|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Co-culture of mesenchymal-like stromal cells derived from human foreskin permits long term propagation and differentiation of human embryonic stem cells. J Cell Biochem. 2011 Feb 17; Authors: Mamidi MK, Pal R, Mori NA, Arumugam G, Thrichelvam ST, Noor PJ, Abdullah HM, Gupta PK, Das AK, Zakaria Z, Bhonde R Among the different parameters governing the successful derivation and expansion of human embryonic stem cells (hESC), feeder layers play the most important role. Human feeders in form of human mesenchymal stromal cells (hMSCs) and human foreskin fibroblasts (HFFs) lay the foundation for eradication of animal-derived hESC culture system. In this study we explored the potential of human foreskin derived mesenchymal like stromal cells (HF-MSCs) to support self renewal and pluripotency of hESC. The MSCs isolated from human foreskin were found to be resistant to standard concentrations and duration of mitomycin-C treatment. Growth pattern, gene profiling (Oct-4, Nanog, Sox-2, Rex-1), cytoskeletal protein expression (vimentin, nestin) and tri-lineage differentiation potential into adipocytes, chondrocytes and osteocytes confirmed their mesenchymal stromal cell status. Further, the HF-MSCs were positive for CD105, CD166, CD73, CD44, CD90, SSEA-4 and negative for CD34, CD45, HLA-DR cell-surface markers and were found to exhibit BM-MSC-like characteristics. hESC lines co-cultured with HF-MSC feeders showed expression of expected pluripotent transcription factors Oct-4, Nanog, Sox-2, GDF-3, Rex-1, STELLAR, ABCG2, Dppa5, hTERT; surface markers SSEA-4, TRA-1-81 and maintained their cytogenetic stability during long term passaging. These novel feeders also improved the formation of embryoid bodies (EBs) from hESC which produced cell types representing three germ layers. This culture system has the potential to aid the development of clinical-grade hESCs for regenerative medicine and drug screening. Further, we envisage foreskin can serve as a valuable source of alternative MSCs for specific therapeutic applications. J. Cell. Biochem. © 2011 Wiley-Liss, Inc. PMID: 21337383 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Smurfs have "fused" into the asymmetric division of stem cells. Protein Cell. 2011 Jan;2(1):2-4 Authors: Cheng SY, Zhang YE PMID: 21337003 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Cranioplasty with adipose-derived stem cells and biomaterial. A novel method for cranial reconstruction. Neurosurgery. 2011 Feb 16; Authors: Thesleff T, Lehtimäki K, Niskakangas T, Mannerström B, Miettinen S, Suuronen R, Ohman J BACKGROUND:: There is no optimal method for reconstruction of large calvarial defects. Because of the limitations of autologous bone grafts and alloplastic materials, new methods for performing cranioplasties are needed. OBJECTIVE:: To create autologous bone to repair skull deficits. METHODS:: We performed a cranioplasty procedure with this new method for four patients who had large calvarial defects of different etiologies. We used autologous adipose-derived stem cells (auto ASCs) seeded in beta-tricalcium phosphate (betaTCP) granules. For two patients we used bilaminate technique with resorbable meshes. RESULTS:: During the follow up period there were no clinically relevant post-operative complications. The CT scans revealed satisfactory outcome in ossification and in the clinical examinations the outcomes were good. The Hounsfield Unit (HU) of the cranioplasty was measured from each CT. The HU increased gradually to meet the value of bone. CONCLUSION:: The combination of scaffold material such as betaTCP and autologous adipose derived stem cells constitutes a promising model for reconstruction of human large cranial defects. The success of these clinical cases paves way for further studies and clinical applications to turn this method into a reliable treatment regimen. PMID: 21336223 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The low viability of human CD34+ cells under acidic conditions is improved by exposure to thrombopoietin, stem cell factor, interleukin-3, or increased cyclic adenosine monophosphate levels. Transfusion. 2011 Feb 18; Authors: D'Atri LP, Etulain J, Romaniuk MA, Torres O, Negrotto S, Schattner M BACKGROUND: Transplanted hematopoietic progenitor cells (CD34+) have shown great promise in regenerative medicine. However, the therapeutic potential of transplanted cells is limited by their poor viability. It is well known that the microenvironment in which progenitors reside substantially affects their behavior. Because extracellular acidosis is a common feature of injured tissues or the tumor microenvironment and is a critical regulator of cell survival and activation, we evaluated the impact of acidosis on CD34+ cell biology. STUDY DESIGN AND METHODS: Apoptosis was evaluated by fluorescence microscopy and binding of annexin V, hypodiploid cells, Bcl-xL expression, active caspase-3, and mitochondrial membrane potential was determined by flow cytometry. Colony-forming units were studied by clonogenic assays, and cell cycle was evaluated by flow cytometry. RESULTS: Exposure of CD34+ cells to low pH (7.0-6.5) caused intracellular acidification, decreased cell proliferation, and triggered apoptosis via the mitochondrial pathway. Whereas exposure to thrombopoietin (TPO), stem cell factor (SCF), interleukin (IL)-3 or increases in cyclic adenosine monophosphate (cAMP) levels prevented CD34+ cell death induced by acidic conditions, granulocyte-macrophage-colony-stimulating factor, FMS-like tyrosine kinase 3-ligand, erythropoietin, and vascular endothelial growth factor had no effect. Despite their cytoprotective effect, CD34+ cell expansion triggered by TPO, SCF, or IL-3 was significantly impaired at low pH. However, a cocktail of these three cytokines synergistically supported proliferation, cell cycle progression, and colony formation. DISCUSSION: Our findings indicate that an acidic milieu is deleterious for CD34+ cells and that a combination of certain cytokines and cAMP donors may improve cell viability and function. These data may be useful to develop new therapeutic strategies or to optimize protocols for regenerative medicine. PMID: 21332728 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mitochondrial peptidase IMMP2L mutation causes early onset of age-associated disorders and impairs adult stem cell self-renewal. Aging Cell. 2011 Feb 18; Authors: George SK, Jiao Y, Bishop CE, Lu B Mitochondrial reactive oxygen species (ROS) are proposed to play a central role in aging and age-associated disorders, although direct in vivo evidence is lacking. We recently generated a mouse mutant with mutated Inner Mitochondrial Membrane Peptidase 2-like (Immp2l) gene, which impairs the signal peptide sequence processing of mitochondrial proteins cytochrome c1 and glycerol phosphate dehydrogenase 2. The mitochondria from mutant mice generate elevated levels of superoxide ion and cause impaired fertility in both sexes. Here we design experiments to examine the