|  |  |  | | | | | TERMSC | | | | | | | | | | | | | | | | | | | Recent progress in the therapeutic applications of nanotechnology. Curr Opin Pediatr. 2011 Apr;23(2):215-20 Authors: Solomon M, D'souza GG The field of pharmaceutical and medical nanotechnology has grown rapidly in recent decades and offers much promise for therapeutic advances. This review is intended to serve as a quick summary of the major areas in the therapeutic application of nanotechnology. PMID: 21412081 [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] | | | | | | | | | | | | | | | | | | | | | | | | | Biological approaches toward dental pulp regeneration by tissue engineering. J Tissue Eng Regen Med. 2011 Apr;5(4):e1-e16 Authors: Sun HH, Jin T, Yu Q, Chen FM Root canal therapy has been the predominant approach in endodontic treatment, wherein the entire pulp is cleaned out and replaced with a gutta-percha filling. However, living pulp is critical for the maintenance of tooth homeostasis and essential for tooth longevity. An ideal form of therapy, therefore, might consist of regenerative approaches in which diseased/necrotic pulp tissues are removed and replaced with regenerated pulp tissues to revitalize the teeth. Dental pulp regeneration presents one of the most challenging issues in regenerative dentistry due to the poor intrinsic ability of pulp tissues for self-healing and regrowth. With the advent of modern tissue engineering and the discovery of dental stem cells, biological therapies have paved the way to utilize stem cells, delivered or internally recruited, to generate dental pulp tissues, where growth factors and a series of dentine extracellular matrix molecules are key mediators that regulate the complex cascade of regeneration events to be faithfully fulfilled. Copyright © 2010 John Wiley & Sons, Ltd. PMID: 21413154 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Evaluation of senescence in mesenchymal stem cells isolated from equine bone marrow, adipose tissue and umbilical cord tissue. Stem Cells Dev. 2011 Mar 16; Authors: Vidal M, Walker NJ, Napoli E, Borjesson DL Mesenchymal stem cells (MSCs) from adult and neonatal tissues are intensively investigated for their use in regenerative medicine. The purpose of this study was to compare the onset of replicative senescence in MSCs isolated from equine bone marrow (BMSC), adipose tissue (ASC) and umbilical cord tissue (UCMSC). MSC proliferation (cell doubling), senescence associated β-galactosidase staining, telomere length, Sox-2 and lineage-specific marker expression were assessed for MSCs harvested from tissues of 4 different donors. The results show that before senescence ensued, all cell types proliferated at approximately 1 day/cell doubling. BMSCs significantly increased population doubling rate by passage 10 and ceased proliferation after a little more than 30 total population doublings while UCMSCs and ASCs achieved about 60 to 80 total population doublings. UCMSC and ASCs showed marked β- galactosidase staining after approximately 70 population doublings while BMSCs stained positive by approximately 30 population doublings. The onset of senescence was associated with significant reduction in telomere length averaging 10.2 kbp at passage 3 and 4.5 kbp in senescent cultures. MSCs stained intensively for osteonectin at senescence compared to earlier passages, while vimentin and low levels of smooth muscle actin were consistently expressed. Sox-2 gene expression was consistently noted in all three MSC types. In conclusion, equine BMSCs appear to senesce much earlier than ASCs and UCMSCs. These results demonstrate the limited passage numbers of subcultured BMSCs available for use in research and tissue engineering and suggest that adipose tissue and umbilical cord tissue may be preferable for tissue banking purposes. PMID: 21410356 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Application of conductive polymers, scaffolds and electrical stimulation for nerve tissue engineering. J Tissue Eng Regen Med. 2011 Apr;5(4):e17-35 Authors: Ghasemi-Mobarakeh L, Prabhakaran MP, Morshed M, Nasr-Esfahani MH, Baharvand H, Kiani S, Al-Deyab SS, Ramakrishna S Among the numerous attempts to integrate tissue engineering concepts into strategies to repair nearly all parts of the body, neuronal repair stands out. This is partially due to the complexity of the nervous anatomical system, its functioning and the inefficiency of conventional repair approaches, which are based on single components of either biomaterials or cells alone. Electrical stimulation has been shown to enhance the nerve regeneration process