|  |  |  | | | | | TERMSC | | | | | | | | | | | | | | | | | | | Platelet Activation in Ovines Undergoing Sham Surgery or Implant of the Second Generation PediaFlow Pediatric Ventricular Assist Device. Artif Organs. 2011 Apr 5; Authors: Johnson Jr CA, Wearden PD, Kocyildirim E, Maul TM, Woolley JR, Ye SH, Strickler EM, Borovetz HS, Wagner WR The PediaFlow pediatric ventricular assist device (VAD) is a magnetically levitated turbodynamic pump under development for circulatory support of small children with a targeted flow rate range of 0.3-1.5 L/min. As the design of this device is refined, ensuring high levels of blood biocompatibility is essential. In this study, we characterized platelet activation during the implantation and operation of a second generation prototype of the PediaFlow VAD (PF2) and also performed a series of surgical sham studies to examine purely surgical effects on platelet activation. In addition, a newly available monoclonal antibody was characterized and shown to be capable of quantifying ovine platelet activation. The PF2 was implanted in three chronic ovine experiments of 17, 30, and 70 days, while surgical sham procedures were performed in five ovines with 30-day monitoring. Blood biocompatibility in terms of circulating activated platelets was measured by flow cytometric assays with and without exogenous agonist stimulation. Platelet activation following sham surgery returned to baseline in approximately 2 weeks. Platelets in PF2-implanted ovines returned to baseline activation levels in all three animals and showed an ability to respond to agonist stimulation. Late-term platelet activation was observed in one animal corresponding with unexpected pump stoppages related to a manufacturing defect in the percutaneous cable. The results demonstrated encouraging platelet biocompatibility for the PF2 in that basal platelet activation was achieved early in the pump implant period. Furthermore, this first characterization of the effect of a major cardiothoracic procedure on temporal ovine platelet activation provides comparative data for future cardiovascular device evaluation in the ovine model. PMID: 21463346 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | PDGFR{alpha}-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia. Proc Natl Acad Sci U S A. 2011 Apr 4; Authors: Tamai K, Yamazaki T, Chino T, Ishii M, Otsuru S, Kikuchi Y, Iinuma S, Saga K, Nimura K, Shimbo T, Umegaki N, Katayama I, Miyazaki JI, Takeda J, McGrath JA, Uitto J, Kaneda Y The role of bone marrow cells in repairing ectodermal tissue, such as skin epidermis, is not clear. To explore this process further, this study examined a particular form of cutaneous repair, skin grafting. Grafting of full thickness wild-type mouse skin onto mice that had received a green fluorescent protein-bone marrow transplant after whole body irradiation led to an abundance of bone marrow-derived epithelial cells in follicular and interfollicular epidermis that persisted for at least 5 mo. The source of the epithelial progenitors was the nonhematopoietic, platelet-derived growth factor receptor α-positive (Lin(-)/PDGFRα(+)) bone marrow cell population. Skin grafts release high mobility group box 1 (HMGB1) in vitro and in vivo, which can mobilize the Lin(-)/PDGFRα(+) cells from bone marrow to target the engrafted skin. These data provide unique insight into how skin grafts facilitate tissue repair and identify strategies germane to regenerative medicine for skin and, perhaps, other ectodermal defects or diseases. PMID: 21464317 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Intraocular Transplantation of Human Adipose-Derived Mesenchymal Stem Cells in a Rabbit Model of Experimental Retinal Holes. Ophthalmic Res. 2011 Apr 5;46(4):199-207 Authors: Xuqian W, Kanghua L, Weihong Y, Xi Y, Rongping D, Qin H, Fangtian D, Chunhua Zhao R Aims: To investigate whether human adipose-derived mesenchymal stem cell (hAD-MSC) transplantation would ameliorate the healing process of a rabbit model of retinal holes. Methods: Retinal holes were made in the left eyes of 20 New Zealand white rabbits and randomly filled by hAD-MSCs (transplantation group) or phosphate-buffered saline (control group), respectively. Frequency-domain optical coherence tomography (OCT) scan was performed on days 2, 4, 12, 20 and 32 postoperatively, and immunofluorescence was performed on days 12 and 32 to further identify the cell types of the injured area. Results: Frequency-domain OCT scan showed that the mean center thickness of the reconstructed tissue reached a normal level on day 12 in the transplantation group, while in the control group, the mean center thickness was normal on day 32. Furthermore, compared to the control group where only anti-glial fibrillary acidic protein-labeled