|  |  |  | | | | | TERMSC | | | | | | | | | | | | | | | | | | | Characterization of bionanocomposite scaffolds comprised of amine-functionalized gold nanoparticles and silicon carbide nanowires crosslinked to an acellular porcine tendon. J Biomed Mater Res B Appl Biomater. 2011 Mar 10; Authors: Deeken CR, Fox DB, Bachman SL, Ramshaw BJ, Grant SA As one of the most common proteins found in the human body, collagen is regarded as biocompatible and has many properties making it ideal for soft-tissue repair applications. However, collagen matrices fabricated from purified forms of collagen are notoriously weak and easily degraded by the body. The extracellular matrix of many tissues including human dermis, porcine dermis, and porcine small intestine submucosa are often utilized instead, and several of these scaffolds are crosslinked. Crosslinking has been shown to improve the mechanical properties of collagenous tissues and increase their resistance to degradation. In this study we investigated two novel "bionanocomposite" materials in which either gold nanoparticles or silicon carbide nanowires were crosslinked to a porcine tendon. Scanning electron micrographs confirmed that the nanomaterials were successfully crosslinked to the tissues. A collagenase assay, tensile testing, flow cytometry, and bioreactor studies were also performed to further characterize the properties of these novel materials. The results of these studies indicated that crosslinking porcine diaphragm tissues with nanomaterials resulted in scaffolds with improved resistance to enzymatic degradation and appropriate biocompatibility characteristics, thus warranting further study of these materials for soft tissue repair and tissue engineering applications. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater , 2011. PMID: 21394904 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Embryonic stem cell extracts: use in differentiation and reprogramming. Regen Med. 2011 Mar;6(2):215-27 Authors: Han J, Sidhu K Stem cells have been studied extensively for decades and they have the inherent capacity to self-renew as well as to generate one or more types of specialized cells. The current focus of research on stem cells, particularly on embryonic stem cells, is on directed differentiation of these cells into specific cell types for future regenerative medicine. For the past few years, the process of reprogramming, which mediates convertion of somatic cells to their pluripotent state, has been given much attention, as it provides a possible source of autologous stem cells. In addition, understanding the molecular mechanism of differentiation and reprogramming has long been a subject of interest. In this article, we have briefly introduced stem cells and discussed the use of embryonic stem cells in reprogramming of somatic cells and differentiation to different lineages. The application of embryonic stem cells extracts in inducing reprogramming and transdifferentiation has also been described and discussed. Should this approach be successful, patient-specific cells will be produced safely and the likelihood of rejection will be decreased when used in cell therapy for many debilitating human diseases for which there is no cure such as Parkinson's disease, Alzheimer's disease, diabetes and others. PMID: 21391855 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Inhibition of Delta1 promotes differentiation of odontoblasts and inhibits proliferation of human dental pulp stem cell in vitro. Arch Oral Biol. 2011 Mar 8; Authors: Wang X, He F, Tan Y, Tian W, Qiu S OBJECTIVE: Dental pulp stem cells (DPSCs) have been receiving more attentions recently as an important biomaterial for tissue engineering. Notch signalling plays a key role in regulating self-renewal and differentiation of a variety of cells. The objective of this study is to investigate the effects of Notch-Delta1 RNA interference (RNAi) on the proliferation and differentiation of human dental pulp stem cells in vitro. DESIGN: In the present study, we performed gene knockdown of Notch ligand Delta1 in DPSCs using lentivirus-mediated Delta1-RNAi. Changes of proliferation in DPSCs/Delta1-RNAi were examined by cell cycle analysis, Cell viability assay (CCK-8) and Western blot analysis of proliferating cell nuclear antigen (PCNA). Cells were cultured in odontoblast differentiation-inducing medium, and the differentiation of cells was detected with Alkaline phosphatase ALP activity assay, Alizarin red S staining, calcium concentration measurement, and Western blot analysis of Dentine sialophosphoprotein (DSPP). RESULTS: Lentivirus-mediated Delta1-RNAi stably knocked-down the expression of Delta1 and Notch signalling, and some of DPSCs/Delta1-RNAi displayed changes in morphology or DSPP expression. The growth rate of Delta1-deficient DPSCs was significantly suppressed as compared with wild type DPSCs and control lentivirus vector transfected DPSCs. Furthermore, the differentiating capability of DPSCs/Delta1-RNAi into odontoblasts is much higher than the two control groups. CONCLUSIONS: Notch signalling plays a crucial role in regulating self-renewal and differentiation in DPSCs. The deficient Notch signalling inhibits the self-renewal capacity of DPSCs and tends to induce DPSCs differentiation under odontoblast differentiation-inducing conditions. These findings suggested that DPSCs/Delta1-RNAi might be applicable to stem cell therapies and tooth tissue engineering. PMID: 21392732 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Institutional Profile: The International Society for Cellular Therapy: evolving to meet the demands of the regenerative medicine industry. Regen Med. 2011 Mar;6(2):163-6 Authors: Maziarz RT, Arthurs J, Horwitz E The International Society for Cellular Therapy is a global association driving the translation of scientific research to deliver innovative cellular therapies to patients. Established in 1992, its membership and leadership comprises world-class scientists, clinicians, technologists, biotech/pharma and regulatory professionals from 40 countries focused on preclinical and translational aspects of developing cell therapy products. The International Society for Cellular Therapy has evolved in alignment with the maturation of the field of cell therapy and regenerative medicine to create forums