| IL-6 adsorption dynamics in hemoadsorption beads studied using confocal laser scanning microscopy.
November 12, 2009 at 10:00 am
|
| | IL-6 adsorption dynamics in hemoadsorption beads studied using confocal laser scanning microscopy. J Biomed Mater Res B Appl Biomater. 2009 Nov 10; Authors: Kimmel JD, Gibson GA, Watkins SC, Kellum JA, Federspiel WJ Sepsis is characterized by a systemic inflammatory response caused by infection, and can result in organ failure and death. Removal of inflammatory mediators such as cytokines from the circulating blood is a promising treatment for severe sepsis. We are developing an extracorporeal hemoadsorption device to remove cytokines from the blood using biocompatible, polymer sorbent beads. In this study, we used confocal laser scanning microscopy (CLSM) to directly examine adsorption dynamics of a cytokine (IL-6) within hemoadsorption beads. Fluorescently labeled IL-6 was incubated with sorbent particles, and CLSM was used to quantify spatial adsorption profiles of IL-6 within the sorbent matrix. IL-6 adsorption was limited to the outer 15 mum of the sorbent particle over a relevant clinical time period, and intraparticle adsorption dynamics was modeled using classical adsorption/diffusion mechanisms. A single model parameter, alpha = q(max) K/D, was estimated by fitting CLSM intensity profiles to our mathematical model, where q(max) and K are Langmuir adsorption isotherm parameters, and D is the effective diffusion coefficient of IL-6 within the sorbent matrix. Given the large diameter of our sorbent beads (450 mum), less than 20% of available sorbent surface area participates in cytokine adsorption. Development of smaller beads may accelerate cytokine adsorption by maximizing available surface area per bead mass. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID: 19904819 [PubMed - as supplied by publisher] |
| Challenges of Stem Cell Therapy for Spinal Cord Injury: Human Embryonic Stem Cells, Endogenous Neural Stem Cells or Induced Pluripotent Stem Cells?
November 12, 2009 at 10:00 am
|
| | Challenges of Stem Cell Therapy for Spinal Cord Injury: Human Embryonic Stem Cells, Endogenous Neural Stem Cells or Induced Pluripotent Stem Cells? Stem Cells. 2009 Nov 10; Authors: Ronaghi M, Erceg S, Moreno-Manzano V, Stojkovic M Spinal cord injury (SCI) causes myelopathy, damage to white matter and myelinated fiber tracts that carry sensation and motor signals to and from the brain. The gray matter damage causes segmental losses of interneurons and motorneurons and restricts therapeutic options. Recent advances in stem cell biology, neural injury and repair, and the progress towards development of neuroprotective and regenerative interventions are the basis for increased optimism. This review summarizes the pathophysiological mechanisms following SCI and compares human embryonic, adult neural and the induced pluripotent stem cell-based therapeutic strategies for SCI.A brief summary of pathophysiological events following spinal cord injury. PMID: 19904738 [PubMed - as supplied by publisher] |
| Serum-free, xeno-free culture media maintain the proliferation rate and multipotentiality of adipose stem cells in vitro.