glial-like cells were detected, donor-derived opsin-positive photoreceptor-like cells and protein kinase C-positive bipolar-like cells were sporadically found in the transplantation group. Conclusions: Transplanted hAD-MSCs could engraft in the retinal hole of a rabbit model, and clearly accelerated the healing process and ameliorated injury recovery. PMID: 21464577 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Biomedical and social contributions to sustainability. Philos Transact A Math Phys Eng Sci. 2011 May 13;369(1942):1730-47 Authors: Wilmut I, Wongtawan T, Quigley M, Sullivan G Over the past two or three centuries, biomedical advances have provided methods to prevent and treat infectious diseases. These changes have greatly reduced human suffering and enhanced sustainability by allowing people to live longer and healthier lives. The challenge for the coming centuries will be to ensure that these longer, healthier lives are also more productive lives. We must build on the gains of the past by translating new discoveries in regenerative medicine into therapies for degenerative and genetic diseases. Stem cells may be used to identify drugs that prevent the development of symptoms or to replace cells that have either died or lost their physiological function. In the case of genetic diseases, it may be possible to correct the genetic error. While most conditions that might be treated in these ways are common to all communities, some are more prevalent in specific races. Provision of these and other benefits depends not only on attainment of the research objectives, but also upon our ability to make treatment opportunities available throughout both developed and developing communities. The long history of researching and treating infectious diseases shows that it may take many decades to reap the full benefit of the new biological understanding. PMID: 21464068 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Comparably accelerated vascularization by preincorporation of aortic fragments and mesenchymal stem cells in implanted tissue engineering constructs. J Biomed Mater Res A. 2011 Apr 4; Authors: Schumann P, von See C, Kampmann A, Lindhorst D, Tavassol F, Kokemüller H, Bormann KH, Gellrich NC, Rücker M The demanding need for tissue replacement resulted in manifold approaches for the construction of different tissues. One common problem which hampers the clinical usage of tissue engineering constructs is a limited vascularization. In an attempt to accelerate the vascularization of tissue engineering constructs we compared the usage of bone marrow mesenchymal stem cells (bmMSCs) and fragments derived from the aorta in vivo. Tissue engineering constructs composed of PLGA scaffolds containing Matrigel (n = 8), aortic fragments embedded in Matrigel (n = 8), bmMSCs embedded in Matrigel (n = 8), and aortic fragments embedded in Matrigel combined with bmMSCs (n = 8) were implanted into dorsal skinfold chambers of balb/c mice and analyzed repetitively over 14 days. In all groups a weak inflammatory response was transiently apparent. Vascularization was significantly (p = 0.05) accelerated in bmMSC and aortic fragments containing constructs compared with Matrigel alone, demonstrated by a distinctly increased microvascular density throughout the whole experiment. The combination of bmMSCs and aortic fragments showed no additional effect compared with bmMSCs and aortic fragments alone. The accelerated vascularization and microvascular density of tissue engineering constructs triggered by bmMSCs and aortic fragments is comparable. Thus aortic fragments provide a new promising source for clinical relevant tissue engineering constructs. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011. PMID: 21465643 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Fabrication of fibrinogen/P(LLA-CL) hybrid nanofibrous scaffold for potential soft tissue engineering applications. J Biomed Mater Res A. 2011 Apr 4; Authors: He C, Xu X, Zhang F, Cao L, Feng W, Wang H, Mo X Coelectrospinning of native proteins and elastic synthetic polymers is an attractive technique to fabricate hybrid fibrous scaffolds that combine the bioactivity and mechanical features of each material component. In this study, hybrid fibrous scaffolds composed of synthetic P(LLA-CL) elastomeric and naturally derived fibrinogen protein were fabricated and characterized for their bioactive and physiochemical properties. Fiber diameters of hybrid scaffolds increased with increasing P(LLA-CL) content, and the shape of fibers changed from cylindrical shape on pure polymer scaffolds to flat structure on hybrid scaffolds. Characterizations of ATR-FTIR, XRD, and thermal properties indicated that the hybrid scaffolds contain two different phases, one composed of pure