for discussion of shared concerns for commercialization of cell therapies and of development of consensus standards, recognizing that true commercialization depends upon the translational scientific community, the regional regulatory and policy institutions, and the technology support and capital investment from industry. It exists to facilitate the international work of many, to spawn new initiatives, and to synergize with other stakeholders to create the best outcome for the many patients across the world depending on the answers and improved health that cellular therapeutics will provide them. PMID: 21391849 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerated teeth: the future of tooth replacement? Regen Med. 2011 Mar;6(2):135-9 Authors: Mitsiadis TA, Papagerakis P PMID: 21391845 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Cardiac tumorgenic potential of induced pluripotent stem cells in an immunocompetent host with myocardial infarction. Regen Med. 2011 Mar;6(2):171-8 Authors: Ahmed RP, Ashraf M, Buccini S, Shujia J, Haider HKh Aim: Genetic reprogramming of somatic cells with stemness genes to restore their pluripotent status is being studied extensively to generate pluripotent stem cells as an alternative to embryonic stem cells. This study was designed to examine the effectiveness of skeletal myoblast-derived induced pluripotent stem cells (SkiPS) from young male Oct4/GFP transgenic mice for regeneration of the infarcted heart. Methods & results: A mouse model of permanent coronary artery ligation was developed in young female immunocompetent C57BL/6J or C57BL/6x129S4 SV/jae Oct4/GFP mice. SkiPS labeled with Q-dots (3 × 10(5) in 10 µl basal Dulbecco's modified Eagle's medium) were transplanted in and around the area of infarct immediately after coronary artery ligation (n = 16) under direct vision. Control mice (n = 12) were injected with the same number of skeletal myoblasts. Histological studies documented successful engraftment of SkiPS in all the surviving animals 4 weeks later. However, six of the 16 SkiPS-transplanted (37.5%) animal hearts showed intramural teratomas, whereas no tumor growth was observed in the control mice. Q-dot-labeled donor cells were also observed at the site of tumors. Histological studies revealed that teratomas were composed of cells from all of the three embryonic germ layers. Ultra-structure studies confirmed the histological findings and showed regions with well-organized myofibrillar structures in the tumors. Conclusion: Undifferentiated induced pluripotent stem cells should not be recommended for cardiac transplantation unless screened for specific teratogenic precursors or predifferentiated into cardiac lineage prior to transplantation. PMID: 21391851 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Industry Update: Latest developments in stem cell research and regenerative medicine. Regen Med. 2011 Mar;6(2):145-56 Authors: Ilic D PMID: 21391847 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Hepatogenic engineering from human bone marrow mesenchymal stem cells in porous polylactic glycolic acid scaffolds under perfusion culture. J Tissue Eng Regen Med. 2011 Mar 10; Authors: Wang J, Zong C, Shi D, Wang W, Shen D, Liu L, Tong X, Zheng Q, Gao C Bone marrow mesenchymal stem cells (MSCs) are promising candidates for cell therapy and tissue engineering. We used mesenchymal stem cells from human bone marrow (hMSCs) as the seeding cells to investigate the potential of hepatocytic differentiation of hMSCs in porous polylactic glycolic acid (PLGA) scaffolds under perfusion induction. hMSCs were seeded and proliferated in PLGA scaffolds, and then induced into hepatocyte-like cells with hepatogenic medium in perfusion and static cultures. The results showed that hMSCs could be induced into hepatocyte-like cells in PLGA scaffolds with hepatogenic medium in both static and perfusion induction systems. However, perfusion induction was more effective for cellularity in PLGA scaffolds than in static induction. Cells in the scaffold induced by the hepatogenic medium expressed hepatocyte-specific genes cytokeratin 19 (CK19), α-fetoprotein (αFP), cytokeratin 18 (CK18), albumin and cytochrome P4503A4 (CYP3A4) in a time-dependent manner. Induced cells stained positive for αFP and albumin. Induced cells also acquired the functional characteristics of hepatocytes, i.e. secretion of urea and albumin. In a comparison of survival and hepatogenic differentiation of hMSCs between perfusion and static induction, perfusion induction increased the survival and the uniform distribution of induced cells in scaffolds, which resulted in a higher efficiency of hepatogenesis in the PLGA construct with hMSCs. The oscillatory perfusion induction system combined with the hepatogenic medium should be a valuable and convenient tool for in vitro hepatic tissue engineering using hMSCs. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21394930 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Chitosan nanoparticles as a dual growth factor delivery system for tissue engineering applications. Int J Pharm. 2011 Mar 7; Authors: Rajam M, Pulavendran S, Rose C, Mandal AB Growth factors are essential in cellular signaling for migration, proliferation, differentiation and maturation. Sustainable delivery of therapeutic as well as functional proteins is largely required in the pharmacological and regenerative medicine. Here we have prepared chitosan nanoparticles (CNP) and incorporated growth factors such as epidermal growth factor (EGF) and fibroblast growth factor (FGF), either individually or in combination, which could ultimately be impregnated into engineered tissue construct. CNP was characterized by fourier transform infrared spectroscopy (FTIR), Zeta sizer and high resolution transmission electron microscope (HRTEM). The particles were in the size range of 50-100nm with round and flat shape. The release kinetics of both EGF and FGF incorporated CNP showed the release of growth factors in a sustained manner. Growth factors incorporated nanoparticles did not show any toxicity against fibroblasts up to 4mg/ml culture medium. Increased proliferation of fibroblasts in vitro evidenced the delivery of growth factors from CNP for cellular signaling. Western blotting results also revealed the poor inflammatory response showing less expression of proinflammatory cytokines such as IL-6 and TNFα in the macrophage cell line J774 A-1. PMID: 21392563 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine. Opportunities and challenges: a brief overview. J R Soc Interface. 