effects of excessive mitochondrial ROS generation on health span. We show that Immp2l mutation increases oxidative stress in multiple organs such as the brain and the kidney, although expression of superoxide dismutases in these tissues of the mutants is also increased. The mutants show multiple aging-associated phenotypes, including wasting, sarcopenia, loss of subcutaneous fat, kyphosis and ataxia, with female mutants showing earlier onset and more severe age-associated disorders than male mutants. The loss of body weight and fat was unrelated to food intake. Adipose derived stromal cells (ADSC) from mutant mice showed impaired proliferation capability, formed significantly less and smaller colonies in colony formation assays, although they retained adipogenic differentiation capability in vitro. This functional impairment was accompanied by increased levels of oxidative stress. Our data showed that mitochondrial ROS is the driving force of accelerated aging and suggested that ROS damage to adult stem cells could be one of the mechanisms for age-associated disorders. PMID: 21332923 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Autologous skin cell spray-transplantation for a deep dermal burn patient in an ambulant treatment room setting. Burns. 2011 Feb 18; Authors: Gerlach JC, Johnen C, McCoy E, Bräutigam K, Plettig J, Corcos A PMID: 21334816 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Current perspective of pathophysiological and interventional effects on endothelial progenitor cell biology: focus on PI3K/AKT/eNOS pathway. Int J Cardiol. 2010 Oct 29;144(3):350-66 Authors: Everaert BR, Van Craenenbroeck EM, Hoymans VY, Haine SE, Van Nassauw L, Conraads VM, Timmermans JP, Vrints CJ For more than a decade, endothelial progenitor cells (EPCs) have been implicated in cardiovascular homeostasis. EPCs are believed to reside within the bone marrow in close contact with surrounding stromal cells, and, under stimulation of pro-inflammatory cytokines, EPCs are mobilized out of the bone marrow. Hereafter circulating EPCs home to peripheral tissues, undergoing further proliferation and differentiation. Under certain pathophysiologic conditions this process seems to be blunted, resulting in a reduced capacity of EPCs to engage in vasculogenesis at sites of endothelial injury or tissue ischemia. In this review, we focus on the effects of traditional cardiovascular risk factors on EPC biology and we explore whether pharmacological, dietary and lifestyle interventions can favorably restore EPC mobilization, differentiation, homing and angiogenic properties. Because the PI3K/Akt/eNOS pathway plays a pivotal role in the process of EPC mobilization, migration and homing, we specifically emphasize the involvement of PI3K, Akt and eNOS in EPC biology under these different (patho)physiologic conditions. (Pre)clinically used drugs or lifestyle interventions that have been shown to ameliorate EPC biology are reviewed. These treatment strategies remain attractive targets to restore the regenerative capacity of EPCs in cardiovascular diseases. PMID: 20444511 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Decellularized matrices for tissue engineering. Expert Opin Biol Ther. 2010 Dec;10(12):1717-28 Authors: Hoshiba T, Lu H, Kawazoe N, Chen G Biomimetic scaffolds and substrates of extracellular matrices (ECMs) play an important role in the regulation of cell function and in the guidance of new tissue regeneration, as an ECM has the intrinsic cues necessary to communicate with and dictate to cells. PMID: 21058932 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | From kidney development to drug delivery and tissue engineering strategies in renal regenerative medicine. J Control Release. 2011 Feb 17; Authors: Dankers PY, Boomker JM, Meijer EW, Popa ER, van Luyn MJ Deterioration of renal function is typically slow but progressive, and therefore renal disease is often diagnosed in a late stage when already serious complaints occur. Ultimately when renal function has dropped below 10%, renal replacement is required. Renal transplantation provides a long-term solution but due to shortage of donor kidneys most patients receive hemodialysis therapy. Although hemodialysis is an effect method to correct disturbances in water and electrolyte balances in the body, it does not substitute for the important endocrine and metabolic renal functions that are critical for homeostasis. Among these functions are, the renal production of renin which controls blood pressure, the secretion of erythropoietin which stimulates the synthesis of red blood cells, and the excretion of protein bound waste products. As a consequence, many dialysis patients remain in poor health. With the development of regenerative medicine, and particularly tissue engineering and novel drug delivery strategies, alternative routes for renal replacement are emerging. Increasing understanding of (stem) cells, growth factors and regeneration in the kidney has contributed to a whole new view on restoration and reconstruction of (parts of) renal tissue that may be used to improve current renal replacement therapies. Here, an overview of critical interactions between cells, growth factors and extracellular matrix molecules in kidney development and regeneration will be described. Ultimately, we will discuss how these interactions can be translated to strategies for in-vivo regeneration and in-vitro reconstruction of the kidney. PMID: 21334390 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cryopreservation of amniotic fluid-derived stem cells using natural cryoprotectants and low concentrations of dimethylsulfoxide. Cryobiology. 2011 Feb 15; Authors: Seo JM, Sohn MY, Suh JS, Atala A, Yoo JJ, Shon YH Amniotic fluid-derived stem cells (AFSCs) are a potential cell source for therapeutic applications. They can be easily mass produced, cryopreserved and shipped to clinics for immediate use. However, one major obstacle to the manufacturing of clinical grade stem cells is the need for current good manufacturing practices for cryopreservation, storage, and distribution of these cells. Most current cryopreservation methods used for stem cells include the potentially toxic cryoprotectant (CPA) dimethylsulfoxide (Me(2)SO) in the presence of animal serum proteins that prevent direct use of these cells in human therapeutic applications. To avoid any potential cryoprotectant related complications, it will be essential to develop non-toxic CPAs or reduce CPA concentration in the freezing media used. In this study, we assessed the use of disaccharides, antioxidants and caspase inhibitors for cryopreservation of AFSCs in combination with a reduced concentration of Me(2)SO. The thawed cells were tested for viability with MTT assays and a growth curve was created to measure population doubling time. In addition, we performed flow cytometry analysis for cell surface antigens, RT-PCR for mRNA expression of stem cell markers, and assays to determine the myogenic differentiation potential of the cells. A statistically significant (p<0.05) increase in post-thawed cell viability in solutions containing trehalose, catalase and zVAD-fmk with 5% Me(2)SO was observed. The solutions containing trehalose and catalase with 5% or 2.5% (v/v) Me(2)SO produced results similar to those for the control (10% (v/v) Me(2)SO and 30% FBS) in terms of culture growth, expression of cell surface antigens and mRNA expression of stem cell markers in AFSCs cryopreserved for a minimum of 3 weeks. Thus, AFSCs can be cryopreserved with 1/4 the standard Me(2)SO concentration with the addition of disaccharides, antioxidants and caspase inhibitors. The use of Me(2)SO at low concentrations in cell freezing solutions may support the development of clinical trials of AFSCs. PMID: 21335000 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effect of freeze-drying on the mechanical, physical and morphological properties of glutaraldehyde-treated bovine pericardium: evaluation of freeze-dried treated bovine pericardium properties. J Appl Biomater Biomech. 