Histology and histopathology Vol.26, nº7 (2011)

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http://hdl.handle.net/10201/177377

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Open Access
Immunosuppressive cells and tumour microenvironment: Focus on mesenchymal stem cells and myeloid derived suppressor cells
(F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Bianchi, Giovanna; Borgonovo, Giacomo; Pistoia, Vito; Raffaghello, Lizzia
Tumours have been compared to unhealed wounds that produce large amounts of inflammatory mediators, including cytokines, chemokines, and growth factors. These molecules participate in the formation of a rich and heterogeneous microenvironment by attracting non malignant cells that promote tumour progression and dissemination. Tumour infiltrating cells include macrophages, myeloid-derived suppressor cells (MDSCs), mesenchymal stromal cells (MSCs) and TIE2-expressing monocytes. Most of them are bone marrow-derived, although MSC are present in virtually every tissue. This review focuses on MDSCs and MSCs, both of which can exert pro-tumorigenic effects through negative regulation of immune responses. MDSCs represent a heterogeneous population of cells of myeloid origin that are expanded and activated in response to growth factors and cytokines released by tumours. Once MDSCs are activated, they accumulate in lymphoid organs and tumours where they exert T cell immunosuppression. Like MDSCs, MSCs can be mobilized from the bone marrow into the bloodstream and home in the tumour stroma, where they either help or hinder tumour growth. Here, we will discuss the origin, the functions and the mechanisms of action of MSCs and MDSCs, as well as the strategies to target these cells for the therapeutic benefit of cancer patients.
Open Access
The function of TRPS1 in the development and differentiation of bone, kidney, and hair follicles
(F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Gai, Zhibo; Gui, Ting; Muragaki, Yasuteru
TRPS1 is a gene involved in Tricho-rhino-phalangeal syndrome (TRPS), an autosomal dominant skeletal disorder. TRPS1 encodes a GATA-type transcription factor that has nine zinc-finger motifs. A variety of mutations in TRPS1 including deletions and insertions, have been found in patients with TRPS type I and III. The functions of each domain of TRPS1 have been clarified from study of these mutations. Further studies on the localization and the function of TRPS1 have been performed using TRPS1Δgt and Trps1-deficient mice, which allow examination of the development and differentiation of all tissues with Trps1 expression. These studies suggest that TRPS1 exhibits a variety of functions in cartilage, kidneys, and hair follicles. In the growth plate cartilage, TRPS1 regulates the differentiation, proliferation, and apoptosis of chondrocytes through interaction of several signaling molecules. In addition, TRPS1 has a function downstream of BMP7, which regulates the mesenchymal-epithelial transition when nephrons are formed in renal development. Furthermore, TRPS1 suppresses the epithelial-mesenchymal transition and renal fibrosis induced by unilateral ureteral obstruction by decreasing Arkadia expression. Finally, TRPS1 is expressed in the dermal papillae and the mesenchymal cells surrounding the hair pegs, and the loss of TRPS1 largely influences the development of hair follicles. The molecular mechanisms of the function of TRPS1 in cartilage, kidneys, and hair follicles are discussed in this review.
Open Access
Cell- and gene-therapy approaches to inner ear repair
(F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Conde de Felipe, M.M.; Feijoo Redondo, A.; García-Sancho, J.; Schimmang, T.; Durán Alonso, M.B.
Sensorineural hearing loss is the most common sensory disorder in humans. It is primarily due to the degeneration of highly specialised mechanosensory cells in the cochlea, the so-called hair cells. Hearing problems can also be caused or further aggravated by the death of auditory sensory neurons that convey the information from the hair cells to the brain stem. Despite the discovery of stem/progenitor cells in the mammalian cochlea, no regeneration of either damaged hair cells or auditory neurons has been observed in mammals, in contrast to what is seen in avians and non-mammalian vertebrates. The reasons for this divergence have not yet been elucidated, although loss of stem cells and/or loss of their phenotypic plasticity in adult mammals have been put forward as possible explanations. Given the high incidence of this disorder and its economic and social implications, a considerable number of research lines have been set up aimed towards the regeneration of cochlear sensory cell types. This review summarizes the various routes that have been explored, ranging from the genetic modification of endogenous cells remaining in the inner ear in order to promote their transdifferentiation, to the implantation of exogenous stem or progenitor cells and their subsequent differentiation within the host tissue. Prophylactic treatments to fight against progressive sensory cell degeneration in the inner ear are also discussed.
Open Access
Prospective evaluation of the learning curve of confocal laser endomicroscopy in patients with IBD
(F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Neumann, Helmut; Vieth, Michael; Atreya, Raja; Neurath, Markus F.; Mudter, Jonas
Background and aims: Confocal laser endomicroscopy (CLE) represents a novel endoscopic imaging technique which enables the in vivo microscopic imaging within the mucosal layer of the gut at subcellular resolution. Currently, there are no data available on the learning curve of CLE, which was therefore the aim of our study. Methods: Twenty-six consecutive patients with inflammatory bowel disease (IBD) underwent total colonoscopy and were examined by fluorescein-aided CLE. Image data were collected and reviewed by two endoscopists in a blinded fashion. CLE images were compared to endoscopical and histological findings. Prospectively, the following performance parameters were documented: total duration of the procedure, confocal imaging time, time to receive a confocal image in focus, number of confocal images, number of confocal images in focus, CLE diagnosis and final histopathological diagnosis. Results: A significance decrease of CLE duration was detected between the first 8 and the subsequent cases (p=0.002). Confocal imaging time and the time to receive an image in focus declined significantly over time (p=0.0001), while number of images in focus significantly increased (p=0.0007). Agreement between CLE and histopathology improved over time with kappa values of 0.81 after twenty-six cases. Conclusions: There was a significant improvement in CLE performance over time, including decreased confocal imaging time, successful CLE diagnosis and decline in procedural time. These parameters improved significantly after the initial three cases. Therefore, CLE represents an easy to learn and apply novel diagnostic method for in vivo analysis and diagnosis in IBD.
Open Access
Biological effects of low-frequency pulsed magnetic fields on the embryonic central nervous system development. A histological and histochemical study
(F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Roda, Olga; Garzón, Ingrid; Carriel, Víctor; Alaminos, Miguel; Sánchez-Montesinos, Indalecio
Numerous experiments have yielded contradictory results on the harmful action of magnetic fields on embryonic development. Pulsed magnetic fields appear to be able to delay normal development of embryos. In the present study, fertilized Gallus domesticus eggs were exposed during incubation to pulsed magnetic fields (harmonic signals of 10 µT for 1 second with silences of 0.5 seconds) of 50 or 100 Hz frequency. Embryos extracted at 45 h of exposure to fields of 50 Hz or 100 Hz frequency had significantly (p<0.05) fewer somite pairs compared with controls of the same age. At 15 days of incubation, only embryos exposed to a 10 µT- 50 Hz field had a significantly (p<0.05) higher somatic weight. At 21 days of incubation, a significantly lower somatic weight (p<0.01) and development stage (p<0.05) was found in embryos exposed to a 10 µT-100 Hz field than in controls, while a lower development stage (p<0.05) alone was observed in those exposed to a 10 µT-50 Hz field. In addition, animals showed higher expression of the neural marker NSE (neural specific enolase) after 21 days of development as determined by immunohistochemistry, with very low expression of glycosaminoglycans identified by alcyan blue staining. These results suggest that pulsed magnetic fields may be able to hinder normal embryonic development in vivo and to alter normal neural function, at least at the intensities and frequencies analyzed in the present study

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