2010 Dec 6;7 Suppl 6:S777-81 Authors: Polak DJ Regenerative medicine is a new multi-disciplinary field aiming at the repair or replacement of disease body parts. The field is progressing at an unprecedented pace and although the opportunities are immense, many hurdles lie ahead. This brief review analyses the opportunities and challenges faced by regenerative medicine. PMID: 20826477 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Coordination of fingertip forces during precision grip in premanifest Huntington's disease. Mov Disord. 2011 Mar 10; Authors: Rao AK, Gordon AM, Marder KS Precision grip control is important for accurate object manipulation and requires coordination between horizontal (grip) and vertical (load) fingertip forces. Manifest Huntington's disease (HD) subjects demonstrate excessive and highly variable grip force and delayed coordination between grip and load forces. Because the onset of these impairments is unknown, we examined precision grip control in premanifest HD (pre-HD) subjects. Fifteen pre-HD and 15 age- and sex-matched controls performed the precision grip task in a seated position. Subjects grasped and lifted an object instrumented with a force transducer that measured horizontal grip and vertical load forces. Outcomes were preload time, loading time, maximum grip force, mean static grip force, and variability for all measures. We compared outcomes across groups and correlated grip measures with the Unified Huntington's Disease Rating Scale and predicted age of onset. Variability of maximum grip force (P < .0001) and variability of static grip force (P < .00001) were higher for pre-HD subjects. Preload time (P < .007) and variability of preload time (P < .006) were higher in pre-HD subjects. No differences were seen in loading time across groups. Variability of static grip force (r(2) = 0.23) and variability of preload time (r(2) = 0.59) increased with predicted onset and were correlated with tests of cognitive function. Our results indicate that pre-HD patients have poor regulation of the transition between reach and grasp and higher variability in force application and temporal coordination during the precision grip task. Force and temporal variability may be good markers of disease severity because they were correlated with predicted onset of disease. © 2011 Movement Disorder Society. PMID: 21394785 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Intravenous administration of bone marrow mesenchymal stromal cells is safe for the lung in a chronic myocardial infarction model. Regen Med. 2011 Mar;6(2):179-90 Authors: Wang W, Jiang Q, Zhang H, Jin P, Yuan X, Wei Y, Hu S Aims: Intravenous administration of bone marrow mesenchymal stromal cells (MSCs) is an attractive option for the treatment of myocardial infarction (MI). Previous studies revealed that MSC infusion could limit the deterioration of cardiac function following acute MI; however, little is known regarding the safety and efficacy of MSC infusion for chronic MI. In this study, we address cell retention after intravenous injection in a chronic MI model, and the fate and impact of distributed MSCs in the lung and heart. Methods: MI model was created by coronary ligation in female rats. A total of 3 weeks later, 5 × 10(6) bromodeoxyuridine-labeled male MSCs in 300 µl phosphate-buffered solution (PBS) were infused intravenously (cell transplantation group, n = 37). The same volume of PBS was infused and served as the control group (n = 37). A total of 20 healthy rats received intravenous PBS injections and served as the sham group. 1 day and 4 weeks after cell or PBS infusion, echocardiography was performed and cell retention was evaluated by quantitative real-time PCR. The fate of the migrated cells was detected through immunohistochemistry and the expression of inflammatory and anti-inflammatory protein was evaluated in lung and heart. The lung and heart function was also assessed. Results: 1 day after cell implantation, the percentage of retained cells relative to the initial number of injected cells in heart and lung was 0.54 ± 0.19% and 51.69 ± 12.96%, respectively. After 4 weeks, it decreased to 0.24 ± 0.09% and 0.22 ± 0.17%. The entrapped MSCs did not differentiate into alveolar epithelial-like cells. Likewise, the left ventricular function was not improved. No adverse effects on lung function were observed after cell infusion. The expression of pro-inflammatory factors, including TNF-α, IL-1β, malondialdehyde and myeloperoxidase, and anti-inflammatory factors, including TNF-α-induced protein 6, in the lung and heart was not significantly regulated after cell transplantation. Conclusion: Although the majority of intravenous infused cells were harbored in the lung, they did not cause deterioration of lung function. However, they did not activate the release of inflammatory/anti-inflammatory proteins, or stimulate angiogenesis or myogenesis in the old infarcted myocardium. Thus, intravenous administration of MSCs for chronic MI needs further experimental study. PMID: 21391852 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Isolation, cultivation and identification of adipose-derived stem cell in bovines]. Sheng Wu Gong Cheng Xue Bao. 2010 Dec;26(12):1645-51 Authors: Ren Y, Wu H, Ma Y, Cang M, Wang R, Liu D To obtain bovine adipose-derived stem cells (ADSCs), bovine ADSCs were digested in collagenase type I solution. The growth curve of ADSCs was checked by cell counting. Chromosome analysis was checked. The molecular markers of ADSCs were detected with immunofluorescence staining. The morphology of ADSCs was identical to fibroblast like and the cells showed active proliferative ability. Vimentin, CD49d and CD13 antigens were detected, but CD34 antigen was negative. Alkaline phosphatase activity was greater in ADSCs during calcification, and Alizarin Red staining was positive. Lipid droplets were apparent around cells during adipogenesis, and Oil Red-O staining was positive. The results demonstrated that ADSCs could be used as seed cells for tissue engineering due to the simple