fibrinogen and the other corresponding to a mixture of fibrinogen and P(LLA-CL), and no obvious chemical reaction takes place between two components. The hybrid fibrous scaffolds showed tailorable degradation rates than pure P(LLA-CL) and higher mechanical properties than pure fibrinogen, and both tensile strength and breaking strain increased with increasing P(LLA-CL) content. In Vitro studies revealed that L929 cells on hybrid scaffolds achieved relatively higher level of cell attachment after 12 h of culture and significant increased cell proliferation rate after 7 days of culture, when compared with pure fibrinogen and P(LLA-CL) scaffolds, and the cells exhibited a spreading polygonal shape on the hybrid fibrous surfaces compared to a round shape on surfaces of pure polymer scaffolds. Therefore, the fibrinogen/P(LLA-CL) hybrid fibrous scaffolds possess the combined benefits of each individual component, which make it capable as scaffolds for soft tissue reconstruction. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011. PMID: 21465642 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Tissue-engineered fascia from vaginal fibroblasts for patients needing reconstructive pelvic surgery. Int Urogynecol J Pelvic Floor Dysfunct. 2010 Sep;21(9):1085-93 Authors: Hung MJ, Wen MC, Hung CN, Ho ES, Chen GD, Yang VC Mesh-augmented reconstructive surgery for pelvic organ prolapse (POP) does not meet clinical expectations. A tissue-engineered fascia equivalent needs to be developed. PMID: 20480140 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Fetal adnexa derived stem cells from domestic animal: progress and perspectives. Theriogenology. 2011 May;75(8):1400-15 Authors: Cremonesi F, Corradetti B, Lange Consiglio A The fetal adnexa such as umbilical cord, amnion and amniotic fluid have been proposed as ideal sources of different stem cell lineages. Use of adnexal tissue has many potential advantages, including the noninvasive nature of the isolation procedure, the large tissue mass from which cells can be harvested with high efficiency and the potential of these cells to differentiate. Moreover, particularly in human medicine, the harvesting of these tissues is more ethically acceptable making these sources of stem cells very attractive for regenerative therapies and biotechnological applications. The adnexal tissue cells preserve some of the characteristics of the primitive embryonic layers from which they originate. Indeed, many studies indicate that these stem cells exhibit some features of embryonic stem cells as expression of embryonic markers and proliferation capability, without showing immunogenicity. However, the differentiation potential of these cells, either in vivo or in vitro, is intermediate between the pluripotent embryonic stem cells and the multipotent adult stem cells. Non-embryonic extra-fetal derived stem cells have opened new perspectives for developmental biology and for regenerative medicine, not only in humans but also in animals. In this update, we report the state of the art of fetal adnexa-derived stem cells from domestic animals and analyze their applications and potential uses in veterinary medicine. PMID: 21463720 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Functional characterization of human coronary artery smooth muscle cells under cyclic mechanical strain in a degradable polyurethane scaffold. Biomaterials. 2011 Apr 2; Authors: Sharifpoor S, Simmons CA, Labow RS, Paul Santerre J There are few synthetic elastomeric biomaterials that simultaneously provide the required biological conditioning and the ability to translate biomechanical stimuli to vascular smooth muscle cells (VSMCs). Biomechanical stresses are important physiological elements that regulate VSMC function, and polyurethane elastomers are a class of materials capable of facilitating the translation of stress induced biomechanics. In this study, human coronary artery smooth muscle cells (hCASMCs), which were seeded into a porous degradable polar/hydrophobic/ionic (D-PHI) polyurethane scaffold, were subjected to uniaxial cyclic mechanical strain (CMS) over a span of four weeks using a customized bioreactor. The distribution, proliferation and contractile protein expression of hCASMCs in the scaffold were then analyzed and compared to those grown under static conditions. Four weeks of CMS, applied to the elastomeric scaffold, resulted in statistically greater DNA mass, more cell area coverage and a better distribution of cells deeper within the scaffold construct. Furthermore, CMS samples demonstrated improved tensile mechanical properties following four weeks of culture, suggesting the generation of more extracellular matrix within the polyurethane constructs. The expression of smooth muscle α-actin, calponin and smooth muscle myosin heavy chain and the absence of Ki-67+ cells in both static and CMS cultures, throughout the 4 weeks, suggest that hCASMCs retained their contractile character on these biomaterials. The study highlights the importance of implementing physiologically-relevant biomechanical stimuli in the development of synthetic elastomeric tissue engineering scaffolds. PMID: 21463894 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Large animal models for cardiac stem cell therapies. Theriogenology. 