|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | The siren call of the sea is being heard once again. We are raising anchor to continue our journey to Panama from our current location in Puerto Jimenez in Costa Rica. The California Stem Cell Report will go dark, so to speak, until we find another Internet connection, which could range from a few days to about two weeks. Rest assured – or not so assured – that postings will resume in the | | | | | | | | | | | | | | | | | | | | | | | | The longstanding issues involving appeals of grant reviewer decisions at the $3 billion California stem cell agency will be taken up once again April 26 by the directors' Science Subcommittee.
The agenda also includes possible action on a bank for reprogrammed stem cells.
No details are yet available on any of the proposals to be considered, but potential applicants for grants and loans would | | | | | | | | | | | | | | | | | | | | | | | | | Dental Implants and the Use of rhBMP-2. Oral Maxillofac Surg Clin North Am. 2011 May;23(2):347-361 Authors: Spagnoli DB, Marx RE Tissue engineering is an emerging field of medicine and dentistry that combines the body's natural biologic response to tissue injury with engineering principles. The goal is to replicate or reconstruct the natural form and function of missing tissues and organs. Tissue-engineered bone with native qualities will be necessary for implantation or migration of engineered teeth in the future, and is currently required for the osseointegration of dental implants. This article addresses the role of bone morphogenetic proteins (BMP) in native bone healing for implant osseointegration and the application of BMP for de novo bone regeneration. PMID: 21492806 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Ready for practice? A study of confidence levels of final year dental students at Cardiff University and University College Cork. Eur J Dent Educ. 2011 May;15(2):98-103 Authors: Honey J, Lynch CD, Burke FM, Gilmour AS Aim: The aim of this study was to describe the self-reported confidence levels of final year students at the School of Dentistry, Cardiff University and at the University Dental School & Hospital, Cork, Ireland in performing a variety of dental procedures commonly completed in primary dental care settings. Method: A questionnaire was distributed to 61 final year students at Cardiff and 34 final year students at Cork. Information requested related to the respondents confidence in performing a variety of routine clinical tasks, using a five-point scale (1 = very little confidence, 5 = very confident). Comparisons were made between the two schools, gender of the respondent, and whether or not a student intended completing a year of vocational training after graduation. Results: A response rate of 74% was achieved (n = 70). The greatest self-reported confidence scores were for 'scale and polish' (4.61), fissure sealants (4.54) and delivery of oral hygiene instruction (4.51). Areas with the least confidence were placement of stainless steel crowns (2.83), vital tooth bleaching (2.39) and surgical extractions (2.26). Students at Cardiff were more confident than those at Cork in performing simple extractions (Cardiff: 4.31; Cork: 3.76) and surgical extractions (Cardiff: 2.61; Cork: 1.88), whilst students in Cork were more confident in caries diagnosis (Cork: 4.24; Cardiff: 3.89) fissure sealing (Cork: 4.76; Cardiff: 4.33) and placement of preventive resin restorations (Cork: 4.68; Cardiff: 4.22). Conclusion: Final year students at Cardiff and Cork were most confident in simpler procedures and procedures in which they had had most clinical experience. They were least confident in more complex procedures and procedures in which they had the least clinical experience. Increased clinical time in complex procedures may help in increasing final year students' confidence in those areas. PMID: 21492345 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The Multi-parametric Effects of Hydrodynamic Environments on Stem Cell Culture. Tissue Eng Part B Rev. 2011 Apr 14; Authors: Kinney MA, Sargent CY, McDevitt TC Stem cells possess the unique capacity to differentiate into many clinically relevant somatic cell types, making them a promising cell source for tissue engineering applications and regenerative medicine therapies. However, in order for the therapeutic promise of stem cells to be fully realized, scalable approaches to efficiently direct differentiation must be developed. Traditionally, suspension culture systems are employed for the scale-up manufacturing of biologics via bioprocessing systems that heavily rely upon various types of bioreactors. However, in contrast to conventional bench-scale static cultures, large-scale suspension cultures impart complex hydrodynamic forces on cells and aggregates due to fluid