isolation, differentiation and stable and active growth. PMID: 21387826 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Authentication of human cell-based products: the role of a new consensus standard. Regen Med. 2011 Mar;6(2):255-60 Authors: Kerrigan L, Nims RW Authentication of human tissues, cell lines and primary cell cultures (including stem cell preparations) used as therapeutic modalities is often performed using phenotyping and technologies capable of assessing identity to the species level (e.g., isoenzyme analysis and/or karyotyping). This authentication paradigm alone cannot provide assurance that the correct human cell preparation is administered, so careful labeling and tracking of cells from the donor, during manufacture and as part of the final product are also employed. Precise, accurate identification of human cells to the individual donor level could, however, significantly reduce the risks of exposing human subjects to misidentified cells. The availability of a standardized method for achieving this will provide a way to improve the safety profile of human cell-based products by providing assurance that a given lot of cells originated from the intended donor and were not inadvertently mixed or replaced with cells from other donors. In support of this goal, an international team of scientists has prepared a consensus standard on authentication of human cells using short tandem repeat profiling. Associated with the standard itself will be the establishment and maintenance of a public database of short tandem repeat profiles for commonly used cell lines. PMID: 21391858 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Chemokines and inflammation in heart disease: adaptive or maladaptive? Int J Clin Exp Med. 2011;4(1):74-80 Authors: Tarzami ST Heart disease is not only the leading cause of death, disability, and healthcare expense in the US, but also the leading cause of death worldwide. Therefore, treatments to lessen ischemia-related cardiac damage could affect a broad swath of the population and have significant health and fiscal impacts. Cardiac dysfunction has been associated with elevated circulating chemokine levels, both in animals and humans. Most studies in this area have focused on chemokine expression as a prominent feature of the post-infarction inflammatory response. Such studies have investigated the role of chemokines in inflammatory leukocyte recruitment. Other work on this topic has focused on stem-cell therapy or factors e.g. chemokines mobilizing bone marrow progenitor cells as possible avenues for improving contractile dysfunction. Findings from numerous preclinical studies and several initial clinical trials support the feasibility of promoting the recruitment of bone marrow-derived cells to the infarcted heart and increased homing following injury, supporting the notion that cell therapy might have therapeutic potential. They have not, however, addressed the possibility of an autocrine/paracrine effect wherein the chemokine receptors, present on the cardiac myocyte surface, modulate functional responses to stress in which can be adaptive or maladaptive in nature. PMID: 21394288 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Conference Scene: A bright future for tissue engineering and regenerative medicine in the Asia Pacific region. Regen Med. 2011 Mar;6(2):167-70 Authors: Frith JE, Hudson JE, Cooper-White JJ The Tissue Engineering and Regenerative Medicine International Society - Asia Pacific (TERMIS-AP) annual meeting was held in Sydney, Australia from 15-17 September 2010 and highlighted the latest developments in tissue engineering and regenerative medicine in the Asia-Pacific region. Several of the plenary lectures focused on the vascularization of tissue engineering constructs, an issue that is critical for the success of larger tissue engineered constructs and was central to the meeting overall. In addition, a wide range of research also presented developments in tissue engineering for a range of body tissues (including cardiac, neural, bone, cartilage, tendon, skeletal muscle and skin), as well as advances in technologies (high-throughput screening and microfluidics). Looking more broadly, the meeting incorporated developments covering the spectrum of fundamental research through to clinical studies, with discussions on how best to direct the scientific advances being made into realistic therapies that could be made widely available in the future. Overall, the meeting highlighted the promise of early strategies, which are now showing promising results in clinical trials, and the development of a strong foundation of research from which future therapies will no doubt be developed. PMID: 21391850 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | A neural repair treatment with gait training improves motor function recovery after spinal cord injury. Conf Proc IEEE Eng Med Biol Soc. 2010;2010:5553-6 Authors: Ma C, Xu J, Cheng H, Lee YS, Lin V, He J Aimed to develop an effective approach for treating spinal cord injury (SCI), we investigated the effectiveness of a treatment strategy that combined peripheral nerve grafting, nerve growth factors and functional task based physical therapy on non-human primate models. SCI was by unilateral surgical hemi-section at the T8 spine level (approximately 4 mm gap). Two of the 4 subjects as treatment received the transplants of sural nerve segments as well as infused acidic fibroblast growth factor (aFGF) to the injured spinal cord. All four subjects received physical therapy and bipedal walking training on a treadmill to promote motor function recovery. A comprehensive evaluation system including general observation in the home cage, behavioral test and clinic score system was used to assess the effect of the treatment. The recovery of functional mobility in treated group is much faster than the control group. The treated group started to move around in their cages within a week and continued to improve in walking performance as measured by gait symmetry, while the control group developed spasticity and rigidity with a much slower and less functional recovery of mobility. All these results suggest that the treatment strategy of peripheral nerve grafting with aFGF combined with physical therapy is effective to treat SCI. PMID: 21096476 