cellular spheroids


Summary: Spherical, heterogeneous aggregates of proliferating, quiescent, and necrotic cells in culture that retain three-dimensional architecture and tissue-specific functions. The ability to form spheroids is a characteristic trait of CULTURED TUMOR CELLS derived from solid TUMORS. Cells from normal tissues can also form spheroids. They represent an in-vitro model for studies of the biology of both normal and malignant cells. (From Bjerkvig, Spheroid Culture in Cancer Research, 1992, p4)

Top Publications

  1. Barraud P, He X, Zhao C, Ibanez C, Raha Chowdhury R, Caldwell M, et al. Contrasting effects of basic fibroblast growth factor and epidermal growth factor on mouse neonatal olfactory mucosa cells. Eur J Neurosci. 2007;26:3345-57 pubmed
    ..In contrast, EGF appears to be primarily a survival factor for both the olfactory stem and precursor cells...
  2. Harper L, Piper K, Common J, Fortune F, Mackenzie I. Stem cell patterns in cell lines derived from head and neck squamous cell carcinoma. J Oral Pathol Med. 2007;36:594-603 pubmed
  3. de Witt Hamer P, Van Tilborg A, Eijk P, Sminia P, Troost D, Van Noorden C, et al. The genomic profile of human malignant glioma is altered early in primary cell culture and preserved in spheroids. Oncogene. 2008;27:2091-6 pubmed
    ..This implies that glioma cell culture data have to be handled with the highest caution...
  4. Mani S, Guo W, Liao M, Eaton E, Ayyanan A, Zhou A, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704-15 pubmed publisher
    ..These findings illustrate a direct link between the EMT and the gain of epithelial stem cell properties...
  5. Todaro M, Alea M, Di Stefano A, Cammareri P, Vermeulen L, Iovino F, et al. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell. 2007;1:389-402 pubmed publisher
    ..Our data suggest that colon tumor growth is dictated by stem-like cells that are treatment resistant due to the autocrine production of IL-4...
  6. Friedrich J, Ebner R, Kunz Schughart L. Experimental anti-tumor therapy in 3-D: spheroids--old hat or new challenge?. Int J Radiat Biol. 2007;83:849-71 pubmed
    ..To give a state-of-the-art overview on the promise of three-dimensional (3-D) culture systems for anticancer drug development, with particular emphasis on multicellular tumor spheroids (MCTS)...
  7. Cristini V, Li X, Lowengrub J, Wise S. Nonlinear simulations of solid tumor growth using a mixture model: invasion and branching. J Math Biol. 2009;58:723-63 pubmed publisher
    ..Accordingly, we believe this model is capable of describing complex invasive patterns observed in experiments...
  8. Qvarnström O, Simonsson M, Eriksson V, Turesson I, Carlsson J. gammaH2AX and cleaved PARP-1 as apoptotic markers in irradiated breast cancer BT474 cellular spheroids. Int J Oncol. 2009;35:41-7 pubmed
    ..markers, we have evaluated immunostaining patterns of gammaH2AX and cleaved PARP-1 in paraffin-embedded cellular spheroids. Breast cancer BT474 cells were grown as cell spheroids to diameters of 700-800 microm...
  9. Macklin P, McDougall S, Anderson A, Chaplain M, Cristini V, Lowengrub J. Multiscale modelling and nonlinear simulation of vascular tumour growth. J Math Biol. 2009;58:765-98 pubmed publisher
    ..In particular, the newly developing vessels tend to encapsulate, rather than penetrate, the tumour and are thus less effective in delivering nutrients...

More Information


  1. Delsanto P, Condat C, Pugno N, Gliozzi A, Griffa M. A multilevel approach to cancer growth modeling. J Theor Biol. 2008;250:16-24 pubmed
    ..cell groups dynamics), their consistency may be used to validate both approaches. It may also be interesting to note that the proposed formalism fits well into a recently proposed conjecture of growth laws universality...