mixing conditions. Stem cells are exquisitely sensitive to environmental perturbations, thus motivating the need for a more systematic understanding of the effects of hydrodynamic environments on stem cell expansion and differentiation. This article focuses on the inter-dependent relationships between stem cell aggregation, metabolism, and phenotype in the context of hydrodynamic culture environments. Ultimately, an improved understanding of the multi-factorial response of stem cells to mixed culture conditions will enable the design of bioreactors and bioprocessing systems for scalable directed differentiation approaches. PMID: 21491967 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Construction of A Fluorescent Nanostructured Chitosan-hydroxyapatite Scaffold by Nano-crystallon Induced Biomimetic Mineralization and its cell Biocompatibility. ACS Appl Mater Interfaces. 2011 Apr 14; Authors: Wang G, Zheng L, Zhao H, Miao J, Sun C, Liu H, Huang Z, Yu X, Wang J, Tao X Biomaterial surfaces and their nanostructures can significantly influence cell growth and viability. Thus, manipulating surface characteristics of scaffolds can be a potential strategy to control cell functions for stem cell tissue engineering. In this study, in order to construct a hydroxyapatite (HAp) coated genipin-chitosan conjugation scaffold (HGCCS) with a well-defined HAp nanostructured surface, we have developed a simple and controllable approach that allows construction of a 2-level 3-dimensional (3D) networked structure to provide sufficient calcium source and achieve desired mechanical function and mass transport (permeability and diffusion) properties. Using a nontoxic cross-linker (genipin) and a nano-crystallon induced biomimetic mineralization method, we first assembled a layer of HAp network-like nanostructure on a 3D porous chitosan-based framework. X-ray diffraction (XRD) and high resolution transmission electron microscopy (HRTEM) analysis confirm that the continuous network-like nanostructure on the channel surface of the HGCCS is composed of crystalline HAp. Compressive testing demonstrated that the strength of the HGCCS is apparently enhanced because of the strong cross-linking of genipin and the resulting reinforcement of the HAp nano-network. The fluorescence properties of genipin-chitosan conjugation for convenient monitoring of the 3D porous scaffold biodegradability and cell localization in the scaffold was specifically explored using confocal laser scanning microscopy (CLSM). Furthermore, through scanning electron microscope (SEM) observation and immunofluorescence measurements of F-actin, we found that the HAp network-like nanostructure on the surface of the HGCCS can influence the morphology and integrin-mediated cytoskeleton organization of rat bone marrow-derived mesenchymal stem cells (BMSCs). Based on cell proliferation assays, rat BMSCs tend to have higher viability on HGCCS in vitro. The results of this study suggest that the fluorescent 2-level 3D nanostructured chitosan-HAp scaffold will be a promising scaffold for bone tissue engineering application. PMID: 21491931 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Biaxial biomechanical properties of self-assembly tissue-engineered blood vessels. J R Soc Interface. 2011 Feb 6;8(55):244-56 Authors: Zaucha MT, Gauvin R, Auger FA, Germain L, Gleason RL Along with insights into the potential for graft success, knowledge of biomechanical properties of small diameter tissue-engineered blood vessel (TEBV) will enable designers to tailor the vessels' mechanical response to closer resemble that of native tissue. Composed of two layers that closely mimic the native media and adventitia, a tissue-engineered vascular adventitia (TEVA) is wrapped around a tissue-engineered vascular media (TEVM) to produce a self-assembled tissue-engineered media/adventia (TEVMA). The current study was undertaken to characterize the biaxial biomechanical properties of TEVM, TEVA and TEVMA under physiological pressures as well as characterize the stress-free reference configuration. It was shown that the TEVA had the greatest compliance over the physiological loading range while the TEVM had the lowest compliance. As expected, compliance of the SA-TEBV fell in between with an average compliance of 2.73 MPa(-1). Data were used to identify material parameters for a microstructurally motivated constitutive model. Identified material parameters for the TEVA and TEVM provided a good fit to experimental data with an average coefficient of determination of 0.918 and 0.868, respectively. These material parameters were used to develop a two-layer predictive model for the response of a TEVMA which fit well with experimental data. PMID: 20554564 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Chondrogenic Priming Adipose-Mesenchymal Stem Cells for