|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Theta Phase Classification of Interneurons in the Hippocampal Formation of Freely Moving Rats. J Neurosci. 2011 Feb 23;31(8):2938-2947 Authors: Czurkó A, Huxter J, Li Y, Hangya B, Muller RU Earlier work on freely moving rats classified neurons in Ammon's horn as pyramidal cells (including place cells) or interneurons (previously called "theta cells") based on temporal discharge correlates and waveform configurations, but the anatomical and biochemical diversity of interneurons suggests they may have other distinguishing characteristics. To explore this possibility, we made extracellular recordings as rats foraged for food in an open space, used accepted criteria to identify interneurons, and found two additional categorization methods. First, interneurons were separated into theta-modulated and theta-independent groups using spike autocorrelograms. Second, theta-modulated interneurons were further separated into four groups by the phase of the ∼8 Hz theta rhythm at which firing was most rapid. These phase groups resemble the four phase peak groups of five anatomically identified interneuron types (two with the same preferred phase) recorded during the slow (∼4 Hz) theta rhythm in urethane-anesthetized rats. We suggest that the similar number of peak phase groups in walking rats and urethane-anesthetized rats and the partial agreement between peak phase values reflect a similar organization of theta rhythm in both states, so that the discharge properties of anatomically identified interneurons can be described in freely moving rats. Interestingly, the average spatial firing precision of the interneuron classes does not differ significantly, suggesting that the strong location-specific firing of place cells may be due to segregated high- and low-precision interneuron ensembles rather than to one or more dedicated high-precision classes. PMID: 21414915 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates. Eur Heart J. 2011 Mar 17; Authors: Weber B, Scherman J, Emmert MY, Gruenenfelder J, Verbeek R, Bracher M, Black M, Kortsmit J, Franz T, Schoenauer R, Baumgartner L, Brokopp C, Agarkova I, Wolint P, Zund G, Falk V, Zilla P, Hoerstrup SP Aims A living heart valve with regeneration capacity based on autologous cells and minimally invasive implantation technology would represent a substantial improvement upon contemporary heart valve prostheses. This study investigates the feasibility of injectable, marrow stromal cell-based, autologous, living tissue engineered heart valves (TEHV) generated and implanted in a one-step intervention in non-human primates. Methods and results Trileaflet heart valves were fabricated from non-woven biodegradable synthetic composite scaffolds and integrated into self-expanding nitinol stents. During the same intervention autologous bone marrow-derived mononuclear cells were harvested, seeded onto the scaffold matrix, and implanted transapically as pulmonary valve replacements into non-human primates (n = 6). The transapical implantations were successful in all animals and the overall procedure time from cell harvest to TEHV implantation was 118 ± 17 min. In vivo functionality assessed by echocardiography revealed preserved valvular structures and adequate functionality up to 4 weeks post implantation. Substantial cellular remodelling and in-growth into the scaffold materials resulted in layered, endothelialized tissues as visualized by histology and immunohistochemistry. Biomechanical analysis showed non-linear stress-strain curves of the leaflets, indicating replacement of the initial biodegradable matrix by living tissue. Conclusion Here, we provide a novel concept demonstrating that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve delivery as a one-step intervention is feasible in non-human primates. This innovative approach may overcome the limitations of contemporary surgical and interventional bioprosthetic heart valve prostheses. PMID: 21415068 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Intracerebral xenotransplantation: recent findings and perspectives for local immunosuppression. Curr Opin Organ Transplant. 2011 Apr;16(2):190-4 Authors: Lévêque X, Cozzi E, Naveilhan P, Neveu I Cell therapy is a promising strategy for tissue repair in the central nervous system. In this perspective, several cell types are being considered, including allogenic neuroblasts, embryonic stem cells and induced pluripotent stem cells. The use of allogenic neuroblasts as cell source is limited by logistics and ethical problems whereas transplantation of the last two cell types is hampered by their propensity to generate tumour. In this context, transplantation of xenogeneic neural cells appears as an attractive approach for effective neuronal replacement in case of neurodegenerative disorders. PMID: 21415822 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Progress in understanding reprogramming to the induced pluripotent state. Nat Rev Genet. 2011 Apr;12(4):253-65 Authors: Plath K, Lowry WE Induction of pluripotency by transcription factors has become a commonplace method to produce pluripotent stem cells. Great strides have been made in our understanding of the mechanism by which this occurs - particularly in terms of transcriptional and chromatin-based events - yet only a small part of the complete picture has been revealed. Understanding the mechanism of reprogramming to pluripotency will have important implications for improving the efficiency and quality of reprogramming and advancing therapeutic application of induced pluripotent stem cells. It will also help to reveal the machinery that stabilizes cell identity and to instruct the design of directed differentiation or lineage switching strategies. To inform the next phase in understanding reprogramming, we review the latest findings, highlight ongoing debates and outline future challenges. PMID: 21415849 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Cell-laden microengineered pullulan methacrylate hydrogels promote cell proliferation and 3D cluster formation. Soft Matter. 