  2. Kumar H, Zhong X, Hoelz D, Rescorla F, Hickey R, Malkas L, et al. Three-dimensional neuroblastoma cell culture: proteomic analysis between monolayer and multicellular tumor spheroids. Pediatr Surg Int. 2008;24:1229-34 pubmed publisher
    ..e., monolayers and MCTS...
  3. Mimura T, Yamagami S, Yokoo S, Usui T, Amano S. Selective isolation of young cells from human corneal endothelium by the sphere-forming assay. Tissue Eng Part C Methods. 2010;16:803-12 pubmed publisher
    ..Thus, the sphere-forming assay may contribute to obtaining the young cells needed for regenerative medicine...
  4. Mori H, Ninomiya K, Kino oka M, Shofuda T, Islam M, Yamasaki M, et al. Effect of neurosphere size on the growth rate of human neural stem/progenitor cells. J Neurosci Res. 2006;84:1682-91 pubmed
    ..These results suggest that the three-dimensional architecture of NSPC aggregates would create a microenvironment that promotes the proliferation of human NSPCs...
  5. Yamagami S, Yokoo S, Mimura T, Takato T, Araie M, Amano S. Distribution of precursors in human corneal stromal cells and endothelial cells. Ophthalmology. 2007;114:433-9 pubmed
  6. Nagase T, Matsumoto D, Nagase M, Yoshimura K, Shigeura T, Inoue M, et al. Neurospheres from human adipose tissue transplanted into cultured mouse embryos can contribute to craniofacial morphogenesis: a preliminary report. J Craniofac Surg. 2007;18:49-53; discussion 60-1 pubmed
    ..Although preliminary, our results support an idea that ASC-derived neurospheres have properties of neural progenitors in vitro and in vivo...
  7. Phillips T, McBride W, Pajonk F. The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst. 2006;98:1777-85 pubmed
    ..Cancer-initiating cells can now be prospectively isolated from breast cancer cell lines and tumor samples and propagated as mammospheres in vitro under serum-free conditions...
  8. Smalley K, Lioni M, Herlyn M. Life isn't flat: taking cancer biology to the next dimension. In Vitro Cell Dev Biol Anim. 2006;42:242-7 pubmed
    ..It is likely that the adoption of these and other 3D models will allow us to more closely re-create the behavior of the tumor in vivo which may lead to identifying better anticancer drug candidates at an earlier stage of development...
  9. Amano S, Yamagami S, Mimura T, Uchida S, Yokoo S. Corneal stromal and endothelial cell precursors. Cornea. 2006;25:S73-7 pubmed
    ..To isolate precursors of human corneal stromal and endothelial cells in vitro and to compare the distribution of rabbit corneal endothelial cell precursors in the central and peripheral regions of the cornea...
  10. Lan L, Cui D, Nowka K, Derwahl M. Stem cells derived from goiters in adults form spheres in response to intense growth stimulation and require thyrotropin for differentiation into thyrocytes. J Clin Endocrinol Metab. 2007;92:3681-8 pubmed
    ..This study aimed to analyze under which conditions quiescent stem cells derived from human goiters can be propagated to outgrow and whether these cells have retained the capacity to differentiate into thyroid cells...
  11. Ghods A, Irvin D, Liu G, Yuan X, Abdulkadir I, Tunici P, et al. Spheres isolated from 9L gliosarcoma rat cell line possess chemoresistant and aggressive cancer stem-like cells. Stem Cells. 2007;25:1645-53 pubmed
    ..Disclosure of potential conflicts of interest is found at the end of this article...
  12. Kang H, Jenabi J, Zhang J, Keshelava N, Shimada H, May W, et al. E-cadherin cell-cell adhesion in ewing tumor cells mediates suppression of anoikis through activation of the ErbB4 tyrosine kinase. Cancer Res. 2007;67:3094-105 pubmed
  13. Oktem G, Bilir A, Selvi N, Yurtseven M, Vatansever S, Ates U, et al. Chemotherapy influences inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) activity on 3D breast cancer cell line. Oncol Res. 2006;16:195-203 pubmed
    ..Therefore, analyzing the expression of both iNOS and eNOS might be very useful for targeting the treatment of breast carcinoma and obtaining better information on prognosis...
