|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | We are once again hoisting sail to move farther south (actually east and south) towards Panama. That means a hiatus in fresh items on the California Stem Cell Report at least until we find another Internet connection. How long will the break be? That is unknown but probably not more than three weeks. Less if we find an Internet cafe in one of the villages along the coast of Costa Rica or Panama. | | | | | | | | | | | | | | | | | | | | | | | | It is fair to say that the $3 billion California stem cell agency is not a spendthrift organization – at least as far as its operational budget goes.
That's the money for salaries of its 48 employees, outside contracts (the second biggest item in the budget), monitoring grant performance and so forth. The agency is limited by law to spending only six percent of its $3 billion for overhead, an | | | | | | | | | |  | |  | |  |
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