and this consequently makes the use of electrically conductive polymers very attractive for the construction of scaffolds for nerve tissue engineering. In this review, by taking into consideration the electrical properties of nerve cells and the effect of electrical stimulation on nerve cells, we discuss the most commonly utilized conductive polymers, polypyrrole (PPy) and polyaniline (PANI), along with their design and modifications, thus making them suitable scaffolds for nerve tissue engineering. Other electrospun, composite, conductive scaffolds, such as PANI/gelatin and PPy/poly(ε-caprolactone), with or without electrical stimulation, are also discussed. Different procedures of electrical stimulation which have been used in tissue engineering, with examples on their specific applications in tissue engineering, are also discussed. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21413155 [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] | | | | | | | | | | | | | | | | | | | | | | | | | Crosslink effect and albumin adsorption onto chitosan/alginate multilayered systems: an in situ QCM-D study. Macromol Biosci. 2010 Dec 8;10(12):1444-55 Authors: Martins GV, Merino EG, Mano JF, Alves NM The adsorption of HSA onto CHI/ALG multilayer assemblies was assessed in situ using QCM-D. It was found that the behavior of HSA on biomaterials surface can be tuned by adjusting parameters of the polyelectrolyte system such as pH, layer number, crosslinker and polymer terminal layer. Our results confirmed the key role of electrostatic interactions during HSA adsorption, since oppositely charged surfaces were more effective in promoting protein adhesion. QCM-D data revealed that crosslinking (CHI/ALG)(5) CHI films allows HSA to become adsorbed in physiological conditions. Our results suggested that the biological potential of biopolymers and the mild conditions of the LbL technique turn these natural nanoassemblies into a suitable choice to be used as pH-sensitive coatings. PMID: 21125694 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Enhanced differentiation of embryonic and neural stem cells to neuronal fates on laminin peptides doped polypyrrole. Macromol Biosci. 2010 Dec 8;10(12):1456-64 Authors: Zhang L, Stauffer WR, Jane EP, Sammak PJ, Cui XT PPy is a conducting polymer material that has been widely investigated for biomedical applications. hESCs and adult rNSCs were grown on four PPy surfaces doped with PSS or peptide from laminin (p20, p31, and a mixture of p20 and p31) respectively. After 7 d, both PPy/p20 and PPy/p31 promoted neuroectoderm formation from hESCs. After 14 d of culture, surfaces containing p20 showed the highest percentage of neuronal differentiation from hESC, while the PPy/p31 surface showed better cell attachment and spreading. In rNSCs cultures, a higher percentage of neurons were found on the PPy/p20 surface than other surfaces at 7 and 14 d. For differentiated neurons, p20 promoted both the primary and total neurite outgrowth. Longer primary neurites were found on p20-containing surfaces and a longer total neurite length was found on PPy/p20 surface. These results demonstrated that, by doping PPy with different bioactive peptides, differentiation of stem cells seeded at different stages of development is affected. PMID: 20954199 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | State of the art and future perspectives of articular cartilage regeneration: a focus on adipose-derived stem cells and platelet-derived products. J Tissue Eng Regen Med. 2011 Apr;5(4):e36-51 Authors: Hildner F, Albrecht C, Gabriel C, Redl H, van Griensven M Trauma, malposition and age-related degeneration of articular cartilage often result in severe lesions that do not heal spontaneously. Many efforts over the last centuries have been undertaken to support cartilage healing, with approaches ranging from symptomatic treatment to structural cartilage regeneration. Microfracture and matrix-associated autologous chondrocyte transplantation (MACT) can be regarded as one of the most effective techniques available today to treat traumatic cartilage defects. Research is focused on the development of new biomaterials, which are intended to provide optimized physical and biochemical conditions for cell proliferation and cartilage synthesis. New attempts have also been undertaken to replace chondrocytes with cells that are more easily available and cause less donor site morbidity, e.g. adipose derived stem cells (ASC). The number of in vitro studies on adult stem cells has rapidly increased during the last decade, indicating that many variables have yet to be optimized to direct stem cells towards the desired lineage. The present review gives an overview of the difficulties of cartilage repair and current cartilage repair techniques. Moreover, it reviews new fields of cartilage tissue engineering, including stem cells, co-cultures and platelet-rich plasma (PRP). Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21413156 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Study on the biological characteristics of adipose stem cells derived from renal adipose capsule cultured in vitro]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2010 Nov;26(11):1078-81 Authors: Wu W, Zheng HG, Zhang DW, Mei YM To investigate the culture conditions and biological characteristics of the adipose-derived stem cells (ADSCs) isolated from renal adipose capsule so as to find a better source of stem cells for the treatment of kidney disease. PMID: 21055345 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Future therapeutical strategies dictated by pre-clinical evidence in ALS. Arch Ital Biol. 2011 Mar;149(1):169-74 Authors: Fornai F, Meininger V, Silani V Classic concepts on amyotrophic lateral sclerosis led to definethe disease as a selective degeneration of upper and lower motor neurons. At present such selectivity is questioned by novel findings. For instance, the occurrence offrontotemporal dementia is now increasingly recognized in the course of ALS. Again, areas outside the central nervous system are targeted in ALS. In keeping with motor areas other cell types surrounding motor neurons such asglia and interneurons are key in the pathogenesis of ALS. This multiple cell involvement may be due to a prion-like diffusion of specific misfolded proteins which are altered in ALS. This is the case of FUS and TDP-43 which harbor a prion domain prone to pathological misfolding. These misfolded proteins are metabolized by the autophagy, but in ALS there is evidence for a specific deficit of autophagy which impedes the clearance of these proteins. These concepts lead to re-analyze the potential therapeutics of ALS. In fact, mere cell substitution (stem cell) therapy appears insufficient to contrast all the alterations in the various pathways affected by ALS. Although preclinical data speed the application of stem cells in human clinical trials, several hurdles limit their translation into new therapies. Future treatments are expected to consider the need to target both motor neurons and neighboring cells which may contribute to the diffusion and persistence of the disease. On this basis the present manuscript describes which future strategies need to be pursued in order to design optimal therapeutic trial in ALS. PMID: 21412723 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | BMP-12 Treatment of Adult Mesenchymal Stem Cells In Vitro Augments Tendon-Like Tissue Formation and Defect Repair In Vivo. PLoS One. 2011;6(3):e17531 Authors: Lee JY, Zhou Z, Taub PJ, Ramcharan M, Li Y, Akinbiyi T, Maharam ER, Leong DJ, Laudier DM, Ruike T, Torina PJ, Zaidi M, Majeska RJ, Schaffler MB, Flatow EL, Sun HB We characterized the differentiation of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) into tenocyte-like cells in response to bone morphogenetic protein-12 (BMP-12). BM-MSCs were prepared from Sprague-Dawley rats and cultured as monolayers. Recombinant BMP-12 treatment (10 ng/ml) of BM-MSCs for 12 hours in vitro markedly increased expression of the tenocyte lineage markers scleraxis (Scx) and tenomodulin (Tnmd) over 14 days. Treatment with BMP-12 for a further 12-hour period had no additional effect. Colony formation assays revealed that ∼80% of treated cells and their progeny were Scx- and Tnmd-positive. BM-MSCs seeded in collagen scaffolds and similarly treated with a single dose of BMP-12 also expressed high levels of Scx and Tnmd, as well as type I collagen and tenascin-c. Furthermore, when the treated BM-MSC-seeded scaffolds were implanted into surgically created tendon defects in vivo, robust formation of tendon-like tissue was observed after 21 days as evidenced by increased cell number, elongation and alignment along the tensile axis, greater matrix deposition and the elevated expression of tendon markers. These results indicate that brief stimulation with BMP-12 in vitro is sufficient to induce BM-MSC differentiation into tenocytes, and that this phenotype is sustained in vivo. This strategy of pretreating BM-MSCs with BMP-12 prior to in vivo transplantation may be useful in MSC-based tendon reconstruction or tissue engineering. PMID: 21412429 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Vörner type palmoplantar keratoderma: novel KRT9 mutation associated with knuckle pad-like lesion and recurrent mutation causing digital mutilation. Br J Dermatol. 