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Transplantation of tissue-engineered cartilage for the treatment of osteochondritis dissecans in the elbow: outcomes over a four-year follow-up in two patients. J Shoulder Elbow Surg. 2010 Dec;19(8):e1-6 Authors: Iwasaki N, Yamane S, Nishida K, Masuko T, Funakoshi T, Kamishima T, Minami A PMID: 20850993 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Bioengineering of dental stem cells in a PEGylated fibrin gel. Regen Med. 2011 Mar;6(2):191-200 Authors: Galler KM, Cavender AC, Koeklue U, Suggs LJ, Schmalz G, D'Souza RN Aim: Postnatal stem cells can generate tooth-specific structures after transplantation in vivo, which makes them a valuable tool for dental tissue engineering. Scaffold materials that are compatible with dental stem cells, injectable and tunable for targeted regeneration are needed. A candidate material is fibrin, a biopolymer critical to hemostasis and wound healing. Rapid degradation of fibrin can be decelerated by modification with polyethylene glycol (PEG), thus creating a hybrid material for cell delivery. The aim of this study was to evaluate the suitability of PEGylated fibrin as a scaffold for dental stem cells. Methods: A PEGylated fibrin hydrogel was combined with stem cells derived from dental pulp or periodontal ligament. Cell proliferation was assessed over a 4-week period, and alkaline phosphatase activity and expression levels of mineralization-associated genes after osteogenic induction were analyzed. Cell morphology, matrix degradation, collagen production and mineral deposition were evaluated by histology. Constructs of PEGylated fibrin with dental pulp stem cells in dentin disks were transplanted in immunocompromised mice for 5 weeks and examined for new tissue formation. Results: All cell types proliferated in PEGylated fibrin. After osteogenic induction, alkaline phosphatase activity was higher and osteoblast-specific genes were upregulated. Dentin-specific markers increased in pulp-derived stem cells. Histologic analysis revealed degradation of fibrin, production of a collagenous matrix and mineral deposition. In vivo transplantation rendered a vascularized soft connective tissue similar to dental pulp. Conclusion: Fibrin allows for the growth and differentiation of dental stem cells, can be inserted into small defects and thus appears to be a promising biomaterial for tissue regeneration in the oral cavity. PMID: 21391853 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Acknowledgements. Regen Med. 2011 Mar;6(2):261 Authors: PMID: 21391859 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Hyaluronic Acid Hydrogels for Biomedical Applications. Adv Mater. 2011 Mar 10; Authors: Burdick JA, Prestwich GD Hyaluronic acid (HA), an immunoneutral polysaccharide that is ubiquitous in the human body, is crucial for many cellular and tissue functions and has been in clinical use for over thirty years. When chemically modified, HA can be transformed into many physical forms-viscoelastic solutions, soft or stiff hydrogels, electrospun fibers, non-woven meshes, macroporous and fibrillar sponges, flexible sheets, and nanoparticulate fluids-for use in a range of preclinical and clinical settings. Many of these forms are derived from the chemical crosslinking of pendant reactive groups by addition/condensation chemistry or by radical polymerization. Clinical products for cell therapy and regenerative medicine require crosslinking chemistry that is compatible with the encapsulation of cells and injection into tissues. Moreover, an injectable clinical biomaterial must meet marketing, regulatory, and financial constraints to provide affordable products that can be approved, deployed to the clinic, and used by physicians. Many HA-derived hydrogels meet these criteria, and can deliver cells and therapeutic agents for tissue repair and regeneration. This progress report covers both basic concepts and recent advances in the development of HA-based hydrogels for biomedical applications. PMID: 21394792 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine, resource and regulation: lessons learned from the remedi project. Regen Med. 2011 Mar;6(2):241-53 Authors: Ginty PJ, Rayment EA, Hourd P, Williams DJ The successful commercialization of regenerative medicine products provides a unique challenge to the manufacturer owing to a lack of suitable investment/business models and a constantly evolving regulatory framework. The resultant slow translation of scientific discovery into safe and clinically efficacious therapies is preventing many potential products from reaching the market. This is despite of the need for new therapies that may reduce the burden on the world's healthcare systems and address the desperate need for replacement tissues and organs. The collaborative Engineering and Physical Sciences Research Council (EPSRC)-funded remedi project was devised to take a holistic but manufacturing-led approach to the challenge of translational regenerative medicine in the UK. Through strategic collaborations and discussions with industry and other academic partners, many of the positive and negative issues surrounding business and regulatory success have been documented to provide a remedi-led perspective on the management of risk in business and the elucidation of the regulatory pathways, and how the two are inherently linked. This article represents the findings from these discussions with key stakeholders and the research into best business and regulatory practices. PMID: 21391857 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Role of mechanical factors in fate decisions of stem cells. Regen Med. 2011 Mar;6(2):229-40 Authors: Li D, Zhou J, Chowdhury F, Cheng J, Wang N, Wang F Stem cells derived from adult tissues or from the inner cell mass of blastocyst-stage embryos can self-renew in culture and have the remarkable potential to undergo lineage-specific differentiation. Extensive studies have been devoted to achieving a better understanding of the soluble factors and the mechanism(s) by which they regulate the fate decisions of these cells, but it is only recently that a critical role has been revealed for physical and mechanical factors in controlling self-renewal and lineage specification. This review summarizes selected aspects of current work on stem cell mechanics with an emphasis on the influence of matrix stiffness, surface topography, cell shape and mechanical forces on the fate determination of mesenchymal stem cells and embryonic stem cells. PMID: 21391856 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Regulating interface science healthcare products: myths and uncertainties. J R Soc Interface. 