  14. Suzuki H, Bae Y. Evaluation of drug penetration with cationic micelles and their penetration mechanism using an in vitro tumor model. Biomaterials. 2016;98:120-30 pubmed publisher
    ..Our findings could be beneficial information to improve intratumoral penetration in new nanomedicines for solid tumors. ..
  15. Chen Y, Wang I, Young T. Formation of keratocyte spheroids on chitosan-coated surface can maintain keratocyte phenotypes. Tissue Eng Part A. 2009;15:2001-13 pubmed publisher
    ..However, such keratocyte spheroids do not proliferate and cannot withstand transforming growth factor-beta from myofibroblast differentiation. ..
  16. Piotrowska M, Angus S. A quantitative cellular automaton model of in vitro multicellular spheroid tumour growth. J Theor Biol. 2009;258:165-78 pubmed publisher
    ..Thus, the model suggests that an additional process is required to explain the experimentally observable onset of necrosis prior to the non-viable nutrient-deficient point being reached. ..
  17. Xiao Y, Ye Y, Yearsley K, Jones S, Barsky S. The lymphovascular embolus of inflammatory breast cancer expresses a stem cell-like phenotype. Am J Pathol. 2008;173:561-74 pubmed publisher
    ..This stem cell-like phenotype may contribute to the aggressive nature of IBC but also may lend itself to selective targeting. ..
  18. Siltanen C, Yaghoobi M, Haque A, You J, Lowen J, Soleimani M, et al. Microfluidic fabrication of bioactive microgels for rapid formation and enhanced differentiation of stem cell spheroids. Acta Biomater. 2016;34:125-132 pubmed publisher
    ..This approach also facilitated a ∼90-fold decrease in consumption of exogenous growth factors compared to conventional differentiation protocols. ..
  19. Fedotov S, Iomin A. Probabilistic approach to a proliferation and migration dichotomy in tumor cell invasion. Phys Rev E Stat Nonlin Soft Matter Phys. 2008;77:031911 pubmed
    ..The overall rate of tumor cell invasion for normal diffusion and subdiffusion is determined. ..
  20. Han M, Oba M, Nishiyama N, Kano M, Kizaka Kondoh S, Kataoka K. Enhanced percolation and gene expression in tumor hypoxia by PEGylated polyplex micelles. Mol Ther. 2009;17:1404-10 pubmed publisher
    ..To the best of our knowledge, our results demonstrated for the first time that polyplex micelles might show improved tumor penetrability over cationic polyplexes, thereby achieving transfection into the inside of the tumor tissue. ..
  21. Yang W, Yu H, Li G, Wei F, Wang Y, Liu L. Mask-free fabrication of a versatile microwell chip for multidimensional cellular analysis and drug screening. Lab Chip. 2017;17:4243-4252 pubmed publisher
  22. Prados J, Melguizo C, Rama A, Ortiz R, Segura A, Boulaiz H, et al. Gef gene therapy enhances the therapeutic efficacy of doxorubicin to combat growth of MCF-7 breast cancer cells. Cancer Chemother Pharmacol. 2010;66:69-78 pubmed publisher
    ..This therapeutic approach has the potential to overcome some of the major limitations of conventional chemotherapy, and may therefore constitute a promising strategy for future applications in breast cancer therapy. ..