2010 September-December;8(3):186-190 Authors: Borgognoni CF, Maizato MJ, Leirner AA, Polakiewicz B, Beppu MM, Higa OZ, Pitombo RN Purpose: Biomaterials have been widely used in the field of regenerative medicine. Bovine pericardium tissue has been successfully used as a bioprosthetic material in manufacturing heart valves, but studies concerning the tissue are ongoing in order to improve its storage, preservation and transportation. This article provides an overview of the characteristics of bovine pericardium tissue chemically treated after the freeze-drying process. These characteristics are essential to evaluate the changes or damage to the tissue during the process. Methods: The mechanical properties of the tissue were analyzed by three different methods due to its anisotropic characteristics. The physical properties were analyzed by a colorimetric method, while the morphological properties were evaluated by scanning electron microscopy (SEM). Results: The freeze-dried bovine pericardium showed no significant change in its mechanical properties. There was no significant change in the elasticity of the tissue (p>0.05) and no color change. In addition, SEM analysis showed that the freeze-dried samples did not suffer structural collapse. Conclusions: It was concluded that glutaraldehyde-treated bovine pericardium tissue showed no significant change in its properties after the freeze-drying process. PMID: 21337310 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Response To Moulder Et Al: Re: Davis Et Al. [Exp Hematol. 2010;38:270-281]. Exp Hematol. 2011 Feb 15; Authors: Davis TA, Landauer MR, Mog SR, Barshishat-Kupper M, Zins SR, Amare MF, Day RM PMID: 21335054 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Wound healing and regenerative strategies. Oral Dis. 2011 Jan 7; Authors: Nauta A, Gurtner G, Longaker M Oral Diseases (2011) doi: 10.1111/j.1601-0825.2011.01787.x Wound healing is a complex biological process that affects multiple tissue types. Wounds in the oral cavity are particularly challenging given the variety of tissue types that exist in close proximity to one another. The goal of regenerative medicine is to facilitate the rapid replacement of lost or damaged tissue with tissue that is functional, and physiologically similar to what previously existed. This review provides a general overview of wound healing and regenerative medicine, focusing specifically on how recent advances in the fields of stem cell biology, tissue engineering, and oral disease could translate into improved clinical outcomes. PMID: 21332599 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Proteomics: a reality-check for putative stem cells. Circ Res. 2011 Feb 18;108(4):499-511 Authors: Prokopi M, Mayr M The concept of using stem cells for cardiovascular repair holds great potential, but uncertainties in preclinical experiments must be addressed before their therapeutic application. Contemporary proteomic techniques can help to characterize cell preparations more thoroughly and identify some of the potential causes that may lead to a high failure rate in clinical trials. The first part of this review discusses the broader application of proteomics to stem cell research by providing an overview of the main proteomic technologies and how they might help the translation of stem cell therapy. The second part focuses on the controversy about endothelial progenitor cells (EPCs) and raises cautionary flags for marker assignment and assessment of cell purity. A proteomics-led approach in early outgrowth EPCs has already raised the awareness that markers used to define their endothelial potential may arise from an uptake of platelet proteins. A platelet microparticle-related transfer of endothelial characteristics to mononuclear cells can result in a misinterpretation of the assay. The necessity to perform counterstaining for platelet markers in this setting is not fully appreciated. Similarly, the presence of platelets and platelet microparticles is not taken into consideration when functional improvements are directly attributed to EPCs, whereas saline solutions or plain medium serve as controls. Thus, proteomics shed new light on the caveats of a common stem cell assay in cardiovascular research, which might explain some of the inconsistencies in the field. PMID: 21335432 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Chondrogenesis of human mesenchymal stem cells mediated by the combination of SOX trio SOX5, 6, and 9 genes complexed with PEI-modified PLGA nanoparticles. Biomaterials. 2011 Feb 16; Authors: Park JS, Yang HN, Woo DG, Jeon SY, Do HJ, Lim HY, Kim JH, Park KH Target gene transfection for desired cell differentiation has recently become a major issue in stem cell therapy. For the safe and stable delivery of genes into human mesenchymal stem cells (hMSCs), we employed a non-viral gene carrier system such as polycataionic polymer, poly(ethyleneimine) (PEI), polyplexed with a combination of SOX5, 6, and 9 fused to green fluorescence protein (GFP), yellow fluorescence protein (YFP), or red fluorescence protein (RFP) coated onto PLGA nanoparticles. The transfection efficiency of PEI-modified PLGA nanoparticle gene carriers was then evaluated to examine the potential for chondrogenic differentiation by carrying the exogenous SOX trio (SOX5, 6, and 9) in hMSCs. Additionally, use of PEI-modified PLGA nanoparticle gene carriers was evaluated to investigate the potential for transfection efficiency to increase the potential ability of chondrogenesis when the trio genes (SOX5, 6, and 9) polyplexed with PEI were delivered into hMSCs. SOX trio complexed with PEI-modified PLGA nanoparticles led to a dramatic increase in the chondrogenesis of hMSCs in in vitro culture systems. For the PEI/GFP and PEI/SOX5, 6, and 9 genes complexed with PLGA nanoparticles, the expressions of GFP as reporter genes and SOX9 genes with PLGA nanoparticles showed 80% and 83% of gene transfection ratios into hMSCs two days after transfection, respectively. PMID: 21333351 