2010 Dec 6;7 Suppl 6:S789-95 Authors: Bravery CA Whenever new technology emerges it brings with it concerns and uncertainties about whether or how it will need to be regulated, particularly when it is applied to human healthcare. Drawing on the recent history in the European Union (EU) of the regulation of cell-based medicinal products, and in particular tissue-engineered products, this paper explores the myths that persist around their regulation and speculates on whether the existing regulatory landscape in the EU is flexible enough to incorporate nanotechnology and other new technologies into healthcare products. By untangling these myths a number of clear conclusions are revealed that, when considered in the context of risk-benefit, make it clear that what hinders the uptake of new technology is not regulatory process but basic science. PMID: 20861040 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Enhanced bone formation in large segmental radial defects by combining adipose-derived stem cells expressing bone morphogenetic protein 2 with nHA/RHLC/PLA scaffold. Int Orthop. 2010 Dec;34(8):1341-9 Authors: Hao W, Dong J, Jiang M, Wu J, Cui F, Zhou D In this study, rabbit adipose-derived stem cells (rASCs) were isolated, cultured in vitro, and transfected with recombinant adenovirus vector containing human bone morphogenetic protein 2 (Ad-hBMP2). These cells were combined with a nano-hydroxyapatite/recombinant human-like collagen/poly(lactic acid) scaffold (nHA/RHLC/PLA) to fabricate a new biocomposite (hBMP2/rASCs-nHA/RHLC/PLA, group 1) and cultured in osteogenic medium. Non-transfected rASCs mixed with nHA/RHLC/PLA (rASCs-nHA/RHLC/PLA, group 2) and nHA/RHLC/PLA scaffold alone (group 3) served as controls. Scanning electron microscope (SEM) demonstrated integration of rASCs with the nHA/RHLC/PLA scaffold. Quantitative real-time RT-PCR analyses of collagen I, osteonectin, and osteopontin cDNA expression indicated that the osteogenic potency of rASCs was enhanced by transfection with Ad-hBMP2. After in vitro culture for seven days, three groups were implanted into 15-mm length critical-sized segmental radial defects in rabbits. After 12 weeks, radiographic and histological analyses were performed. In group 1, the medullary cavity was recanalised, bone was rebuilt and moulding was finished, the bone contour had begun to remodel and scaffold was degraded completely. In contrast, bone defects were not repaired in groups 2 or 3. Furthermore, the scaffold degradation rate in group 1 was significantly higher than in groups 2 or 3. In summary, after transduction with Ad-hBMP2, the osteogenesis of rASCs was enhanced; a new biocomposite created with these cells induced repair of a critical bone defect in vivo in a relatively short time. PMID: 20140671 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Translation and commercialization of regenerative medicines. J R Soc Interface. 2010 Dec 6;7 Suppl 6:S675-6 Authors: Polak J, Bravery CA, Prescott C PMID: 20926428 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Tumorigenicity of pluripotent stem cells: biological insights from molecular imaging. J R Soc Interface. 2010 Dec 6;7 Suppl 6:S753-63 Authors: Kooreman NG, Wu JC Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the ability (i) to duplicate indefinitely while maintaining pluripotency and (ii) to differentiate into cell types of all three embryonic germ layers. These two properties of ESCs and iPSCs make them potentially suitable for tissue engineering and cell replacement therapy for many different diseases, including Parkinson's disease, diabetes and heart disease. However, one critical obstacle in the clinical application of ESCs or iPSCs is the risk of teratoma formation. The emerging field of molecular imaging is allowing researchers to track transplanted ESCs or iPSCs in vivo, enabling early detection of teratomas. PMID: 20880852 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Alignment hierarchies: engineering architecture from the nanometre to the micrometre scale. J R Soc Interface. 2010 Dec 6;7 Suppl 6:S707-16 Authors: Kureshi A, Cheema U, Alekseeva T, Cambrey A, Brown R Natural tissues are built of metabolites, soluble proteins and solid extracellular matrix components (largely fibrils) together with cells. These are configured in highly organized hierarchies of structure across length scales from nanometre to millimetre, with alignments that are dominated by anisotropies in their fibrillar matrix. If we are to successfully engineer tissues, these hierarchies need to be mimicked with an understanding of the interaction between them. In particular, the movement of different elements of the tissue (e.g. molecules, cells and bulk fluids) is controlled by matrix structures at distinct scales. We present three novel systems to introduce alignment of collagen fibrils, cells and growth factor gradients within a three-dimensional collagen scaffold using fluid flow, embossing and layering of construct. Importantly, these can be seen as different parts of the same hierarchy of three-dimensional structure, as they are all formed into dense collagen gels. Fluid flow aligns collagen fibrils at the nanoscale, embossed topographical features provide alignment cues at the microscale and introducing layered configuration to three-dimensional collagen scaffolds provides microscale- and mesoscale-aligned pathways for protein factor delivery as well as barriers to confine protein diffusion to specific spatial directions. These seemingly separate methods can be employed to increase complexity of simple extracellular matrix scaffolds, providing insight into new approaches to directly fabricate complex physical and chemical cues at different hierarchical scales, similar to those in natural tissues. PMID: 20926429 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses. Int Orthop. 