2011 Jan 1;7(5):1903-1911 Authors: Bae H, Ahari AF, Shin H, Nichol JW, Hutson CB, Masaeli M, Kim SH, Aubin H, Yamanlar S, Khademhosseini A The ability to encapsulate cells in three-dimensional (3D) environments is potentially of benefit for tissue engineering and regenerative medicine. In this paper, we introduce pullulan methacrylate (PulMA) as a promising hydrogel platform for creating cell-laden microscale tissues. The hydration and mechanical properties of PulMA were demonstrated to be tunable through modulation of the degree of methacrylation and gel concentration. Cells encapsulated in PulMA exhibited excellent viability. Interestingly, while cells did not elongate in PulMA hydrogels, cells proliferated and organized into clusters, the size of which could be controlled by the hydrogel composition. By mixing with gelatin methacrylate (GelMA), the biological properties of PulMA could be enhanced as demonstrated by cells readily attaching to, proliferating, and elongating within the PulMA/GelMA composite hydrogels. These data suggest that PulMA hydrogels could be useful for creating complex, cell-responsive microtissues, especially for applications that require controlled cell clustering and proliferation. PMID: 21415929 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Control of the embryonic stem cell state. Cell. 2011 Mar 18;144(6):940-54 Authors: Young RA Embryonic stem cells and induced pluripotent stem cells hold great promise for regenerative medicine. These cells can be propagated in culture in an undifferentiated state but can be induced to differentiate into specialized cell types. Moreover, these cells provide a powerful model system for studies of cellular identity and early mammalian development. Recent studies have provided insights into the transcriptional control of embryonic stem cell state, including the regulatory circuitry underlying pluripotency. These studies have, as a consequence, uncovered fundamental mechanisms that control mammalian gene expression, connect gene expression to chromosome structure, and contribute to human disease. PMID: 21414485 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Autologous cultured epidermis: industrialization of regenerative medicine. Nippon Yakurigaku Zasshi. 2011 Mar;137(3):150-3 Authors: Inoie M, Ozawa Y PMID: 21415565 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Research training in plastic surgery. J Craniofac Surg. 2011 Mar;22(2):383-4 Authors: Levi B, Longaker MT PMID: 21415623 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | The use of platelet gel in postero-lateral fusion: preliminary results in a series of 14 cases. Eur Spine J. 2011 Mar 17; Authors: Landi A, Tarantino R, Marotta N, Ruggeri AG, Domenicucci M, Giudice L, Martini S, Rastelli M, Ferrazza G, De Luca N, Tomei G, Delfini R Over the last few years, some hemocomponents have been used advantageously in clinical neurosurgical practice, not systemically via transfusion but topically as a sealant (fibrin glue). This has diverted the attention of many authors to the role of platelets in the healing process. The combination of hyper-concentrated platelets and fibrin glue (fibrinogen, XIII factor, fibronectin) with activated thrombin produces a platelet gel that can be easily applied to "difficult" wounds. This topical use of hemocomponents has gained an important role in regenerative medicine. The authors have considered the possibility of using a preparation with a high autologous platelet concentration applied in addition to autologous bone during vertebral postero-lateral fusion. The aim of the procedure is to induce a higher rate of vertebral fusion. Between November 2007 and November 2008, 14 patients (9 men and 5 women, mean age 58.9) underwent laminectomy, vertebral stabilization and postero-lateral fusion. The number of vertebral levels involved in stabilization was: 1 in 2 patients, 2 in 5 patients, 3 in 5 patients, 4 in 1 patient and 5 in 1 patient. Platelet gel was obtained by taking 16 ml of peripheral venous blood from the patient. For this procedure two patented test tubes were used for each patient, with a capacity of 8 m each. These make up the REGEN-THT(®) (Thrombocyte Harvesting Tube) system that makes it possible to obtain 8 ml of autologous platelet gel in 40-45 min. The addition of Ca gluconate and ethanol at 95% makes it possible to obtain a preparation of plasma rich in platelets and activated thrombin with a platelet concentration five times superior to the haematic one. The platelet gel is combined with fragments of autologous bone and synthetic bone during surgical operation. To allow a comparative assessment of the degree of fusion achieved with and without application of the platelet preparation in each patient, it was arbitrarily decided to use it in only one half of the operative field. All patients underwent serial CT scans 3 and 6 months after surgery as well as plain X-rays to evaluate bone fusion. The reconstructed CT images, especially in sagittal and axial planes, permitted an evaluation of the degree of vertebral fusion and "bone growth". The fusion rate was calculated measuring the increment