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Differentiation of Dental Pulp Stem Cells Into Islet Like Aggregates. J Dent Res. 2011 Feb 18; Authors: Govindasamy V, Ronald VS, Abdullah AN, Ganesan Nathan KR, Ab Aziz ZA, Abdullah M, Musa S, Abu Kasim NH, Bhonde RR The post-natal dental pulp tissue contains a population of multipotent mesenchymal progenitor cells known as dental pulp stromal/stem cells (DPSCs), with high proliferative potential for self-renewal. In this investigation, we explored the potential of DPSCs to differentiate into pancreatic cell lineage resembling islet-like cell aggregates (ICAs). We isolated, propagated, and characterized DPSCs and demonstrated that these could be differentiated into adipogenic, chondrogenic, and osteogenic lineage upon exposure to an appropriate cocktail of differentiating agents. Using a three-step protocol reported previously by our group, we succeeded in obtaining ICAs from DPSCs. The identity of ICAs was confirmed as islets by dithiozone-positive staining, as well as by expression of C-peptide, Pdx-1, Pax4, Pax6, Ngn3, and Isl-1. There were several-fold up-regulations of these transcription factors proportional to days of differentiation as compared with undifferentiated DPSCs. Day 10 ICAs released insulin and C-peptide in a glucose-dependent manner, exhibiting in vitro functionality. Our results demonstrated for the first time that DPSCs could be differentiated into pancreatic cell lineage and offer an unconventional and non-controversial source of human tissue that could be used for autologous stem cell therapy in diabetes. PMID: 21335539 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Evaluation of intrarenal mesenchymal stem cell injection for treatment of chronic kidney disease in cats: a pilot study. J Feline Med Surg. 2011 Feb 17; Authors: Quimby JM, Webb TL, Gibbons DS, Dow SW The feasibility of autologous intrarenal mesenchymal stem cell (MSC) therapy in cats with chronic kidney disease (CKD) was investigated. Six cats (two healthy, four with CKD) received a single unilateral intrarenal injection of autologous bone marrow-derived or adipose tissue-derived MSC (bmMSC or aMSC) via ultrasound guidance. Minimum database and glomerular filtration rate (GFR) via nuclear scintigraphy were determined pre-injection, at 7 days and at 30 days post-injection. Intrarenal injection did not induce immediate or long-term adverse effects. Two cats with CKD that received aMSC experienced modest improvement in GFR and a mild decrease in serum creatinine concentration. Despite the possible benefits of intrarenal MSC injections for CKD cats, the number of sedations and interventions required to implement this approach would likely preclude widespread clinical application. We concluded that MSC could be transferred safely by ultrasound-guided intrarenal injection in cats, but that alternative sources and routes of MSC therapy should be investigated. PMID: 21334237 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Multi-potent progenitors in freshly isolated and cultured human mesenchymal stem cells: a comparison between adipose and dermal tissue. Cell Tissue Res. 2011 Feb 19; Authors: Manini I, Gulino L, Gava B, Pierantozzi E, Curina C, Rossi D, Brafa A, D'Aniello C, Sorrentino V Mesenchymal stem cells (MSCs) from human adult adipose tissue (A-MSCs) have a better differentiative ability than MSCs derived from the derma (D-MSCs). To test whether this difference is associated with differences in the content of multi-potent progenitors in A-MSCs, the number and the differentiative properties of multi-potent progenitors have been analyzed in various preparations of A-MSCs and D-MSCs. Adipogenic and osteogenic differentiation performed on colony-forming units have revealed that adipogenic and osteogenic progenitors are similar in the two populations, with only a slighty better performance of A-MSCs over D-MSCs from passages p0 to p15. An analysis of the presence of tri-, bi-, uni- and nulli-potent progenitors isolated immediately after isolation from tissues (p0) has shown comparable numbers of tri-potent and bi-potent progenitors in MSCs from the two tissues, whereas a higher content in uni-potent cells committed to adipocytes and a lower content in nulli-potent cells has been observed in A-MSCs. Furthermore, we have characterized the progenitors present in A-MSCs after six passages in vitro to verify the way in which in vitro culture can affect content in progenitor cells. We have observed that the percentage of tri-potent cells in A-MSCs at p6 remains similar to that observed at p0, although bi-potent and uni-potent progenitors committed to osteogenic differentiation increase at p6, whereas nulli-potent cells decrease at p6. These data indicate that the greater differentiative ability of A-MSC populations does not correlate directly with the number of multi-potent progenitors, suggesting that other factors influence the differentiation of bulk populations of A-MSCs. PMID: 21336533 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mitochondrial peptidase IMMP2L mutation causes early onset of age-associated disorders and impairs adult stem cell self-renewal. Aging Cell. 2011 Feb 18; Authors: George SK, Jiao Y, Bishop CE, Lu B Mitochondrial reactive oxygen species (ROS) are proposed to play a central role in aging and age-associated disorders, although direct in vivo evidence is lacking. We recently generated a mouse mutant with mutated Inner Mitochondrial Membrane Peptidase 2-like (Immp2l) gene, which impairs the signal peptide sequence processing of mitochondrial proteins cytochrome c1 and glycerol phosphate dehydrogenase 2. The mitochondria from mutant mice generate elevated levels of superoxide ion and cause impaired fertility in both sexes. Here we design experiments to examine the effects of excessive mitochondrial ROS generation on health span. We show that Immp2l mutation increases oxidative stress in multiple organs such as the brain and the kidney, although expression of superoxide dismutases in these tissues of the mutants is also increased. The mutants show multiple aging-associated phenotypes, including wasting, sarcopenia, loss of subcutaneous fat, kyphosis and ataxia, with female mutants showing earlier onset and more severe age-associated disorders than male mutants. The loss of body weight and fat was unrelated to food intake. Adipose derived stromal cells (ADSC) from mutant mice showed impaired proliferation capability, formed significantly less and smaller colonies in colony formation assays, although they retained adipogenic differentiation capability in vitro. This functional impairment was accompanied by increased levels of oxidative stress. Our data showed that mitochondrial ROS is the driving force of accelerated aging and suggested that ROS damage to adult stem cells could be one of the mechanisms for age-associated disorders. PMID: 21332923 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Fibroblasts share mesenchymal phenotypes with stem cells, but lack their differentiation and