November 12, 2009 at 10:00 am
|
| | Serum-free, xeno-free culture media maintain the proliferation rate and multipotentiality of adipose stem cells in vitro. Cytotherapy. 2009 Nov 10;11(7):958-972 Authors: Lindroos B, Boucher S, Chase L, Kuokkanen H, Huhtala H, Haataja R, Vemuri M, Suuronen R, Miettinen S Background aims Human adipose stem cells (ASC) are an abundant, readily available population of multipotent progenitor cells that reside in adipose tissue. ASC have been shown to have therapeutic applicability in pre-clinical studies, but a standardized expansion method for clinical cell therapy has yet to be established. Isolated ASC are typically expanded in medium containing fetal bovine serum (FBS); however, sera and other culturing reagents of animal origin in clinical therapy pose numerous safety issues, including possible infections and severe immune reactions. Methods To identify optimal conditions for ex vivo expansion of ASC, the effects of seven serum-free (SF) and xeno-free (XF) media were investigated with both FBS and allogeneic human serum (alloHS; as a control media). Surface marker expression, proliferation, morphology and differentiation analyzes were utilized for investigating the effects of media on ASC. Results The proliferation and morphology analysis demonstrated significant differences between ASC cultured in SF/XF culture media compared with serum-containing culture media, with medium prototype STEMPRO((R)) MSC SFM XF providing significantly higher proliferation rates than ASC cultured in media containing serum, while still maintaining the differentiation potential and surface marker expression profile characteristic of ASC. Conclusions Looking forward, fully defined XF media formulations will provide the means for the development and approval of safer clinical cell therapy treatments. However, to fully recognize the capacity of these XF culture media, further pre-clinical safety and efficacy studies must be performed. PMID: 19903107 [PubMed - as supplied by publisher] |
| Harvesting human adipose tissue-derived adult stem cells: resection versus liposuction.
November 12, 2009 at 10:00 am
|
| | Harvesting human adipose tissue-derived adult stem cells: resection versus liposuction. Cytotherapy. 2009 Nov 10;11(7):947-957 Authors: Schreml S, Babilas P, Fruth S, Orsó E, Schmitz G, Mueller MB, Nerlich M, Prantl L Abstract Background Adipose tissue is an abundant source of mesenchymal stem cells (MSC), which can be used for tissue-engineering purposes. The aim of our study was to determine the more suitable procedure, surgical resection or liposuction, for harvesting human adipose tissue-derived stem cells (hASC) with regard to viability, cell count and differentiation potential. Methods After harvesting hASC, trypan blue staining and cell counting were carried out. Subsequently, hASC were cultured, analyzed by fluorescence-activated cell sorting (FACS) and differentiated under adipogenic, osteogenic and chondrogenic conditions. Histologic and functional analyzes were performed at the end of the differentiation period. Results No significant difference was found with regard to the cell counts of hASC from liposuction and surgically resected material (P=0.086). The percentage of viable cells was significantly higher for liposuction aspirates than for resection material (P=0.002). No significant difference was found in the adipogenic differentiation potential (P=0.179). A significantly lower number of cultures obtained from liposuction material than from resection material could be differentiated into osteocytes (P=0.049) and chondrocytes (P=0.012). Discussion Even though some lineages from lipoaspirated hASC can not be differentiated as frequently as those from surgically resected material, liposuction may be superior for some tissue-engineering purposes, particularly because of the less invasive harvesting procedure, the higher percentage of viable cells and the fact that there is no significant difference between lipoaspirated and resected hASC with regard to adipogenic differentiation potential. PMID: 19903106 [PubMed - as supplied by publisher] |
| Novel Freeze-drying Methods to Produce a Range of Collagen-GAG scaffolds with Tailored Mean Pores Sizes.
November 12, 2009 at 10:00 am
|
| | Novel Freeze-drying Methods to Produce a Range of Collagen-GAG scaffolds with Tailored Mean Pores Sizes. Tissue Eng Part C Methods. 2009 Nov 10; Authors: Haugh MG, Murphy CM, Obrien FJ The pore structure of 3-D scaffolds used in tissue engineering has been shown to significantly influence cellular activity. As the optimal pore size is dependant on the specifics of the tissue engineering application, the ability to alter the pore size over a wide range is essential for a particular scaffold to be suitable for multiple applications. With this in mind, the aim of this study was to develop methodologies to produce a range of collagen-glycosaminoglycan (CG) scaffolds with tailored mean pore sizes. The pore size of CG scaffolds is established during the freeze-drying fabrication process. In this study, freezing temperature (Tf) was varied (-10 to -70 degrees C) and an annealing step was introduced to the process in order to determine their effects on pore size. Annealing is an additional step in the freeze-drying cycle which involves raising the temperature of the frozen suspension in order to increase the rate of ice crystal growth. The results show that the pore size of the scaffolds decreased with as the Tf was reduced. Additionally, the introduction of an annealing step during freeze-drying was found to result in a significant increase (40%) in pore size. Taken together, these results demonstrate that the methodologies developed in this study can be used to produce a range of CG scaffolds with mean pore sizes from 85 to 325 microm. This is a substantial improvement on the range of pore sizes that it was possible to produce previously (96-150 microm). The methods developed in this study provide a basis for the investigation of the effects of pore size on both in vitro and in vivo performance, and the determination of the optimal pore structure for specific tissue engineering applications. PMID: 19903089 [PubMed - as supplied by publisher] |
| Effect of matrix elasticity on the maintenance of the chondrogenic phenotype.