  23. Liu H, Liu J, Qi C, Fang Y, Zhang L, Zhuo R, et al. Thermosensitive injectable in-situ forming carboxymethyl chitin hydrogel for three-dimensional cell culture. Acta Biomater. 2016;35:228-37 pubmed publisher
  24. Stahmann N, Woods A, Spengler K, Heslegrave A, Bauer R, Krause S, et al. Activation of AMP-activated protein kinase by vascular endothelial growth factor mediates endothelial angiogenesis independently of nitric-oxide synthase. J Biol Chem. 2010;285:10638-52 pubmed publisher
    ..In contrast, AMPKalpha2 was not involved in VEGF-triggered sprouting. The data suggest that AMPKalpha1 promotes VEGF-induced angiogenesis independently of eNOS, possibly by providing energy via inhibition of acetyl-CoA carboxylase. ..
  25. Reitan N, Juthajan A, Lindmo T, de Lange Davies C. Macromolecular diffusion in the extracellular matrix measured by fluorescence correlation spectroscopy. J Biomed Opt. 2008;13:054040 pubmed publisher
    ..This study demonstrates that one-photon FCS can be used to study the extracellular transport of macromolecules in tumor tissue, and that FCS provides additional information about diffusion properties compared to FRAP. ..
  26. Marian C, Wright W, Shay J. The effects of telomerase inhibition on prostate tumor-initiating cells. Int J Cancer. 2010;127:321-31 pubmed publisher
    ..These findings suggest that telomerase inhibition therapy may be able to efficiently target the prostate TICs in addition to the bulk tumor cells, providing new opportunities for combination therapies. ..
  27. Plachot C, Chaboub L, Adissu H, Wang L, Urazaev A, Sturgis J, et al. Factors necessary to produce basoapical polarity in human glandular epithelium formed in conventional and high-throughput three-dimensional culture: example of the breast epithelium. BMC Biol. 2009;7:77 pubmed publisher
    ..Although factors important for the establishment of basal polarity have been identified, requirements for the formation of apical polarity in three-dimensional tissue structures have not been thoroughly investigated...
  28. Jeong Y, Lee J, Shim J, Hur W. A scaffold-free surface culture of B16F10 murine melanoma cells based on magnetic levitation. Cytotechnology. 2016;68:2323-2334 pubmed
    ..0-3.7 in the 3D culture, due to an increased population of pigmented cells. This study presented a surface 3D culture of B16F10 cells without the use of a scaffold based on magnetic levitation. ..
  29. Lin R, Chu W, Chiang C, Lai C, Chang H. Magnetic reconstruction of three-dimensional tissues from multicellular spheroids. Tissue Eng Part C Methods. 2008;14:197-205 pubmed publisher
    ..These results indicate that magnetic organoid patterning is useful for construction of complex 3D tissue and will find applications in cell-to-cell interaction research, drug screening, and regenerative medicine. ..
  30. Kinasiewicz A, Gautier A, Lewiska D, Smietanka A, Legallais C, Werynski A. Three-dimensional growth of human hepatoma C3A cells within alginate beads for fluidized bioartificial liver. Int J Artif Organs. 2008;31:340-7 pubmed
    ..Alginate beads allow cultivation of cells in a 3-dimensional environment. The aim of our study was to assess the influence of a 3-dimensional culture in alginate microbeads, on hepatic cell metabolism...
  31. Haga T, Uchide N, Tugizov S, Palefsky J. Role of E-cadherin in the induction of apoptosis of HPV16-positive CaSki cervical cancer cells during multicellular tumor spheroid formation. Apoptosis. 2008;13:97-108 pubmed
  32. Luebke Wheeler J, Nedredal G, Yee L, Amiot B, Nyberg S. E-cadherin protects primary hepatocyte spheroids from cell death by a caspase-independent mechanism. Cell Transplant. 2009;18:1281-7 pubmed publisher
    ..In conclusion, E-cadherin is required for hepatocyte spheroid formation and may be responsible for protecting hepatocytes from a novel form of caspase-independent cell death. ..