Cartilage Tissue Regeneration. Pharm Res. 2011 Apr 15; Authors: Hwang NS, Im SG, Wu PB, Bichara DA, Zhao X, Randolph MA, Langer R, Anderson DG PURPOSE: Chondrocytes lose their ability to produce cartilaginous matrix during multiplication in culture through repeated passages, resulting in inferior tissue phenotype. To overcome the limited amount of primary chondrocytes, we aimed to determine the optimal culture condition for in vitro/in vivo cartilage regeneration using human adipose-derived mesenchymal stem cells (AMSCs). METHODS: To evaluate the effects exerted by the chondrocytic culture condition on AMSC, we utilized chondrocyte conditioned medium (CM) and/or co-culture methods to prime and differentiate AMSCs. We evaluated ultimate in vivo engineered cartilage with primed AMSCs with that of chondrocytes. To examine the link between conditioned factors and proliferation/differentiation, cell cycle progression of AMSCs were examined using 5-ethynyl-2'-deoxyuridine (EdU), and gene expression was monitored. RESULTS: We report that AMSCs can be stimulated to become chondrogenic cells when expanded with chondrocyte CM. Polymeric scaffolds co-seeded with CM- expanded AMSCs and primary chondrocytes resulted in in vivo cartilaginous tissues with similar biochemical content to constructs seeded with chondrocytes alone. CONCLUSION: These results indicate that chondrocyte CM consists of suitable morphogenetic factors that induce the chondrogenic priming of AMSCs for cartilage tissue engineering. PMID: 21494923 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Human Galectins Induce Conversion of Dermal Fibroblasts into Myofibroblasts and Production of Extracellular Matrix: Potential Application in Tissue Engineering and Wound Repair. Cells Tissues Organs. 2011 Apr 14; Authors: Dvořánková B, Szabo P, Lacina L, Gal P, Uhrova J, Zima T, Kaltner H, André S, Gabius HJ, Sykova E, Smetana K Members of the galectin family of endogenous lectins are potent adhesion/growth-regulatory effectors. Their multifunctionality opens possibilities for their use in bioapplications. We studied whether human galectins induce the conversion of human dermal fibroblasts into myofibroblasts (MFBs) and the production of a bioactive extracellular matrix scaffold is suitable for cell culture. Testing a panel of galectins of all three subgroups, including natural and engineered variants, we detected activity for the proto-type galectin-1 and galectin-7, the chimera-type galectin-3 and the tandem-repeat-type galectin-4. The activity of galectin-1 required the integrity of the carbohydrate recognition domain. It was independent of the presence of TGF-β1, but it yielded an additive effect. The resulting MFBs, relevant, for example, for tumor progression, generated a matrix scaffold rich in fibronectin and galectin-1 that supported keratinocyte culture without feeder cells. Of note, keratinocytes cultured on this substratum presented a stem-like cell phenotype with small size and keratin-19 expression. In vivo in rats, galectin-1 had a positive effect on skin wound closure 21 days after surgery. In conclusion, we describe the differential potential of certain human galectins to induce the conversion of dermal fibroblasts into MFBs and the generation of a bioactive cell culture substratum. PMID: 21494018 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Preface Toward Tissue Engineering in Maxillofacial Reconstruction. Oral Maxillofac Surg Clin North Am. 2011 May;23(2):ix Authors: Jensen OT PMID: 21492794 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Melt electrospinning. Chem Asian J. 2011 Jan 3;6(1):44-56 Authors: Hutmacher DW, Dalton PD Melt electrospinning is relatively under-investigated compared to solution electrospinning but provides opportunities in numerous areas, in which solvent accumulation or toxicity are a concern. These applications are diverse, and provide a broad set of challenges to researchers involved in electrospinning. In this context, melt electrospinning provides an alternative approach that bypasses some challenges to solution electrospinning, while bringing new issues to the forefront, such as the thermal stability of polymers. This Focus Review describes the literature on melt electrospinning, as well as highlighting areas where both melt and solution are combined, and potentially merge together in the future. PMID: 21080400 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Delayed Administration of Human Umbilical Tissue-Derived Cells Improved Neurological Functional Recovery in a Rodent Model of Focal Ischemia. Stroke. 