November 12, 2009 at 10:00 am
|
| | Effect of matrix elasticity on the maintenance of the chondrogenic phenotype. Tissue Eng Part A. 2009 Nov 10; Authors: Schuh E, Kramer J, Rohwedel J, Notbohm H, Müller R, Gutsmann T, Rotter N The aim of this study was to examine the influence of matrix elasticity on the maintenance of the chondrogenic phenotype of chondrocytes cultured in monolayer. We used a 2D-culturing-system in which polyacrylamide gels with different concentrations of BIS-Acrylamide were coated with collagen type I. Matrices with a Young's Modulus of 4 kPa, 10 kPa, 40 kPa, and 100 kPa were produced, as determined by atomic force microscopy. Porcine chondrocytes were cultivated on these matrices at low density for seven days. The proliferation of cells was analyzed by 5-Bromo-2'-deoxy-uridine (BrdU) incorporation. Maintenance of the chondrogenic phenotype was analyzed by measuring collagen type I, type II and aggrecan gene expression, immunofluorescence staining for collagen type II, and phalloidin staining for actin filaments. Cellular proliferation and actin organisation was decreased on matrices of 4 kPa, in comparison to stiffer substrates. The differentiated phenotype of the chondrocytes grown on matrices of 4 kPa was stabilized, indicated by higher collagen type II and aggrecan, and lower collagen type I expression. These findings indicate that chondrocytes sense the elasticity of the matrix and might be used for the design of scaffolds with mechanical properties, specifically tailored to support the chondrogenic phenotype in tissue engineering applications. PMID: 19903088 [PubMed - as supplied by publisher] |
| New Challenges for Intervertebral Disc Treatment using Regenerative Medicine.
November 12, 2009 at 10:00 am
|
| | New Challenges for Intervertebral Disc Treatment using Regenerative Medicine. Tissue Eng Part B Rev. 2009 Nov 10; Authors: Masuda K, Lotz J The development of tissue engineering therapies for the intervertebral disc is challenging due to ambiguities of disease and pain mechanisms in patients, and lack of consensus on pre-clinical models for safety and efficacy testing. While the issues associated with model selection for studying orthopaedic diseases or treatments has been discussed often, the multi-faceted challenges associated with developing intervertebral disc tissue engineering therapies requires special discussion. This review covers topics relevant to the clinical translation of tissue-engineered technologies: 1) the unmet clinical need; 2) appropriate models for safety and efficacy testing; 3) the need for standardized model systems; and 4) the translational pathways leading to a clinical trial. For pre-clinical evaluation of new therapies, we recommend establishing biologic plausibility of efficacy and safety using models of increasing complexity, starting with cell culture, small animals (rats and rabbits), then large animals (goat and mini-pig) that more closely mimic nutritional, biomechanical, and surgical realities of human application. The use of standardized and reproducible experimental procedures and outcome measures is critical for judging relative efficacy. Finally, success will hinge on carefully designed clinical trials with well-defined patient selection criteria, gold-standard controls, and objective outcome metrics to assess performance in the early post-operative period. PMID: 19903086 [PubMed - as supplied by publisher] |
| Functional properties of cell-seeded three-dimensionally woven poly(epsilon-caprolactone) scaffolds for cartilage tissue engineering.