colony forming potential. Biol Cell. 2011 Feb 18; Authors: Alt E, Yan Y, Gehmert S, Song YH, Altman A, Gehmert S, Vykoukal D, Bai X Background information. Although mesenchymal stem cells and fibroblasts have been well studied, differences between these two cell types are not fully understood. We therefore comparatively analyzed antigen and gene profiles, colony-forming ability, and differentiation potential of four human cell types in vitro: commercially available skin-derived fibroblasts (hSDFs), adipose tissue-derived stem cells (hASCs), embryonic lung fibroblasts (WI38), and dermal microvascular endothelial cells (hECs). Results. hSDFs, hASCs and WI38 exhibited a similar spindle-like morphology and expressed same antigen profiles: positive for mesenchymal stem cell markers (CD44, CD73, and CD105) and fibroblastic markers (collagen I, HSP47, vimentin, FSP, and αSMA), and negative for endothelial cell marker CD31 and hematopoietic lineage markers (CD14 and CD45). We further analyzed 90 stem cell associated gene expression by performing real time PCR and found a more similar gene expression pattern between hASCs and hSDFs than between hSDFs and WI38. The expression of embryonic stem cell markers (OCT4, KLF4, NANOG, LIN28, FGF4 and REST) in hASCs and hSDFs was observed to differ more than 2.5-fold as compared with WI38. In addition, hSDFs and hASCs were capable to form colonies and differentiate into adipocytes, osteoblasts, and chondrocytes in vitro, but not WI38. Moreover, single cell-derived hSDFs and hASCs obtained by clonal expansion were able to differentiate into adipocytes and osteoblasts. However, CD31 positive hECs did not show differentiation potential. Conclusions. These findings suggest that (1) so called commercially available fibroblast preparations from skin (hSDFs) consist of a significant number of cells with differentiation potential aside from terminally differentiated fibroblasts; (2) colony-forming capacity and differentiation potential are specific important properties that discriminate mesenchymal stem cells from fibroblasts (WI38) while conventional stem cell properties such as plastic adherence and the expression of CD44, CD90 and CD105 are unspecific for stem cells. PMID: 21332447 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A randomized clinical trial comparing granulocyte-colony-stimulating factor administration sites for mobilization of peripheral blood stem cells for patients with hematologic malignancies undergoing autologous stem cell transplantation. Transfusion. 2011 Feb 18; Authors: Renfroe H, Arnold M, Vaughn L, Harvey RD, Hamilton E, Lonial S, Khoury HJ, Kaufman JL, Lechowicz MJ, Flowers CR, Waller EK BACKGROUND: A study was undertaken to investigate whether granulocyte-colony-stimulating factor (G-CSF) injection in lower adipose tissue-containing sites (arms and legs) would result in a lower exposure and reduced stem cell collection efficiency compared with injection into abdominal skin. STUDY DESIGN AND METHODS: We completed a prospective randomized study to determine the efficacy and tolerability of different injection sites for patients with multiple myeloma or lymphoma undergoing stem cell mobilization and apheresis. Primary endpoints were the number of CD34+ cells collected and the number of days of apheresis. Forty patients were randomly assigned to receive cytokine injections in their abdomen (Group A) or extremities (Group B). Randomization was stratified based on diagnosis (myeloma, n = 29 vs. lymphoma, n = 11), age, and mobilization strategy and balanced across demographic factors and body mass index. RESULTS: Thirty-five subjects were evaluable for the primary endpoint: 18 in Group A and 17 in Group B. One evaluable subject in each group failed to collect a minimum dose of at least 2.0 × 10(6) CD34+ cells/kg. The mean numbers of CD34+ cells (±SD) collected were not different between Groups A and B (9.15 × 10(6) ± 4.7 × 10(6) /kg vs. 9.85 × 10(6) ± 5 × 10(6) /kg, respectively; p = NS) after a median of 2 days of apheresis. Adverse events were not different between the two groups. CONCLUSION: The site of G-CSF administration does not affect the number of CD34+ cells collected by apheresis or the duration of apheresis needed to reach the target cell dose. PMID: 21332729 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Heparin-functionalized chitosan scaffolds for bone tissue engineering. Carbohydr Res. 2010 Dec 14; Authors: Gümüşderelioğlu M, Aday S The aim of this study is to investigate the effects of heparin-functionalized chitosan scaffolds on the activity of preosteoblasts. The chitosan scaffolds having the pore size of ∼100μm were prepared by a freeze-drying method. Two different methods for immobilization of heparin to chitosan scaffolds were successfully performed. In the first method, functionalization of the scaffolds was achieved by means of electrostatic interactions between negatively charged heparin and positively charged chitosan. The covalent immobilization of heparin to chitosan scaffolds by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDAC) and N-hydroxysuccinimide (NHS) was used as a second immobilization method. Morphology, proliferation, and differentiation of MC3T3-E1 preosteoblasts on heparin-functionalized chitosan scaffolds were investigated in vitro. The results indicate that covalently bound heparin containing chitosan scaffolds (CHC) stimulate osteoblast proliferation compared to other scaffolds, that is, unmodified chitosan scaffolds (CH), electrostatically bound heparin containing chitosan scaffolds (EHC), and CH+free heparin (CHF). SEM images also proved the stimulative effect of covalently bound heparin on the proliferation of preosteoblasts. Alkaline phosphatase (ALP) and osteocalcin (OCN) levels of cells proliferated on CHC and EHC were also higher than those for CH and CHF. In vitro studies have demonstrated that chitosan scaffolds increase viability and differentiation of MC3T3-E1 cells especially in the presence of immobilized heparin. PMID: 21333274 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | From kidney development to drug delivery and tissue engineering strategies in renal regenerative medicine. J Control Release. 