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Articles by Kang Ting in JoVE
JoVE Bioengineering
Användning av mänskliga perivaskulär stamceller för benuppbyggnad
1Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA, 2UCLA and Orthopaedic Hospital, Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, UCLA, 3Department of Bioengineering, UCLA, 4Center for Cardiovascular Science, University of Edinburgh
Mänskliga perivaskulära stamceller (PSC) är en ny stamcell klass för skelett vävnadsregenerering liknar mesenkymala stamceller (MSC). PSC kan isoleras genom FACS (fluorescensaktiverad cellsortering) från fettvävnad anskaffas under normal fettsugning förfaranden, kombinerades sedan med ett osteoinduktivt byggnadsställning för att uppnå benbildning
Other articles by Kang Ting on PubMed
Confocal Laser Scanning Microscopic Analysis of Collagen Scaffolding Patterns in Cranial Sutures
Although recent studies indicate that regional dura mater influences the fate of the overlying cranial suture, little is known about the assembly of extracellular matrix (ECM) molecules within the patent and fusing murine cranial suture complexes. Confocal laser scanning microscopy was used to study ECM assembly within patent and fusing cranial suture complexes. Coronal sections (20 microm thick) of patent sagittal (SAG) and fusing posterior frontal (PF) sutures from postnatal 8-, 14-, and 18-day-old Sprague-Dawley rats were scanned in 0.5-microm increments, and images were collected consecutively to create a z-series for three-dimensional reconstruction. Spatial and temporal collagen arrangements were compared between SAG and PF sutures by measuring interfiber distance, fiber thickness, and total collagen surface area at each time point. We demonstrate that on day 8 (before the onset of suture fusion), collagen bundles are randomly arranged in both the SAG and PF sutures. By day 14 (midfusion period), there was a statistically significant reduction in total collagen surface area (80.5% versus 67.4%; P < 0.05) as the collagen bundles were organized into orthogonal lattices along the anterior and endocranial margins of the PF suture. Furthermore, new bone matrix deposition was observed along the edges of these organized collagen bundles. In contrast, collagen within the SAG suture remained randomly arranged and unossified. By day 18 (late fusion period), the PF suture was completely fused except for the posterior-ectocranial portion. This patent section of the PF suture contained a highly organized mineralizing orthogonal collagen lattice. The total collagen surface area in the day-18 PF suture continued to decline compared with the day-8 PF suture (80.5% versus 55.6%; P < 0.05). In the day-18 SAG suture, the collagen bundles remained randomly arranged, and the total surface area did not change. The same analysis was performed in a human pathologic fusing and patent suture. Similar results were observed. The total collagen surface area significantly decreased in the pathologic fusing human suture compared with the patent suture (92.8% versus 60.6%; P < 0.05). Moreover, the pathologically fusing suture contained a highly organized mineralizing orthogonal collagen lattice. This is the first analysis of collagen patterns in patent and fusing cranial sutures.
Preparation and Characterization of Trace Elements-multidoped Injectable Biomimetic Materials for Minimally Invasive Treatment of Osteoporotic Bone Trauma
It has always been a clinical challenge to use the proper implants or biomaterials to restore function to traumatized bone defects in patients with osteoporosis. In this study, we prepared the alginate-chitosan/trace elements-multidoped octacalcium phosphate-bioglass (AT-CS/teOCP-BG) hydrogel composite as an injectable biomaterial and evaluated its physicochemical properties and biological performance. Trace amount of silicon, strontium, and zinc was first doped into the structure of OCP porous microspheres via a wet chemical reaction. The AT-CS complex was mechanically mixed with teOCP and then neutralized by the ionic products of bioglass 58S particles dissolution. Formulations of this novel composite presented in wet state have teOCP-BG contents ranging from 7.8 to 25.4% and AT-CS content of below 3.2%. The composite retained gel in culture medium at 37°C, and the ratio of storage modulus and loss modulus (G'/G″) exhibited a marked increase with decreasing the amount of BG, signifying a pH-dependent enhancement of rheological properties and gel stability. After injection into rat femoral bone marrow cavity with minimal tissue invasion, new bone ingrowth was observed from radiologic images in the ovariectomized (OVXed) rats, which was significantly greater than that found in sham-operated animals within 8 weeks postoperatively. The fast bone regeneration phenomenon was observed in the OVXed rats by radiographic and microcomputerized tomography examination and histological analysis. These findings suggest that the AT-CS/teOCP-BG system might be used as an injectable biomaterial for minimally invasive treatment of osteoporosis-related (micro-)trauma.