2011 Mar 11; Authors: Torricelli P, Fini M, Filardo G, Tschon M, Pischedda M, Pacorini A, Kon E, Giardino R PURPOSE: Tissue repair in musculoskeletal injuries is often a slow and sometimes incomplete process. Regenerative medicine based on the use of growth factors (GFs) and cell therapy is aimed at improving the quality and speed of tendon and ligament healing. The aim of this study was to evaluate the potential for the administration of a combination of autologous platelet-rich plasma (PRP) and freshly isolated bone marrow mononucleated cells (BMMNCs) in 13 competition horses affected by overuse musculoskeletal injuries (suspensory ligament desmopathy and superficial flexor tendinopathy) and refractory to other therapies. METHODS: After ultrasonographic localisation of the lesion, the autologous BMMNC suspension and PRP were injected directly into the core lesion. BMMNC and platelet count as well as growth factors in PRP were measured to determine factors influencing the clinical outcome. RESULTS: Horses showed a marked improvement in their degree of lameness and 84.6% were able to return to competition. Among all the factors studied, the platelet concentration predicted the healing time: significantly faster recovery (p = 0.049) was observed in cases of PRP with more than 750 × 10(3)/μl platelets. CONCLUSIONS: Competition horses are involved in highly demanding activities, thus being a similar model for the high mechanical overload typical of human athletes. The promising results obtained suggest that this combined biological approach may be useful even for the treatment of recalcitrant overuse musculoskeletal injuries in highly demanding patients if the appropriate dose of cells and GFs is applied. PMID: 21394594 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Autologous periodontal ligament cells in the treatment of class II furcation defects: a study in dogs. J Clin Periodontol. 2011 Mar 11; Authors: Suaid FF, Ribeiro FV, Rodrigues TL, Silvério KG, Carvalho MD, Nociti FH, Casati MZ, Sallum EA Suaid FF, Ribeiro FV, Rodrigues TL, Silvério KG, Carvalho MD, Nociti Jr. FH, Casati MZ, Sallum EA: Autologous periodontal ligament cells in the treatment of class II furcation defects: a study in dogs. J Clin Periodontol 2011; doi: 10.1111/j.1600-051X.2010.01715.x ABSTRACT: Aim: The goal of this study was to histologically investigate the use of periodontal ligament cells (PDL cells) in tissue engineering to regenerate class II furcation defects. Material and Methods: PDL cells were obtained from the mandibular tooth extracted from each dog (seven), cultured in vitro and phenotypically characterized with regard to their biological properties. Following, bilateral class II furcation lesions were created at maxillary 3rd premolars and were randomly assigned to the test group [PDL cells+guided tissue regeneration (GTR)] or the control group (GTR). After 3 months, the animals were euthanized to evaluate the histometric parameters. Results: In vitro, PDL cells were able to promote mineral nodule formation and to express bone sialoprotein, type I collagen and alkaline phosphatase. Histometrically, data analysis demonstrated that the cell-treated group presented a superior length of new cementum (6.00 ± 1.50 and 8.08 ± 1.08 mm), a greater extension of periodontal regeneration (3.94 ± 1.20 and 7.28 ± 1.00 mm), a lower formation of connective tissue/epithelium (2.15 ± 1.92 and 0.60 ± 0.99 mm), a larger area of new bone (7.01 ± 0.61 and 9.02 ± 2.30 mm(2) ) and a smaller area of connective tissue/epithelium (5.90 ± 1.67 and 4.22 ± 0.95 mm(2) ), when compared with control group. Conclusion: PDL cells in association with GTR may significantly promote periodontal regeneration in class II furcation defects in dog. PMID: 21392047 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stem cell technology for the study and treatment of motor neuron diseases. Regen Med. 2011 Mar;6(2):201-13 Authors: Lunn JS, Sakowski SA, Federici T, Glass JD, Boulis NM, Feldman EL Amyotrophic lateral sclerosis and spinal muscular atrophy are devastating neurodegenerative diseases that lead to the specific loss of motor neurons. Recently, stem cell technologies have been developed for the investigation and treatment of both diseases. Here we discuss the different stem cells currently being studied for mechanistic discovery and therapeutic development, including embryonic, adult and induced pluripotent stem cells. We also present supporting evidence for the utilization of stem cell technology in the treatment of amyotrophic lateral sclerosis and spinal muscular atrophy, and describe key issues that must be considered for the transition of stem cell therapies for motor neuron diseases from bench to bedside. Finally, we discuss the first-in-human Phase I trial currently underway examining the safety and feasibility of intraspinal stem cell injections in amyotrophic lateral sclerosis patients as a foundation for translating stem cell therapies for various neurological diseases. PMID: 21391854 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Stem cells from adipose tissue. Cell Mol Biol Lett. 2011 Mar 9; Authors: Witkowska-Zimny M, Walenko K This is a review of the growing scientific interest in the developmental plasticity and therapeutic potential of stromal cells isolated from adipose tissue. Adipose-derived stem/stromal cells (ASCs) are multipotent somatic stem cells that are abundant in fat tissue. It has been shown that ASCs can differentiate into several lineages, including adipose cells, chondrocytes, osteoblasts, neuronal cells, endothelial cells, and cardiomyocytes. At the same time, adipose tissue can be harvested by a minimally invasive procedure, which makes it a promising source of adult stem cells. Therefore, it is believed that ASCs may become an alternative to the currently available adult stem cells (e.g. bone marrow stromal cells) for potential use in regenerative medicine. In this review, we present the basic information about the field of adipose-derived stem cells and their potential use in various applications. PMID: 21394447 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal stem cells display different gene expression profiles compared to hyaline and elastic chondrocytes. Int J Clin Exp Med. 2011;4(1):81-90 Authors: Zhai LJ, Zhao KQ, Wang ZQ, Feng Y, Xing SC Cartilage has a poor intrinsic repair capacity, requiring surgical intervention to effect