2011 Feb 17; Authors: Dankers PY, Boomker JM, Meijer EW, Popa ER, van Luyn MJ Deterioration of renal function is typically slow but progressive, and therefore renal disease is often diagnosed in a late stage when already serious complaints occur. Ultimately when renal function has dropped below 10%, renal replacement is required. Renal transplantation provides a long-term solution but due to shortage of donor kidneys most patients receive hemodialysis therapy. Although hemodialysis is an effect method to correct disturbances in water and electrolyte balances in the body, it does not substitute for the important endocrine and metabolic renal functions that are critical for homeostasis. Among these functions are, the renal production of renin which controls blood pressure, the secretion of erythropoietin which stimulates the synthesis of red blood cells, and the excretion of protein bound waste products. As a consequence, many dialysis patients remain in poor health. With the development of regenerative medicine, and particularly tissue engineering and novel drug delivery strategies, alternative routes for renal replacement are emerging. Increasing understanding of (stem) cells, growth factors and regeneration in the kidney has contributed to a whole new view on restoration and reconstruction of (parts of) renal tissue that may be used to improve current renal replacement therapies. Here, an overview of critical interactions between cells, growth factors and extracellular matrix molecules in kidney development and regeneration will be described. Ultimately, we will discuss how these interactions can be translated to strategies for in-vivo regeneration and in-vitro reconstruction of the kidney. PMID: 21334390 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cell-Based Treatments: Advanced Therapies and Transplants. Transplant Proc. 2011 January - February;43(1):338-340 Authors: Botta R, Migliaccio G The introduction of Regulation 1394/2007/EC managing the use of tissue engineering products for the purpose of repairing, regenerating, or replacing missing tissue and cells has created a gray area where transplant and medicinal products overlap. The classification of such borderline products depends on the European Medicines Agency at the moment of marketing application. However, when these products first enter into the clinical development, the burden of definition falls on National competent authorities. The concept of "minimal manipulation" and of "heterologous use" are introduced to describe currently used criteria. PMID: 21335218 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Streamlining the generation of an osteogenic graft by 3D culture of unprocessed bone marrow on ceramic scaffolds. J Tissue Eng Regen Med. 2011 Feb 21; Authors: Chatterjea A, Renard AJ, Jolink C, van Blitterswijk CA, Boer JD Mesenchymal stromal cells are present in very low numbers in the bone marrow, necessitating their selective expansion on tissue culture plastic prior to their use in tissue-engineering applications. MSC expansion is laborious, time consuming, unphysiological and not economical, thus calling for automated bioreactor-based strategies. We and others have shown that osteogenic grafts can be cultured in bioreactors by seeding either 2D-expanded cells or by direct seeding of the mononuclear fraction of bone marrow. To further streamline this protocol, we assessed in this study the possibility of seeding the cells onto porous calcium phosphate ceramics directly from unprocessed bone marrow. Using predetermined volumes of bone marrow from multiple human donors with different nucleated cell counts, we were able to grow a confluent cell sheath on the scaffold surface in 3 weeks. Cells of stromal, endothelial and haematopoietic origin were detected, in contrast to grafts grown from 2D expanded cells, where only stromal cells could be seen. Upon implantation in nude mice, similar quantities of bone tissue were generated as compared to that obtained by using the conventional number of culture expanded cells from the same donor. We conclude that human osteogenic grafts can be efficiently prepared by direct seeding of cells from unprocessed bone marrow. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21337706 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Application of decellularized scaffold combined with loaded nanoparticles for heart valve tissue engineering in vitro. J Huazhong Univ Sci Technolog Med Sci. 2011 Feb;31(1):88-93 Authors: Deng C, Dong N, Shi J, Chen S, Xu L, Shi F, Hu X, Zhang X The purpose of this study was to fabricate decelluarized valve scaffold modified with polyethylene glycol nanoparticles loaded with transforming growth factor-β1 (TGF-β1), by which to improve the extracellular matrix microenvironment for heart valve tissue engineering in vitro. Polyethylene glycol nanoparticles were obtained by an emulsion-crosslinking method, and their morphology was observed under a scanning electron microscope. Decelluarized valve scaffolds, prepared by using trypsinase and TritonX-100, were modified with nanoparticles by carbodiimide, and then TGF-β1 was loaded into them by adsorption. The TGF-β1 delivery of the fabricated scaffold was measured by asing enzyme-linked immunosorbent assay. Whether unseeded or reseeded with myofibroblast from rats, the morphologic, biochemical and biomechanical characteristics of hybrid scaffolds were tested and compared with decelluarized scaffolds under the same conditions. The enzyme-linked immunosorbent assay revealed a typical delivery of nanoparticles. The morphologic observations and biological data analysis indicated that fabricated scaffolds possessed advantageous biocompatibility and biomechanical property beyond decelluarized scaffolds. Altogether this study proved that it was feasible to fabricate the hybrid scaffold and effective to improve extracellular matrix microenvironment, which is beneficial for an application in heart valve tissue engineering. PMID: 21336730 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Structural and biological evaluation of a multifunctional SWCNT-AgNPs-DNA/PVA bio-nanofilm. Anal Bioanal Chem. 2011 Feb 19; Authors: Subbiah RP, Lee H, Veerapandian M, Sadhasivam S, Seo SW, Yun K A bio-nanofilm consisting of a tetrad nanomaterial (nanotubes, nanoparticles, DNA, polymer) was fabricated utilizing in situ reduction and noncovalent interactions and it displayed effective antibacterial activity and biocompatibility. This bio-nanofilm was composed of homogenous silver nanoparticles (AgNPs) coated on single-walled carbon nanotubes (SWCNTs), which were later hybridized with DNA and stabilized in poly(vinyl alcohol) (PVA) in the presence of a surfactant with the aid of ultrasonication. Electron microscopy and bio-AFM (atomic force microscopy) images were used to assess the morphology of the nanocomposite (NC) structure. Functionalization and fabrication were examined using FT-Raman spectroscopy by analyzing the functional changes in the bio-nanofilm before and after fabrication. UV-visible spectroscopy and X-ray powder diffraction (XRD) confirmed that AgNPs were present in the final NC on the basis of its surface plasmon resonance (370 nm) and crystal planes. Thermal gravimetric analysis was used to measure the percentage weight loss of SWCNT (17.5%) and final SWCNT-AgNPs-DNA/PVA (47.7%). The antimicrobial efficiency of the bio-nanofilm was evaluated against major pathogenic organisms. Bactericidal ratios, zone of inhibition, and minimum inhibitory concentration were examined against gram positive and gram negative bacteria. A preliminary cytotoxicity analysis was conducted using A549 lung cancer cells and IMR-90 fibroblast cells. Confocal laser microscopy, bio-AFM, and field emission scanning electron microscopy (FE-SEM) images demonstrated that the NCs were successfully taken up by the cells. These combined results indicate that this bio-nanofilm was biocompatible and displayed antimicrobial activity. Thus, this novel bio-nanofilm holds great promise for use as a multifunctional tool in burn therapy, tissue engineering, and other biomedical applications. PMID: 21336791 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Physiologically based mathematical model of transduction of mechanobiological signals by osteocytes. Biomech Model Mechanobiol. 