November 12, 2009 at 10:00 am
|
| | Functional properties of cell-seeded three-dimensionally woven poly(epsilon-caprolactone) scaffolds for cartilage tissue engineering. Tissue Eng Part A. 2009 Nov 10; Authors: Moutos F, Guilak F Articular cartilage possesses complex mechanical properties that provide healthy joints the ability to bear repeated loads and maintain smooth articulating surfaces over an entire lifetime. In this study, we utilized a fiber-reinforced composite scaffold designed to mimic the anisotropic, nonlinear, and viscoelastic biomechanical characteristics of native cartilage as the basis for developing functional tissue-engineered constructs. Three-dimensionally (3-D) woven poly (epsilon-caprolactone) (PCL) scaffolds were encapsulated with a fibrin hydrogel, seeded with human adipose-derived stem cells (ASCs), and cultured for 28 days in chondrogenic culture conditions. Compressive and shear biomechanical testing showed that PCL-based constructs maintained their mechanical properties relative to baseline throughout the culture period, while supporting the synthesis of a collagen-rich extracellular matrix. Furthermore, constructs displayed an equilibrium coefficient of friction similar to that of native articular cartilage (mueq ~ 0.1 - 0.3) over the prescribed culture period. Our findings show that 3-D PCL/fibrin composite scaffolds can be produced with cartilage-like mechanical properties, and that these engineered properties can be maintained in culture while seeded stem cells regenerate a new, functional tissue construct. PMID: 19903085 [PubMed - as supplied by publisher] |
| Acknowledgements.
November 12, 2009 at 10:00 am
|
| | Acknowledgements. Regen Med. 2009 Nov;4(6):931 Authors: PMID: 19903009 [PubMed - as supplied by publisher] |
| Stem cells and regenerative medicine on the Asian horizon: an economic, industry and social perspective.
November 12, 2009 at 10:00 am
|
| | Stem cells and regenerative medicine on the Asian horizon: an economic, industry and social perspective. Regen Med. 2009 Nov;4(6):911-918 Authors: Sipp D For the past decade, forays into stem cell research and regenerative medicine by institutes and companies based in the Asia-Pacific region have attracted global attention at levels unprecedented in the life sciences. The unique combination of economic pressures, competitiveness and opportunism, laissez-faire regulation, burgeoning investment in the life sciences and rapidly growing markets, coupled with its great diversity, have propelled the region to surge forward in some areas, but to stumble in others. This article provides a historical and scientific context to the state of stem cell research and clinical applications in the region, and highlights trends and new possibilities to watch for on the Asian horizon. PMID: 19903008 [PubMed - as supplied by publisher] |
| Human embryonic stem cells and genomic instability.
November 12, 2009 at 10:00 am
|
| | Human embryonic stem cells and genomic instability. Regen Med. 2009 Nov;4(6):899-909 Authors: Lefort N, Perrier AL, Laâbi Y, Varela C, Peschanski M Owing to their original properties, pluripotent human embryonic stem cells (hESCs) and their progenies are highly valuable not only for regenerative medicine, but also as tools to study development and pathologies or as cellular substrates to screen and test new drugs. However, ensuring their genomic integrity is one important prerequisite for both research and therapeutic applications. Until recently, several studies about the genomic stability of cultured hESCs had described chromosomal or else large genomic alterations detectable with conventional karyotypic methods. In the past year, several laboratories have reported many small genomic alterations, in the megabase-sized range, using more sensitive karyotyping methods, showing that hESCs are prone to acquire focal genomic abnormalities in culture. As these alterations were found to be nonrandom, these findings strongly advocate for high-resolution monitoring of human pluripotent stem cell lines, especially when intended to be used for clinical applications. PMID: 19903007 [PubMed - as supplied by publisher] |
| Diverse roles of the vasculature within the neural stem cell niche.
