant drugs for fatal brain cancers.
To establish primary cell cultures of excised tumor tissue from pleomorphic xanthoastrocytoma-bearing patients and to test their sensitivity against various anticancer chemotherapy drugs.
Prepared suspensions of the excised tumor tissue from a patient who had a recurrent grade 3 pleomorphic xanthoastrocytoma was cultured in culture dishes until cells began to grow. Immunofluorescent and immunohistochemical visualizations were performed using confocal and light microscopy. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in comparison with ³H-thymidine incorporation assay was used to test cellular toxicity of several anticancer drugs.
We established vigorously growing primary cells of the tumor. Drug sensitivity testing was conducted successfully.
Primary cell cultures of surgically removed tumor tissues may be useful in studies of cancer biology and chemotherapeutic drug sensitivity for recurrent malignant brain tumors, particularly for anaplastic pleomorphic xanthoastrocytoma.
Neurosurgery 05/2011; 70(1):188-97. · 2.79 Impact Factor