2011 Feb 20; Authors: Hambli R, Rieger R Developing mathematical models describing the bone transduction mechanisms, including mechanical and metabolic regulations, has a clear practical applications in bone tissue engineering. The current study attempts to develop a plausible physiologically based mathematical model to describe the mechanotransduction in bone by an osteocyte mediated by the calcium-parathyroid hormone regulation and incorporating the nitric oxide (NO) and prostaglandin E2 (PGE2) effects in early responses to mechanical stimulation. The inputs are mechanical stress and calcium concentration, and the output is a stimulus function corresponding to the stimulatory signal to osteoblasts. The focus will be on the development of the mechanotransduction model rather than investigating the bone remodeling process that is beyond the scope of this study. The different components of the model were based on both experimental and theoretical previously published results describing some observed physiological events in bone mechanotransduction. Current model is a dynamical system expressing the mechanotransduction response of a given osteocyte with zero explicit space dimensions, but with a dependent variable that records signal amplitude as a function of mechanical stress, some metabolic factors release, and time. We then investigated the model response in term of stimulus signal variation versus the model inputs. Despite the limitations of the model, predicted and experimental results from literature have the same trends. PMID: 21336969 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A computational tool for the upscaling of regular scaffolds during in vitro perfusion culture. Tissue Eng Part C Methods. 2011 Feb 18; Authors: Truscello S, Schrooten J, Van Oosterwyck H Inhomogeneous and uncontrolled cellular and tissue responses in bone tissue engineering (TE) constructs, as a result of heterogeneous oxygen delivery throughout the scaffold volume, is one of the hurdles hampering clinical transfer of cell-scaffold combinations. This study presents an accurate and computationally efficient one-dimensional (1D) model that predicts the oxygen distribution for a regular cell-seeded scaffold in a perfusion bioreactor and the maximum (i.e. critical) scaffold length (Lmax) as a function of given oxygen constraints. After validation against Computational Fluid Dynamics (CFD) models, the 1D model was applied to calculate Lmax in the perfusion direction, to ensure appropriate oxygen levels throughout the TE construct during in vitro culture. Both cell-related (cell density and oxygen consumption rate) and bioreactor-related (oxygen constraints, flow rate) culture parameters were varied. Results demonstrated the substantial influence of the culture parameters on Lmax. In conclusion, the presented computational tool was able to predict oxygen distribution and maximum scaffold length for regular cell-seeded scaffold. It can be used to design perfusion experiments where quantitative knowledge on both oxygen and flow characteristics is needed. PMID: 21332298 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Sequential assembly of cell-laden hydrogel constructs to engineer vascular-like microchannels. Biotechnol Bioeng. 2011 Feb 17; Authors: Du Y, Ghodousi M, Qi H, Haas N, Xiao W, Khademhosseini A Microscale technologies, such as microfluidic systems, provide powerful tools for building biomimetic vascular-like structures for tissue engineering or in vitro tissue models. Recently, modular approaches have emerged as attractive approaches in tissue engineering to achieve precisely controlled architectures by using microengineered components. Here, we sequentially assembled microengineered hydrogels (microgels) into hydrogel constructs with an embedded network of microchannels. Arrays of microgels with predefined internal microchannels were fabricated by photolithography and assembled into 3D tubular construct with multi-level interconnected lumens. In the current setting, the sequential assembly of microgels occurred in a biphasic reactor and was initiated by swiping a needle to generate physical forces and fluidic shear. We optimized the conditions for assembly and successfully perfused fluids through the interconnected constructs. The sequential assembly process does not significantly influence cell viability within the microgels indicating its promise as a biofabrication method. Finally, in an attempt to build a biomimetic 3D vasculature, we incorporated endothelial cells and smooth muscle cells into an assembled construct with a concentric microgel design. The sequential assembly is simple, rapid, cost-effective and could be used for fabricating tissue constructs with biomimetic vasculature and other complex architectures. Biotechnol. Bioeng. © 2011 Wiley Periodicals, Inc. PMID: 21337336 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Improvement of HepG2/C3a cell functions in a microfluidic biochip. Biotechnol Bioeng. 2011 Feb 17; Authors: Prot JM, Aninat C, Griscom L, Razan F, Brochot C, Guillouzo CG, Legallais C, Corlu A, Leclerc E Current developments in tissue engineering and microtechnology fields allow the use of microfluidic biochip as microtools for in vitro investigations. In the present study, we describe the behaviour of HepG2/C3a cells cultivated in a poly (dimethylsiloxane) (PDMS) microfluidic biochip coupled to a perfusion system. Cell culture in the microfluidic biochip for 96h including 72h of perfusion provoked a 24h delay in cell growth compared to plate cultures. Inside the microfluidic biochip, few apoptosis and necrosis were detected along the culture and 3D cell organization was observed. Regarding the hepatic metabolism, glucose and glutamine consumptions as well as albumin synthesis were maintained. A transcriptomic analysis performed at 96h of culture using Affymetrix GeneChip demonstrated that 1025 genes with a fold change above 1.8 were statistically differentially expressed in the microfluidic biochip cultures compared to plate cultures. Among those genes, phase I enzymes involved in the xenobiotic's metabolism such as the cytochromes P450 (CYP) 1A1/2, 2B6, 3A4, 3A5 and 3A7 were up-regulated. The CYP1A1/2 up-regulation was associated with the appearance of CYP1A1/2's activity evidenced by using EROD biotransformation assay. Several phase II enzymes such as sulfotransferases (SULT1A1 and SULT1A2), UDP-glucuronyltransferase (UGT1A1, UGT2B7) and phase III transporters (such as MDR1, MRP2) were also up-regulated. In conclusion, microfluidic biochip could and provide an important