biological repair. Tissue engineering technologies or regenerative medicine strategies are currently being employed to address cartilage repair. Mesenchymal stem cells (MSCs) are considered to be an excellent cell source for this application. However, the different gene expression profiles between the MSCs and differentiated cartilage remain unclear. In this report, we first examined the gene expression profiles between the MSCs, hyaline and elastic chondrocytes, and then identify candidate genes, which may be important in the process of MSC differentiation into hyaline and elastic cartilage. Several hundred differentially expressed genes were screened initially by microarray, including 417 simultaneously up-regulated genes in both hyaline and elastic chondrocytes, with 313 down-regulated genes. Several genes were identified that were up-regulated in hyaline chondrocytes while down-regulated in elastic chondrocytes. Both RT-PCR and western blot analysis were consistent with those results obtained by microarray analysis. Chondromodulinl (Chm1) was found to be highly expressed in MSCs differentiating to hyaline and elastic cartilage. Both collagen type II, alpha 1 (Col2a1) and cartilage homeo protein 1 (Cart1) were also highly upregulated and may be important early differentiation of MSCs to hyaline cartilage. PMID: 21394289 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Interview: The story of Advanced BioHealing: commercializing bioengineered tissue products. Regen Med. 2011 Mar;6(2):157-61 Authors: Tozer D Dean Tozer is Senior Vice President at Advanced BioHealing, Inc. (ABH), overseeing marketing, corporate development, government affairs, product development, various regulatory functions and international expansion. After completing his Bachelor of Commerce from Saint Mary's University in Halifax, Canada, Mr Tozer spent 10 years in the global pharmaceutical industry, primarily with G.D. Searle (a division of Monsanto) where he had a wide variety of roles in Global Marketing, Sales, Business Redesign, and Accounting and Finance. Mr Tozer then worked as a consultant to the biopharmaceutical industry, assisting start-up organizations in developing commercial strategies for both pharmaceutical products and biomedical devices, prior to joining ABH in March 2006 as Vice President of Marketing & Corporate Development. In addition to his leadership role at ABH, Mr Tozer currently serves as an officer and board member for the Alliance for Regenerative Medicine, a Washington DC-based organization formed to advance regenerative medicine by representing and supporting the community of companies, academic research institutions, patient advocacy groups, foundations, and other organizations before the Congress, federal agencies and the general public. PMID: 21391848 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Human endothelial stem/progenitor cells, angiogenic factors and vascular repair. J R Soc Interface. 2010 Dec 6;7 Suppl 6:S731-51 Authors: Watt SM, Athanassopoulos A, Harris AL, Tsaknakis G Neovascularization or new blood vessel formation is of utmost importance not only for tissue and organ development and for tissue repair and regeneration, but also for pathological processes, such as tumour development. Despite this, the endothelial lineage, its origin, and the regulation of endothelial development and function either intrinsically from stem cells or extrinsically by proangiogenic supporting cells and other elements within local and specific microenvironmental niches are still not fully understood. There can be no doubt that for most tissues and organs, revascularization represents the holy grail for tissue repair, with autologous endothelial stem/progenitor cells, their proangiogenic counterparts and the products of these cells all being attractive targets for therapeutic intervention. Historically, a great deal of controversy has surrounded the identification and origin of cells and factors that contribute to revascularization, the use of such cells or their products as biomarkers to predict and monitor tissue damage and repair or tumour progression and therapeutic responses, and indeed their efficacy in revascularizing and repairing damaged tissues. Here, we will review the role of endothelial progenitor cells and of supporting proangiogenic cells and their products, principally in humans, as diagnostic and therapeutic agents for wound repair and tissue regeneration. PMID: 20843839 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Applying macromolecular crowding to enhance extracellular matrix deposition and its remodeling in vitro for tissue engineering and cell-based therapies. Adv Drug Deliv Rev. 2011 Mar 7; Authors: Chen C, Loe F, Blocki A, Peng Y, Raghunath M With the advent of multicellular organisms, the exterior of cells evolved dramatically from highly aqueous surroundings into an extracellular matrix and space crowded with macromolecules. Cell-based therapies require removal of cells from their crowded physiological context and propagating them in dilute culture medium to attain therapeutically relevant numbers whilst preserving their phenotype. However, bereft of their microenvironment, cells under perform and lose functionality. Major efforts currently aim to modify cell culture surfaces and build three dimensional scaffolds to improve this situation. We discuss here alternative strategies that enable cells to re-create their own microenvironment in vitro, using carbohydrate-based macromolecules as culture media additives that create an excluded volume effect at defined fraction volume occupancies. This biophysical approach dramatically enhances extracellular matrix deposition by differentiated cells and stem cells, and boosts progenitor cell differentiation and proliferation. We begin to understand how well cells really can perform ex vivo if given the chance. PMID: 21392551 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | News & views in ... Regenerative medicine. Regen Med. 2011 Mar;6(2):141-4 Authors: PMID: 21391846 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Corrigendum. Regen Med. 2011 Mar;6(2):264 Authors: PMID: 21391860 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | Regenerative Medicine , March 2011, Vol. 6, No. 2, Pages 179-190.
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