November 12, 2009 at 10:00 am
|
| | Diverse roles of the vasculature within the neural stem cell niche. Regen Med. 2009 Nov;4(6):879-897 Authors: Goldberg JS, Hirschi KK An interdependent relationship between the vascular and nervous systems begins during the earliest stages of development and persists through the mammalian lifespan. Accordingly, the process of adult neurogenesis involves the coordinated response of both systems to maintain a specialized microenvironment (niche) that tips the scale towards maintenance or regeneration, as needed. Understanding the nature and regulation of this balance will provide a foundation on which the potential for molecular- and stem cell-based therapies can be developed to treat prevalent CNS diseases and disorders. The vasculature is cited as a prominent feature within the adult subventricular zone and subgranular zone, known adult neural stem cell niches, helping to retain neural stem and progenitor cell potential. The vascular compartment within the neural stem cell niche has the unique opportunity to not only regulate neural stem and progenitor cells through direct contact with, and paracrine signaling from, endothelial and mural cells that make up blood vessels, but also integrates systemic signals into the local microenvironment via distribution of soluble factors from blood circulation to regulate stem cell niche behavior. Understanding the intricate role that the vasculature plays to influence neural stem cells in the context of niche regulation will help to bridge the gap from bench to bedside for the development of regeneration-based therapies for the CNS. PMID: 19903006 [PubMed - as supplied by publisher] |
| Engineering the CNS stem cell microenvironment.
November 12, 2009 at 10:00 am
|
| | Engineering the CNS stem cell microenvironment. Regen Med. 2009 Nov;4(6):865-877 Authors: Williams CA, Lavik EB The loss of neural tissue underlies the symptomatology of several neurological insults of disparate etiology, including trauma, cerebrovascular insult and neurodegenerative disease. Restoration of damaged neural tissue through the use of exogenous or endogenous neural stem or progenitor cells is an enticing therapeutic option provided one can control their proliferation, migration and differentiation. Initial attempts at CNS tissue engineering relied on the intrinsic cellular properties of progenitor cells; however, it is now appreciated that the microenvironment surrounding the cells plays an indispensible role in regulating stem cell behavior. This article focuses on attempts to engineer the neural stem cell microenvironment by utilizing the major cellular components of the niche (endothelial cells, astrocytes and ependymal cells) and the extracellular matrix in which they are embedded. PMID: 19903005 [PubMed - as supplied by publisher] |
| Using stem cells to mend the retina in ocular disease.
November 12, 2009 at 10:00 am
|
| | Using stem cells to mend the retina in ocular disease. Regen Med. 2009 Nov;4(6):855-864 Authors: Bull ND, Martin KR Retinal degenerative diseases are the leading cause of incurable blindness worldwide. Furthermore, existing pharmacological and surgical interventions are only partially effective in halting disease progression, thus adjunctive neuroprotective strategies are desperately needed to preserve vision. Stem cells appear to possess inherent neuroprotective abilities, at least in part by providing neurotrophic support to injured neurons. Advances in stem cell biology offer the hope of new therapies for a broad range of neurodegenerative conditions, including those of the retina. Experimental cell-mediated therapies also hint at the tantalizing possibility of achieving retinal neuronal replacement and regeneration, once cells are lost to the disease process. This article summarizes the latest advances in cell therapies for neuroprotection and regeneration in neurodegenerative pathologies of both the inner and outer retina. PMID: 19903004 [PubMed - as supplied by publisher] |
| Assessing the value of autologous and allogeneic cells for regenerative medicine.
November 12, 2009 at 10:00 am
|
| | Assessing the value of autologous and allogeneic cells for regenerative medicine. Regen Med. 2009 Nov;4(6):835-853 Authors: Mason C, Dunnill P The advantages and disadvantages of autologous and allogeneic human cells for regenerative medicine are summarized. The comparison of relative advantages includes: ease and cost of treating large numbers of patients, the speed of availability of therapy and the differing complexity of the development pathways. The comparison of relative disadvantages deals with issues such as variability of source material, the risks of cell abnormality and of viral and prion contamination, and the sensitive issues surrounding use of embryo-derived cells. From the comparisons, several potentially decisive issues are drawn out, such as possible immune response and teratoma formation, the impact of patents and the virtues of hospital versus industry-centered development. PMID: 19903003 [PubMed - as supplied by publisher] |
| Cardiac stem cell genetic engineering using the alphaMHC promoter.