2011 May;75(8):1416-25 Authors: Gandolfi F, Vanelli A, Pennarossa G, Rahaman M, Acocella F, Brevini TA Cardiovascular disease is the leading cause of death in developed countries and is one of the leading causes of disease burden in developing countries. Therapies have markedly increased survival in several categories of patients, nonetheless mortality still remains high. For this reason high hopes are associated with recent developments in stem cell biology and regenerative medicine that promise to replace damaged or lost cardiac muscle with healthy tissue, and thus to dramatically improve the quality of life and survival in patients with various cardiomyopathies. Much of our insight into the molecular and cellular basis of cardiovascular biology comes from small animal models, particularly mice. However, significant differences exist with regard to several cardiac characteristics when mice are compared with humans. For this reason, large animal models like dog, sheep and pig have a well established role in cardiac research. A distinct characteristic of cardiac stem cells is that they can either be endogenous or derive from outside the heart itself; they can originate as the natural course of their differentiation programme (e.g., embryonic stem cells) or can be the result of specific inductive conditions (e.g., mesenchymal stem cells). In this review we will summarize the current knowledge on the kind of heart-related stem cells currently available in large animal species and their relevance to human studies as pre-clinical models. PMID: 21463721 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Differential transformation capacity of Src family kinases during the initiation of prostate cancer. Proc Natl Acad Sci U S A. 2011 Apr 4; Authors: Cai H, Smith DA, Memarzadeh S, Lowell CA, Cooper JA, Witte ON Src family kinases (SFKs) are pleiotropic activators that are responsible for integrating signal transduction for multiple receptors that regulate cellular proliferation, invasion, and metastasis in a variety of human cancers. Independent groups have identified increased expression of individual SFK members during prostate cancer progression, raising the question of whether SFKs display functional equivalence. Here, we show that Src kinase, followed by Fyn kinase and then Lyn kinase, exhibit ranked tumorigenic potential during both paracrine-induced and cell-autonomous-initiated prostate cancer. This quantitative variation in transformation potential appears to be regulated in part by posttranslational palmitoylation. Our data indicate that development of inhibitors against specific SFK members could provide unique targeted therapeutic strategies. PMID: 21464326 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Reconstruction of the alveolar cleft: can growth factor-aided tissue engineering replace autologous bone grafting? A literature review and systematic review of results obtained with bone morphogenetic protein-2. Clin Oral Investig. 2011 Apr 5; Authors: van Hout WM, Mink van der Molen AB, Breugem CC, Koole R, Van Cann EM The alveolar cleft in patients with clefts of lip, alveolus and palate (CLAP) is usually reconstructed with an autologous bone graft. Harvesting of autologous bone grafts is associated with more or less donor site morbidity. Donor site morbidity could be eliminated if bone is fabricated by growth factor-aided tissue engineering. The objective of this review was to provide an oversight on the current state of the art in growth factor-aided tissue engineering with regard to reconstruction of the alveolar cleft in CLAP. Medline, Embase and Central databases were searched for articles on bone morphogenetic protein 2 (BMP-2), bone morphogenetic protein 7, transforming growth factor beta, platelet-derived growth factor, insulin-like growth factor, fibroblast growth factor, vascular endothelial growth factor and platelet-rich plasma for the reconstruction of the alveolar cleft in CLAP. Two-hundred ninety-one unique search results were found. Three articles met our selection criteria. These three selected articles compared BMP-2-aided bone tissue engineering with iliac crest bone grafting by clinical and radiographic examinations. Bone quantity appeared comparable between the two methods in patients