2011 Apr 14; Authors: Zhang L, Li Y, Zhang C, Chopp M, Gosiewska A, Hong K BACKGROUND AND PURPOSE: The short time window required by neuroprotective strategies for successful treatment of patients with ischemic stroke precludes treatment for most. However, clinical therapies based on neuroregeneration might extend this therapeutic time window and thus address a significant unmet need. Human umbilical tissue-derived cells have shown great potential as neuroregenerative candidates for stroke treatment. METHODS: The effectiveness of intravenous administration of human umbilical tissue-derived cells was tested in a rodent middle cerebral artery stroke model in a dose escalation study (doses tested: 3×10(5), 1×10(6), 3×x10(6), or 1×10(7) cells/injection) followed by a time-of-administration study (time after stroke: Day 1, Day 7, Day 30, and Day 90 at a dose of 5×10(6) cells/injection). Controls were phosphate-buffered saline injections and human bone marrow-derived mesenchymal stromal cell injections. Post-treatment outcome tools included the modified neurological severity score and the adhesive removal tests. Histology was performed on all cases to evaluate synaptogenesis, neurogenesis, angiogenesis, and cell apoptosis. RESULTS: Statistically significant improvements of human umbilical tissue-derived cell treatment versus phosphate-buffered saline in modified neurological severity scores and adhesive test results were observed for doses ≥3×10(6) cells up to 30 days poststroke. At doses ≥3×10(6), histological evaluations confirmed enhanced synaptogenesis, vessel density, and reduced apoptosis in the ischemic boundary zone and increased proliferation of progenitor cells in the subventricular zone of human umbilical tissue-derived cell-treated animals versus phosphate-buffered saline controls. CONCLUSIONS: These results indicate effectiveness of intravenous administration of human umbilical tissue-derived cells in a rodent stroke model compared with phosphate-buffered saline control and warrant further investigation for possible use in humans. PMID: 21493915 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A Universal System for Highly Efficient Cardiac Differentiation of Human Induced Pluripotent Stem Cells That Eliminates Interline Variability. PLoS One. 2011;6(4):e18293 Authors: Burridge PW, Thompson S, Millrod MA, Weinberg S, Yuan X, Peters A, Mahairaki V, Koliatsos VE, Tung L, Zambidis ET BACKGROUND: The production of cardiomyocytes from human induced pluripotent stem cells (hiPSC) holds great promise for patient-specific cardiotoxicity drug testing, disease modeling, and cardiac regeneration. However, existing protocols for the differentiation of hiPSC to the cardiac lineage are inefficient and highly variable. We describe a highly efficient system for differentiation of human embryonic stem cells (hESC) and hiPSC to the cardiac lineage. This system eliminated the variability in cardiac differentiation capacity of a variety of human pluripotent stem cells (hPSC), including hiPSC generated from CD34(+) cord blood using non-viral, non-integrating methods. METHODOLOGY/PRINCIPAL FINDINGS: We systematically and rigorously optimized >45 experimental variables to develop a universal cardiac differentiation system that produced contracting human embryoid bodies (hEB) with an improved efficiency of 94.7±2.4% in an accelerated nine days from four hESC and seven hiPSC lines tested, including hiPSC derived from neonatal CD34(+) cord blood and adult fibroblasts using non-integrating episomal plasmids. This cost-effective differentiation method employed forced aggregation hEB formation in a chemically defined medium, along with staged exposure to physiological (5%) oxygen, and optimized concentrations of mesodermal morphogens BMP4 and FGF2, polyvinyl alcohol, serum, and insulin. The contracting hEB derived using these methods were composed of high percentages (64-89%) of cardiac troponin I(+) cells that displayed ultrastructural properties of functional cardiomyocytes and uniform electrophysiological profiles responsive to cardioactive drugs. CONCLUSION/SIGNIFICANCE: This efficient and cost-effective universal system for cardiac differentiation of hiPSC allows a potentially unlimited production of functional cardiomyocytes suitable for application to hPSC-based drug development, cardiac disease modeling, and the future generation of clinically-safe nonviral human cardiac cells for regenerative medicine. PMID: 21494607 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Substantial expression of mature elastin in arterial constructs. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2705-10 Authors: Lee KW, Stolz DB, Wang Y Mature elastin synthesis is a key challenge in arterial tissue engineering. Most engineered vessels lack elastic fibers in the medial layer and those present are poorly organized. The objective of this study is to increase mature elastin synthesis in small-diameter arterial constructs. Adult primary baboon smooth muscle cells (SMCs) were seeded in the lumen of porous tubular scaffolds fabricated from a biodegradable elastomer, poly(glycerol sebacate) (PGS) and cultured in a pulsatile flow bioreactor for 3 wk. We tested the effect of pore sizes on construct properties by histological, biochemical, and mechanical evaluations. Histological analysis revealed circumferentially organized extracellular matrix proteins including elastin and the presence of multilayered SMCs expressing calponin and α-smooth muscle actin. Biochemical analysis demonstrated that the constructs contained mature elastin equivalent to 19% of the native arteries. Mechanical tests indicated that the constructs could withstand up to 200 mmHg burst pressure and exhibited compliance comparable to native arteries. These results show that nontransfected cells in PGS scaffolds in unsupplemented medium produced a substantial amount of mature elastin within 3 wk and the elastic fibers had similar orientation as those in native arteries. The 25-32 μm pore size supported cell organization and elastin synthesis more than larger pore sizes. To our knowledge, there was no prior report of the synthesis of mature and organized elastin in arterial constructs without exogenous factors or viral transduction. PMID: 21282618 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The promotion of axon extension in vitro using polymer-templated fibrin scaffolds. Biomaterials. 2011 Apr 12; Authors: Scott JB, Afshari M, Kotek R, Saul JM Biomaterial nerve cuffs are a clinical alternative to autografts and allografts as a means to repair segmental peripheral nerve defects. However, existing clinical biomaterial constructs lack true incorporation of physical guidance cues into their design. In both two- and three-dimensional systems, it is known that substrate geometry directly affects rates of axon migration. However, the ability to incorporate these cues into biomaterial scaffolds of sufficient porosity to promote robust nerve regeneration in three-dimensional systems is a challenge. We have developed fibrin constructs fabricated by a sacrificial templating approach, yielding scaffolds with multiple 10-250 μm diameter conduits depending on the diameter of the template fibers. The resulting scaffolds contained numerous, highly aligned conduits, had porosity of ∼ 80%, and showed mechanical properties comparable to native nerve (150-300 kPa Young's modulus). We studied the effects of the conduit diameters on the rate of axon migration through the scaffold to investigate if manipulation of this geometry could be used to ultimately promote more rapid bridging of the scaffold. All diameters studied led to axon migration, but in contrast to effects of fiber diameters in other systems, the rate of axon migration was independent of conduit diameter in these templated scaffolds. However, aligned conduits did support more rapid axon migration than non-aligned, tortuous controls. PMID: 21492932 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The Multi-parametric Effects of Hydrodynamic Environments on Stem Cell Culture. Tissue Eng Part B Rev. 2011 Apr 14; Authors: Kinney MA, Sargent CY, McDevitt TC Stem cells possess the unique capacity to differentiate into many clinically relevant somatic cell types, making them a promising cell source for tissue engineering applications and regenerative medicine therapies. However, in order for the therapeutic promise of stem cells to be fully realized, scalable approaches to efficiently direct differentiation must be developed. Traditionally, suspension culture systems are employed for the scale-up manufacturing of biologics via bioprocessing systems that heavily rely upon various types of bioreactors. However, in contrast to conventional bench-scale static cultures, large-scale suspension cultures impart complex hydrodynamic forces on cells and aggregates due to fluid mixing conditions. Stem cells are exquisitely sensitive to environmental perturbations, thus motivating the need for a more systematic understanding of the effects of hydrodynamic environments on stem cell expansion and differentiation. This article focuses on the inter-dependent relationships between stem cell aggregation, metabolism, and phenotype in the context of hydrodynamic culture environments. Ultimately, an improved understanding of the multi-factorial response of stem cells to mixed culture conditions will enable the design of bioreactors and bioprocessing systems for scalable directed differentiation approaches. PMID: 21491967 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Labeling of mesenchymal stromal cells with iron oxide-poly(l-lactide) nanoparticles for magnetic resonance imaging: uptake, persistence, effects on cellular function and magnetic resonance imaging properties. Cytotherapy. 