November 12, 2009 at 10:00 am
|
| | Cardiac stem cell genetic engineering using the alphaMHC promoter. Regen Med. 2009 Nov;4(6):823-833 Authors: Bailey B, Izarra A, Alvarez R, Fischer KM, Cottage CT, Quijada P, Díez-Juan A, Sussman MA Aims: Cardiac stem cells (CSCs) show potential as a cellular therapeutic approach to blunt tissue damage and facilitate reparative and regenerative processes after myocardial infarction. Despite multiple published reports of improvement, functional benefits remain modest using normal stem cells delivered by adoptive transfer into damaged myocardium. The goal of this study is to enhance survival and proliferation of CSCs that have undergone lineage commitment in early phases as evidenced by expression of proteins driven by the alpha-myosin heavy chain (alphaMHC) promoter. The early increased expression of survival kinases augments expansion of the cardiogenic CSC pool and subsequent daughter progeny. Materials & methods: Normal CSCs engineered with fluorescent reporter protein constructs under control of the alphaMHC promoter show transgene protein expression, confirming activity of the promoter in CSCs. Cultured CSCs from both nontransgenic and cardiac-specific transgenic mice expressing survival kinases driven by the alphaMHC promoter were analyzed to characterize transgene expression following treatments to promote differentiation in culture. Results & conclusion: Therapeutic genes controlled by the alphaMHC promoter can be engineered into and expressed in CSCs and cardiomyocyte progeny with the goal of improving the efficacy of cardiac stem cell therapy. PMID: 19903002 [PubMed - as supplied by publisher] |
| Plasticity of stem cells derived from adult periodontal ligament.
November 12, 2009 at 10:00 am
|
| | Plasticity of stem cells derived from adult periodontal ligament. Regen Med. 2009 Nov;4(6):809-821 Authors: Huang CY, Pelaez D, Bendala JD, Garcia-Godoy F, Cheung HS Background: The neural crest contains pluripotent cells that can give rise to neurons and glial cells of the peripheral nervous system, endocrine cells, connective tissue cells, muscle cells and pigment cells during embryonic development. Stem cells derived from the neural crest may still reside in neural crest derivatives including the periodontal ligament (PDL). However, the pluripotency of PDL-derived stem cells has not been investigated. Aim: To identify subpopulations of stem cells from the adult PDL and study their pluripotency. Human PDLs were harvested from impacted wisdom teeth (patients aged 19-22 years). Results: This study demonstrated that subpopulations of PDL cells expressed embryonic stem cell markers (Oct4, Sox2, Nanog and Klf4) and a subset of neural crest markers (Nestin, Slug, p75 and Sox10). Such PDL cell subpopulations exhibited the potential to differentiate into neurogenic, cardiomyogenic, chondrogenic and osteogenic lineages. Furthermore, preliminary evidence suggesting insulin production of PDL cells might be indicative of the generation of cells of the endodermal lineage. Conclusion: These findings suggest that the PDL may contain pluripotent stem cells that originate from the neural crest. Our observations open the door to prospective autologous therapeutic applications for a variety of conditions. PMID: 19903001 [PubMed - as supplied by publisher] |
| Research Highlights.
November 12, 2009 at 10:00 am
|
| | Research Highlights. Regen Med. 2009 Nov;4(6):805-807 Authors: Kusuma S, Gerecht S PMID: 19903000 [PubMed - as supplied by publisher] |
| Business Development.
November 12, 2009 at 10:00 am
|
| | Business Development. Regen Med. 2009 Nov;4(6):797-804 Authors: Ilic D PMID: 19902999 [PubMed - as supplied by publisher] | |
No comments:
Post a Comment