treated during the stage of mixed dentition, whereas bone quantity appeared superior in the BMP-2 group in skeletally mature patients. Favourable results with BMP-2-aided bone tissue engineering have been reported for the reconstruction of the alveolar cleft in CLAP. More studies are necessary to assess the quality of bone. Advantages are shortening of the operation time, absence of donor site morbidity, shorter hospital stay and reduction of overall cost. PMID: 21465220 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stem Cell Therapy in Stroke: Designing Clinical Trials. Neurochem Int. 2011 Mar 28; Authors: Kalladka D, Muir KW Stroke is a common and disabling condition that represents a potentially attractive target for regenerative therapy. Stem cells from a wide range of origins have been investigated in studies using animal models of stroke, with evidence that neural or mesenchymal cells migrate to the site of ischemic injury after intravascular or intraparenchymal delivery, and that a proportion of cells survive and differentiate into cells with characteristics of neurons or glia. In some studies there is evidence of electrical function of transplanted cells. Some studies report improvements in neurological function with cell implantation even when undertaken up to 30 days after the stroke is induced. Few clinical trials have been undertaken to date, with two studies of a teratocarcinoma-derived cell line delivered by direct brain injection, and two of bone-marrow derived mesenchymal stem cells delivered intravascularly. Ongoing trials of other cell lines are exploring safety. There are considerable difficulties in designing future efficacy trials, some being generic to the field of regenerative treatment in stroke, and some that are specific to stem cells or their mode of delivery. PMID: 21453739 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Three-dimensional glass-derived scaffolds for bone tissue engineering: Current trends and forecasts for the future. J Biomed Mater Res A. 2011 Apr 4; Authors: Baino F, Vitale-Brovarone C Biomaterials used in regenerative medicine are often designed to act as 3D porous templates (scaffolds) able to support and promote the growth and repair of natural tissues. Some types of glasses have a great potential for making bone tissue engineering scaffolds, as they can bond to host bone, stimulate bone cells toward osteogenesis, and resorb at the same time as the bone is repaired. This review article highlights the evolution of glass-based scaffolds for bone tissue engineering; specifically, the features, limitations, and advantages of the different types of glass-derived scaffolds proposed in the literature (macroporous glass-ceramic, sol-gel glass, composite, graded, hybrid, and hierarchical implants) are critically examined, discussed, and compared. Future directions for the research are also suggested, highlighting the promise of multifunctional systems able to combine bone regeneration and drug release abilities, the increasing role of nondestructive advanced imaging techniques, such as X-ray microtomography, for scaffolds investigation and the potential of stem cells incorporation into scaffolds. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011. PMID: 21465645 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Treatment and risk factor analysis of hypoglycemia in diabetic rhesus monkeys. Exp Biol Med (Maywood). 2011 Feb;236(2):212-8 Authors: He S, Chen Y, Wei L, Jin X, Zeng L, Ren Y, Zhang J, Wang L, Li H, Lu Y, Cheng J In order to anticipate and promptly treat hypoglycemia in diabetic monkeys treated with insulin or other glucose-lowering drugs, the relationships between the incidence and symptoms of hypoglycemia in these animals, and many factors involved in model development and sustainment were analyzed. Different procedures were performed on 22 monkeys for the induction of diabetes. The monkey models were evaluated by blood glucose, insulin, C-peptide levels and intravenous glucose tolerance tests. A glucose treatment program for the diabetic monkeys was administered and laboratory tests were regularly performed. A standard procedure of hypoglycemia treatment was established and the risk factors of hypoglycemia were analyzed by a logistic regression model. Furthermore, the relationships between the four methods of diabetes induction, renal function, glycemic control and hypoglycemia were studied using one-way analysis of variance and t-test. We found that the hypoglycemic conditions of diabetic monkeys were improved rapidly by our treatment. The statistical analysis suggested that the modeling methods, renal function and glycemic control were related to the incidence of hypoglycemia. In detail, the progress of diabetes, effects of glycemic control