2011 Apr 15; Authors: Schmidtke-Schrezenmeier G, Urban M, Musyanovych A, Mailänder V, Rojewski M, Fekete N, Menard C, Deak E, Tarte K, Rasche V, Landfester K, Schrezenmeier H Abstract Background aims. Mesenchymal stromal cells (MSC) are the focus of research in regenerative medicine aiming at the regulatory approval of these cells for specific indications. To cope with the regulatory requirements for somatic cell therapy, novel approaches that do not interfere with the natural behavior of the cells are necessary. In this context in vivo magnetic resonance imaging (MRI) of labeled MSC could be an appropriate tool. Cell labeling for MRI with a variety of different iron oxide preparations is frequently published. However, most publications lack a comprehensive assessment of the non-interference of the contrast agent with the functionality of the labeled MSC, which is a prerequisite for the validity of cell-tracking via MRI. Methods. We studied the effects of iron oxide-poly(l-lactide) nanoparticles in MSC with flow cytometry, transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), Prussian blue staining, CyQuant® proliferation testing, colony-forming unit-fibroblast (CFU-F) assays, flow chamber adhesion testing, immunologic tests and differentiation tests. Furthermore iron-labeled MSC were studied by MRI in agarose phantoms and Wistar rats. Results. It could be demonstrated that MSC show rapid uptake of nanoparticles and long-lasting intracellular persistence in the endosomal compartment. Labeling of the MSC with these particles has no influence on viability, differentiation, clonogenicity, proliferation, adhesion, phenotype and immunosuppressive properties. They show excellent MRI properties in agarose phantoms and after subcutaneous implantation in rats over several weeks. Conclusions. These particles qualify for studying MSC homing and trafficking via MRI. PMID: 21492060 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | <em>In Vivo</em> Canine Muscle Function Assay. J Vis Exp. 2011;(50) Authors: Childers MK, Grange RW, Kornegay JN We describe a minimally-invasive and reproducible method to measure canine pelvic limb muscle strength and muscle response to repeated eccentric contractions. The pelvic limb of an anesthetized dog is immobilized in a stereotactic frame to align the tibia at a right angle to the femur. Adhesive wrap affixes the paw to a pedal mounted on the shaft of a servomotor to measure torque. Percutaneous nerve stimulation activates pelvic limb muscles of the paw to either push (extend) or pull (flex) against the pedal to generate isometric torque. Percutaneous tibial nerve stimulation activates tibiotarsal extensor muscles. Repeated eccentric (lengthening) contractions are induced in the tibiotarsal flexor muscles by percutaneous peroneal nerve stimulation. The eccentric protocol consists of an initial isometric contraction followed by a forced stretch imposed by the servomotor. The rotation effectively lengthens the muscle while it contracts, e.g., an eccentric contraction. During stimulation flexor muscles are subjected to an 800 msec isometric and 200 msec eccentric contraction. This procedure is repeated every 5 sec. To avoid fatigue, 4 min rest follows every 10 contractions with a total of 30 contractions performed. PMID: 21494224 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Ultra-high-field MRI real-time imaging of HSC engraftment of the bone marrow niche. Leukemia. 2011 Apr 15; Authors: Bengtsson NE, Kim S, Lin L, Walter GA, Scott EW The bone marrow (BM) undergoes extensive remodeling following irradiation damage. A crucial part of restoring homeostasis following irradiation is the ability of hematopoietic stem cells (HSCs) to home to and engraft specialized niches within the BM through a remodeling BM vascular system. Here we show that a combination of ultra-high-field strength magnetic resonance imaging (17.6 T, MRI) coupled with fluorescent microscopy (FLM) serves as a powerful tool for the in vivo imaging of cell homing within the BM. Ultra-high-field MRI can achieve high-resolution three-dimensional (3D) images (28 × 28 × 60 μm(3)) of the BM in live mice, sufficient to resolve anatomical changes in BM microstructures attributed to radiation damage. Following intra-arterial infusion with dsRed-expressing BM cells, labeled with superparamagnetic iron oxides, both FLM and MRI could be used to follow initial homing and engraftment of donor HSC to a limited number of preferred sites within a few cell diameters of the calcified bone-the endosteal niche. Subsequent histology confirmed the fidelity and accuracy of MRI to create non-invasive, high-resolution 3D images of donor cell engraftment of the BM in living animals at the level of single-cell detection.Leukemia advance online publication, 15 April 2011; doi:10.1038/leu.2011.72. PMID: 21494252 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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