of bone density on CT images, by means of an evaluation of the ROI (HU) in the newly formed bone, and comparing bone density within the bone callus formed by autologous and synthetic bone alone in the one to which the platelet preparation had been added. A good rate of fusion was observed in all patients. Furthermore, a comparative analysis of ROI at 3 and 6 months after surgery demonstrated a high increase in the fusion rate during the first 3 months after surgery. After 6 months the differences in ROI between the two sides had balanced out. However, at 6-month follow-up examination, bone density in the half of the surgical field in which platelet gel had been added to autologous-heterologous bone was higher in comparison to the contralateral one. Bony neoformation after posterior-lateral arthrodesis is well-evident 3 months after surgery and usually continues gradually for the following 18-24 months. The autologous platelet preparation used seems to accelerate bony deposition and to promote tissue healing, increasing bone density at the level of posterior-lateral arthrodesis. Moreover, this preparation has low production costs and is easy to apply. PMID: 21416280 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Novel melt-processable chitosan-polybutylene succinate fibre scaffolds for cartilage tissue engineering. J Biomater Sci Polym Ed. 2011;22(4-6):773-88 Authors: Oliveira JT, Crawford A, Mundy JL, Sol PC, Correlo VM, Bhattacharya M, Neves NM, Hatton PV, Reis RL Novel chitosan/polybutylene succinate fibre-based scaffolds (C-PBS) were seeded with bovine articular chondrocytes in order to assess their suitability for cartilage tissue engineering. Chondrocytes were seeded onto C-PBS scaffolds using spinner flasks under dynamic conditions, and cultured under orbital rotation for a total of 6 weeks. Non-woven polyglycolic acid (PGA) felts were used as reference materials. Tissue-engineered constructs were characterized by scanning electron microscopy (SEM), hematoxylin-eosin (H&E), toluidine blue and alcian blue staining, immunolocalization of collagen types I and II, and dimethylmethylene blue (DMB) assay for glycosaminoglycans (GAG) quantification at different time points. SEM showed the chondrocytes' typical morphology, with colonization at the surface and within the pores of the C-PBS scaffolds. These observations were supported by routine histology. Toluidine blue and alcian blue stains, as well as immunohistochemistry for collagen types I and II, provided qualitative information on the composition of the engineered extracellular matrix. More pronounced staining was observed for collagen type II than collagen type I. Similar results were observed with constructs engineered on PGA scaffolds. These also exhibited higher amounts of matrix glycosaminoglycans and presented a central region which contained fewer cells and little matrix, a feature that was not detected with C-PBS constructs. PMID: 20566057 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Osteogenic differentiation of adipose-derived stromal cells in mouse and human: in vitro and in vivo methods. J Craniofac Surg. 2011 Mar;22(2):388-91 Authors: Levi B, Longaker MT PMID: 21415625 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Development and initial validation of the assessment of caregiver experience with neuromuscular disease. J Pediatr Orthop. 2011 Apr-May;31(3):284-92 Authors: Matsumoto H, Clayton-Krasinski DA, Klinge SA, Gomez JA, Booker WA, Hyman JE, Roye DP, Vitale MG Orthopaedic intervention can have a wide range of functional and psychosocial effects on children with neuromuscular disease (NMD). In the multihandicapped child (Gross Motor Classification System IV/V), functional status, pain, psychosocial function, and health-related quality of life also have effects on the families of these child. The purpose of this study is to report the development and initial validation of an outcomes instrument specifically designed to assess the caregiver impact experienced by parents raising severely affected NMD children: the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND). PMID: 21415688 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Hypoxia and adipose-derived stem cell-based tissue regeneration and engineering. Expert Opin Biol Ther. 2011 Mar 18; Authors: Zachar V, Duroux M, Emmersen J, Rasmussen JG, Pennisi CP, Yang S, Fink T Introduction: Realization that oxygen is one of the key regulators of development and differentiation has a profound significance on how current cell-based and tissue engineering applications using adipose-derived stem cells (ASCs) can be further improved. Areas covered: The article provides an overview of mechanisms of hypoxic responses during physiological adaptations and development. Furthermore, a synopsis of the hypoxic responses of ASCs is provided, and this information is presented in context of their utility as a major source of stem cells across the regenerative applications explored to date. Expert opinion: The reader will obtain insight into a highly specific area of stem cell research focusing on ASCs and hypoxia. In order to enhance the level of comprehension, a broader context with other stem cell and experimental systems is provided. It is emphasized that the pericellular oxygen tension is a critical regulatory factor that should be taken into account when devising novel stem cell-based therapeutic applications along with other parameters, such as biochemical soluble factors and the growth substrates. PMID: 21413910 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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