2011 Mar 17; Authors: Umegaki N, Nakano H, Tamai K, Mitsuhashi Y, Akasaka E, Sawamura D, Katayama I PMID: 21410681 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | Novel Strategies in Immunosuppression: Issues in Perspective. Transplantation. 2011 Mar 15; Authors: Webber A, Hirose R, Vincenti F Recent findings suggest that a chronic alloimmune response is playing the dominant role in late allograft loss, challenging the notion that most grafts are lost due to the inexorable progression of calcineurin inhibitor (CNI) nephrotoxicity. CNIs have failed to improve long-term outcomes and are associated with multiple metabolic derangements. Thus, improvement in long-term allograft outcomes may depend on new agents with novel mechanisms of action, devoid of the toxicities associated with CNIs. To meet this need, inhibitors of novel pathways in B cell and plasma cell activation have emerged to combat the humoral immune response including belimumab and atacicept, both promising targets of B-cell survival factors and bortezomib and eculizumab, agents currently in trials for desensitization protocols and treatment of antibody-mediated rejection. Promising agents for maintenance immunosuppression, used as monotherapy or synergistically, include monoclonal antibodies and fusion receptor proteins targeting the CD40-CD154 pathway (multiple anti-CD40 antibodies), the CD28-CD80/86 pathway (i.e., belatacept), the LFA3-CD2 pathway (i.e., alefacept), and small molecules such as tofacitinib, a janus kinase 1/3 inhibitor. The induction of allograft tolerance has been attempted with some success with simultaneous bone marrow/kidney transplantation from the same donor, albeit, limited by its associated toxicites. Finally, the exciting fields of tissue engineering and stem cell biology with the repopulation of decellularized organs is ushering in a new paradigm for transplantation. The era of simplified immunosuppression regimens devoid of toxicities is upon us with the promise of dramatic improvement in long term survival. PMID: 21412186 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | Type I collagen, fibrin and PuraMatrix matrices provide permissive environments for human endothelial and mesenchymal progenitor cells to form neovascular networks. J Tissue Eng Regen Med. 2011 Apr;5(4):e74-86 Authors: Allen P, Melero-Martin J, Bischoff J The field of tissue engineering seeks to create metabolically demanding, functional tissues, which will require blood vessel networks capable of forming rapidly in a variety of extracellular matrix (ECM) environments. We tested whether human endothelial progenitor cells (EPCs) and mesenchymal progenitor cells (MPCs) could form microvascular networks in type I collagen, fibrin and an engineered peptide hydrogel, PuraMatrix, in 7 days in vivo in immune-deficient mice. These results are compared to those previously published, based on the Matrigel ECM. Perfused blood vessels formed in all three types of ECM within 7 days. Collagen at 5 and 6 mg/ml and 10 mg/ml fibrin supported vessel formation at 30-60 vessels/mm(2) , and PuraMatrix enabled vessel formation to 160 vessels/mm(2) , significantly greater than collagen or fibrin. Vessels were composed of EPCs with perivascular cells on their abluminal surfaces. EPCs injected alone formed a low density of blood vessels in collagen and PuraMatrix, while MPCs injected alone resulted in sparse vessel networks in all ECMs tested. A rheometer was used to determine whether the ECMs which supported vascularization had bulk physical properties similar to or distinct from Matrigel. Collagen and fibrin were the stiffest matrices to support extensive vascularization, with storage moduli in the range 385-510 Pa, while Matrigel, at 80 Pa, and PuraMatrix, at 5 Pa, were far more compliant. Thus, EPCs and MPCs were capable of vasculogenesis in environments having disparate physical properties, although vascular density was greater in more compliant ECMs. We propose that EPC/MPC-mediated vascularization is a versatile technology which may enable the development of engineered organs. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21413157 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | Research training in plastic surgery. J Craniofac Surg. 2011 Mar;22(2):383-4 Authors: Levi B, Longaker MT PMID: 21415623 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |  | |  | |  |
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