and, particularly, the severity of the hypoglycemia differed according to the induction strategy used. The models induced by partial pancreatectomy with low-dose streptozotocin were not prone to hypoglycemia and their glycemic controls were stable. However, the models induced by total pancreatectomy were more vulnerable to severe hypoglycemia and their glycemic controls were the most unstable. Moreover, the levels of blood creatinine and triglyceride increased after the development of diabetes, which was related to the occurrence of hypoglycemia. In conclusion, we suggested that total pancreatectomy and renal impairment are two important risk factors for hypoglycemia in diabetic monkeys. More attention should be paid to daily care of diabetic monkeys, particularly monitoring and protecting their renal function. PMID: 21321318 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Real-time label-free monitoring of adipose-derived stem cell differentiation with electric cell-substrate impedance sensing. Proc Natl Acad Sci U S A. 2011 Apr 4; Authors: Bagnaninchi PO, Drummond N Real-time monitoring of stem cells (SCs) differentiation will be critical to scale-up SC technologies, while label-free techniques will be desirable to quality-control SCs without precluding their therapeutic potential. We cultured adipose-derived stem cells (ADSCs) on top of multielectrode arrays and measured variations in the complex impedance Z* throughout induction of ADSCs toward osteoblasts and adipocytes. Z* was measured up to 17 d, every 180 s, over a 62.5-64kHz frequency range with an ECIS Z instrument. We found that osteogenesis and adipogenesis were characterized by distinct Z* time-courses. Significant differences were found (P = 0.007) as soon as 12 h post induction. An increase in the barrier resistance (Rb) up to 1.7 ohm·cm(2) was associated with early osteo-induction, whereas Rb peaked at 0.63 ohm·cm(2) for adipo-induced cells before falling to zero at t = 129 h. Dissimilarities in Z* throughout early induction (<24 h) were essentially attributed to variations in the cell-substrate parameter α. Four days after induction, cell membrane capacitance (Cm) of osteo-induced cells (Cm = 1.72 ± 0.10 μF/cm(2)) was significantly different from that of adipo-induced cells (Cm = 2.25 ± 0.27 μF/cm(2)), indicating that Cm could be used as an early marker of differentiation. Finally, we demonstrated long-term monitoring and measured a shift in the complex plane in the middle frequency range (1 kHz to 8 kHz) between early (t = 100 h) and late induction (t = 380 h). This study demonstrated that the osteoblast and adipocyte lineages have distinct dielectric properties and that such differences can be used to perform real-time label-free quantitative monitoring of adult stem cell differentiation with impedance sensing. PMID: 21464296 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effects of BMP-2 and vitamin D(3) on the osteogenic differentiation of adipose stem cells. Biochem Biophys Res Commun. 2011 Apr 1; Authors: Song I, Kim BS, Kim CS, Im GI We studied the effect of bone morphogenetic protein-2 (BMP-2) and vitamin D(3) on the osteogenic differentiation of adipose stem cells (ASCs). ASCs were treated with 10, 50, 100ng/ml of BMP-2, and 10(-8), 10(-7), 10(-6)M vitamin D(3.) Then, to investigate the effects of combined treatment, ASCs were treated with BMP-2 and vitamin D(3) dose-dependently and time-dependently. The osteogenic differentiation was assessed by alkaline phosphatase (ALP) activities/staining and the mineralization was evaluated by Alizarin red staining. ALP activity and mineralization dose-dependently increased in early stages (ALP on 7(th) day and mineralization on the 14(th) day) while all three doses of BMP-2 or vitamin D(3) showed comparable effects in late stages (ALP on the 14(th) day and mineralization on the 21(st) day) in ASCs. BMP-2 and vitamin D3 had synergistic effect on the osteogenic differentiation of ASCs. While all three doses of BMP-2 acted similarly in reinforcing the effect of vitamin D(3), vitamin D(3) dose-dependently augmented the osteogenic effect of BMP-2. When BMP-2 was constantly treated, vitamin D(3) effect did not differ depending on the period of vitamin D(3) treatment. However, when vitamin D3 was constantly treated, the BMP was more effective when treated for the last 7 days than when treated for the first 7 days. In conclusion, BMP-2 and vitamin D3 promote osteogenic differentiation of ASCs, and can work synergistically. These results can be used to induce effective and economical osteogenic induction of ASCs for bone tissue engineering. PMID: 21463608 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative Medicine , Ahead of Print, Pages 1-8.
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