NELL1 Promotes High-quality Bone Regeneration in Rat Femoral Distraction Osteogenesis Model
NELL1 (NEL-like molecule-1; NEL [a protein strongly expressed in neural tissue encoding epidermal growth factor like domain]) is a cranisynostosis-associated molecule directly regulated by Runx2, the master molecule in controlling osteoblastic differentiation. NELL1 has exhibited potent osteoinductive activity for bone regeneration in several animal models. However, its capacity for promoting repair of long-bone defects remains unknown. In this study, we investigated the osteogenic effects of NELL1 on femoral distraction osteogenesis using adenoviral gene delivery and multiple approaches of in vivo analysis. Thirty Sprague-Dawley (SD) rats were randomly assigned to 3 groups for treatment (n=10 each): adenovirus-green fluorescent protein (Ad-GFP)-NELL1 or Ad-GFP at 1×10⁹ plaque-forming units/ml diluted in saline, or saline alone. The femoral distraction was at a speed of 0.25 mm every 12h for 14 days, and a single injection of Ad-GFP-NELL1 or Ad-GFP was given at the mid-distraction period. The effective NELL1 delivery in vivo after Ad-GFP-NELL1 injection was evaluated by optical imaging. The bone regeneration was assessed quantitatively at days 21, 28, 42, and 56 by live 3-D micro-computed tomography (micro-CT), and animals were sacrificed at day 56 for biomechanical testing and histological analysis. Exogenous NELL1 was expressed in the distracted gap for at least 14 days after Ad-GFP-NELL1 transfection. The bone union rate in the distracted gap was significantly higher with Ad-GFP-NELL1 than with Ad-GFP (9/9 vs. 4/9 rats) or saline alone (5/9 rats) at day 56. The serial 3-D micro-CT images and quantitation obtained with the development and application of radiolucent external fixators showed less callus but more mature cortical bones formed with Ad-GFP-NELL1 than with Ad-GFP transfection and saline administration during distraction osteogenesis. The biomechanical properties of femur samples with Ad-GFP-NELL1 transfection were better than samples with Ad-GFP transfection or saline treatment, and were similar with unoperated femurs. Histology revealed cartilaginous tissues in the middle of distraction gaps with Ad-GFP transfection and saline treatment but only bony bridges with Ad-GFP-NELL1 transfection at the final time point (day 56). Coincidently, the expression of Runx2, BMP2, and BMP7 did not differ among groups at day 56, whereas the expression of osteocalcin and osteopontin was slightly higher with Ad-GFP-NELL1 transfection. Thus, sustained Ad-NELL1 protein delivery into a local area of a rat femoral distraction osteogenesis model remarkably improved regeneration of good-quality bones and accelerated bone union at a high rate. Acquiring serial micro-CT data during rat femoral distraction osteogenesis and regional adenovirus delivery of NELL1 may facilitate future in vivo studies.
Therapeutic Effects of Neuregulin-1 in Diabetic Cardiomyopathy Rats
Diabetic cardiomyopathy (DCM) is a disorder of the heart muscle in people with diabetes, which is characterized by both systolic and diastolic dysfunction. The effective treatment strategy for DCM has not been developed.
Additive Effects of Sonic Hedgehog and Nell-1 Signaling in Osteogenic Versus Adipogenic Differentiation of Human Adipose-Derived Stromal Cells
A theoretical inverse relationship exists between osteogenic (bone forming) and adipogenic (fat forming) mesenchymal stem cell (MSC) differentiation. This inverse relationship in theory partially underlies the clinical entity of osteoporosis, in which marrow MSCs have a preference for adipose differentiation that increases with age. Two pro-osteogenic cytokines have been recently studied that each also possesses antiadipogenic properties: Sonic Hedgehog (SHH) and NELL-1 proteins. In the present study, we assayed the potential additive effects of the biologically active N-terminus of SHH (SHH-N) and NELL-1 protein on osteogenic and adipogenic differentiation of human primary adipose-derived stromal cell (hASCs). We observed that both recombinant SHH-N and NELL-1 protein significantly enhanced osteogenic differentiation and reduced adipose differentiation across all markers examined (alkaline phosphatase, Alizarin red and Oil red O staining, and osteogenic gene expression). Moreover, SHH-N and NELL-1 directed signaling produced additive effects on the pro-osteogenic and antiadipogenic differentiation of hASCs. NELL-1 treatment increased Hedgehog signaling pathway expression; coapplication of the Smoothened antagonist Cyclopamine reversed the pro-osteogenic effect of NELL-1. In summary, Hedgehog and Nell-1 signaling exert additive effects on the pro-osteogenic and antiadipogenic differentiation of ASCs. These studies suggest that the combination cytokines SHH-N+NELL-1 may represent a viable future technique for inducing the osteogenic differentiation of MSCs.
Calvarial Cleidocraniodysplasia-Like Defects With ENU-Induced Nell-1 Deficiency
ABSTRACT: Nell-1, first identified by its overexpression in synostotic cranial sutures, is a novel osteoinductive growth and differentiation factor. To further define Nell-1's role in craniofacial patterning, we characterized defects of the ENU-induced Nell-1-deficient (END) mice, focusing on both intramembranous and endochondral cranial bones. Results showed that calvarial bones of neonatal END mice were reduced in thickness and density, with a phenotype resembling calvarial cleidocraniodysplasia. In addition, a global reduction in osteoblast markers was observed, including reductions in Runx2, alkaline phosphatase, and osteocalcin. Remarkably, detailed analysis of endochondral bones showed dysplasia as well. The chondrocranium in the END mouse showed enrichment for early, proliferating Sox9 chondrocytes, whereas in contrast markers of chondrocytes maturation were reduced. These data suggest that Nell-1 is an important growth factor for regulation of osteochondral differentiation, by regulating both Runx2 and Sox9 expression within the calvarium. In summary, Nell-1 is required for normal craniofacial membranous and endochondral skeletal development.