insight to exploring the xenobiotic's metabolism. Altogether, these results suggest that this kind of biochip could be considered as a new pertinent tool for predicting cell toxicity and clearance of xenobiotics in vitro. Biotechnol. Bioeng. © 2011 Wiley Periodicals, Inc. PMID: 21337338 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effect of carbon nanotube coating of aligned nanofibrous polymer scaffolds on the neurite outgrowth of PC-12 cells. Cell Biol Int. 2011 Feb 21; Authors: Jin GZ, Kim M, Shin US, Kim HW Neurite outgrowth from endogenous or transplanted cells is important for neural regeneration following nerve tissue injury. Modified substrates often provide better environments for cell adhesion and neurite outgrowth. This study was conducted to determine if multi-walled carbon nanotubes (MWCNTs)-coated electrospun poly (L-lactic acid-co-3-caprolactone) (PLCL) nanofibers improved the neurite outgrowth of PC-12 cells. To accomplish this, two groups, PC-12 cells in either uncoated PLCL scaffolds or MWCNTs-coated PLCL scaffolds, were cultured for nine days. MWCNTs-coated PLCL scaffolds showed improved adhesion, proliferation and neurite outgrowth of PC-12 cells. These findings suggest that MWCNTs-coated nanofibrous scaffolds may be an attractive platform for cell transplantation application in neural tissue engineering. PMID: 21332449 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Poly(e-caprolactone) reinforced with sol-gel synthesized organic-inorganic hybrid fillers as composite substrates for tissue engineering. J Appl Biomater Biomech. 2010 Dec 21;8(3):146-152 Authors: Russo T, Gloria A, D'Antò V, D'Amora U, Ametrano G, Bollino F, De Santis R, Ausanio G, Catauro M, Rengo S, Ambrosio L Purpose: The importance of polymer-based composite materials to make multifunctional substrates for tissue engineering and the strategies to improve their performances have been stressed in the literature. Bioactive features of sol-gel synthesized poly(e-caprolactone)/TiO2 or poly(e-caprolactone)/ZrO2 organic-inorganic hybrid materials are widely documented. Accordingly, the aim of this preliminary research was to develop advanced composite substrates consisting of a poly(e-caprolactone) matrix reinforced with sol-gel synthesized PCL/TiO2 or PCL/ZrO2 hybrid fillers. ?Methods: Micro-computed tomography and atomic force microscopy analyses allowed to study surface topography and roughness. On the other hand, mechanical and biological performances were evaluated by small punch tests and Alamar BlueTM assay, respectively.?Results: Micro-computed tomography and atomic force microscopy analyses highlighted the effect of the preparation technique. Results from small punch tests and Alamar BlueTM assay evidenced that PCL reinforced with Ti2 (PCL=12, TiO2=88 wt%) and Zr2 (PCL=12, ZrO2=88 wt%) hybrid fillers provided better mechanical and biological performances.?Conclusions: PCL reinforced with Ti2 (PCL=12, TiO2=88 wt%) and Zr2 (PCL=12, ZrO2=88 wt%) hybrid fillers could be considered as advanced composite substrates for hard tissue engineering. PMID: 21337305 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mechanical stimulation to stimulate formation of a physiological collagen architecture in tissue-engineered cartilage: a numerical study. Comput Methods Biomech Biomed Engin. 2011 Feb;14(2):135-44 Authors: Khoshgoftar M, van Donkelaar CC, Ito K The load-bearing capacity of today's tissue-engineered (TE) cartilage is insufficient. The arcade-like collagen network in native cartilage plays an important role in its load-bearing properties. Inducing the formation of such collagen architecture in engineered cartilage can, therefore, enhance mechanical properties of TE cartilage. Considering the well-defined relationship between tensile strains and collagen alignment in the literature, we assume that cues for inducing this orientation should come from mechanical loading. In this study, strain fields prescribed by loading conditions of unconfined compression, sliding indentation and a novel loading regime of compression-sliding indentation are numerically evaluated to assess the probability that these would trigger a physiological collagen architecture. Results suggest that sliding indentation is likely to stimulate the formation of an appropriate superficial zone with parallel fibres. Adding lateral compression may stimulate the formation of a deep zone with perpendicularly aligned fibres. These insights may be used to improve loading conditions for cartilage tissue engineering. PMID: 21337221 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Wound healing and regenerative strategies. Oral Dis. 2011 Jan 7; Authors: Nauta A, Gurtner G, Longaker M Oral Diseases (2011) doi: 10.1111/j.1601-0825.2011.01787.x Wound healing is a complex biological process that affects multiple tissue types. Wounds in the oral cavity are particularly challenging given the variety of tissue types that exist in close proximity to one another. The goal of regenerative medicine is to facilitate the rapid replacement of lost or damaged tissue with tissue that is functional, and physiologically similar to what previously existed. This review provides a general overview of wound healing and regenerative medicine, focusing specifically on how recent advances in the fields of stem cell biology, tissue engineering, and oral disease could translate into improved clinical outcomes. PMID: 21332599 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | In vitro Cell Performances on Hydroxyapatite Particles/Poly(L-Lactic Acid) Nanofibrous Scaffolds with an Excellent Particle-along-Nanofiber Orientation. Acta Biomater. 2011 Feb 16; Authors: Peng F, Yu X, Wei M Highly porous hydroxyapatite (HA)/poly(L-lactide) (PLLA) nanofibrous scaffolds were prepared by incorporating needle-shaped nano- or micro-sized HA particles into PLLA nanofibers using electrospinning. The scaffolds had random or aligned fibrous assemblies and both types of HA particles were perfectly oriented along the fiber long axes. The biocompatibility and cell signaling property of these scaffolds were evaluated by an in vitro culture of rat osteosarcoma ROS17/2.8 cells on the scaffold surface. Cell morphology, viability and alkaline phosphatase (ALP) activity on each scaffold were examined at different time points. The HA/PLLA scaffolds exhibited higher cell viability and ALP activity than the pure PLLA scaffold. In addition, micro-sized HA particles supported cell proliferation and differentiation better than the nano-sized ones in random scaffolds through a 10-day culture period and in aligned scaffold at an early culture stage. And the fibrous assembly of the scaffold showed pronounced impact on the morphology of the cells in direct contact with the scaffold surface, but not on the cell proliferation and differentiation. Thus, HA/PLLA nanofibrous scaffolds can be good candidates for bone tissue engineering. PMID: 21333762 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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