  33. Nishikawa M, Yamamoto T, Kojima N, Kikuo K, Fujii T, Sakai Y. Stable immobilization of rat hepatocytes as hemispheroids onto collagen-conjugated poly-dimethylsiloxane (PDMS) surfaces: importance of direct oxygenation through PDMS for both formation and function. Biotechnol Bioeng. 2008;99:1472-81 pubmed
    ..These results show that appropriate surface modification of PDMS is a promising approach towards the development of liver tissue microdevices. ..
  34. Gaustad J, Brurberg K, Simonsen T, Mollatt C, Rofstad E. Tumor vascularity assessed by magnetic resonance imaging and intravital microscopy imaging. Neoplasia. 2008;10:354-62 pubmed
    ..F values colocalized with tumor regions showing high microvascular density and low BST values. Significant correlations were found between E.F and microvascular density and between E.F and BST, both within and among tumors. ..
  35. Kogashiwa Y, Sakurai H, Kimura T, Kohno N. Docetaxel suppresses invasiveness of head and neck cancer cells in vitro. Cancer Sci. 2010;101:1382-6 pubmed publisher
    ..In conclusion, Docetaxel treatment suppressed migration and invasiveness of head and neck cancer cells in vitro, which is likely to be mediated by regulating Cdc42 activity. ..
  36. Verseijden F, Posthumus van Sluijs S, Pavljasevic P, Hofer S, van Osch G, Farrell E. Adult human bone marrow- and adipose tissue-derived stromal cells support the formation of prevascular-like structures from endothelial cells in vitro. Tissue Eng Part A. 2010;16:101-14 pubmed publisher
    ..Further, our findings indicate that cell-cell contacts and reciprocal signaling play an important role in the formation of these prevascular structures. ..
  37. Goodman T, Chen J, Matveev K, Pun S. Spatio-temporal modeling of nanoparticle delivery to multicellular tumor spheroids. Biotechnol Bioeng. 2008;101:388-99 pubmed publisher
    ..The model was also used to investigate the effects of nanoparticle size. This model contributes toward the understanding of the role of tumor architecture on nanoparticle delivery efficiency. ..
  38. Herva M, Relaño Ginés A, Villa A, Torres J. Prion infection of differentiated neurospheres. J Neurosci Methods. 2010;188:270-5 pubmed publisher
    ..These results suggest that differentiated neurosphere cultures can complement prion bioassays in mouse models. ..
  39. Boyd M, Sorensen A, McCluskey A, Mairs R. Radiation quality-dependent bystander effects elicited by targeted radionuclides. J Pharm Pharmacol. 2008;60:951-8 pubmed publisher
    ..It is concluded that radiopharmaceutical-induced bystander effects may depend on LET of the decay particles but are independent of site of intracellular concentration of radionuclide. ..
  40. Marga F, Neagu A, Kosztin I, Forgacs G. Developmental biology and tissue engineering. Birth Defects Res C Embryo Today. 2007;81:320-8 pubmed publisher
    ..tissue fusion can be used both experimentally and theoretically to control and simulate the self-assembly of cellular spheroids into 3D living structures...
  41. Dubiak Szepietowska M, Karczmarczyk A, Jönsson Niedziółka M, Winckler T, Feller K. Development of complex-shaped liver multicellular spheroids as a human-based model for nanoparticle toxicity assessment in vitro. Toxicol Appl Pharmacol. 2016;294:78-85 pubmed publisher
    ..Therefore, this system can be applied to a wide variety of potentially hostile compounds in basic screening to provide initial warning of adverse effects and trigger subsequent analysis and remedial actions. ..
  42. Fang D, Kim Y, Lee C, Aggarwal S, McKinnon K, Mesmer D, et al. Expansion of CD133(+) colon cancer cultures retaining stem cell properties to enable cancer stem cell target discovery. Br J Cancer. 2010;102:1265-75 pubmed publisher
    ..Our data suggest that ex vivo-expanded colon CSCs isolated from clinical specimens can be maintained in culture enabling the identification of CSC cell surface-associated proteins. ..
  43. Rappa G, Mercapide J, Anzanello F, Prasmickaite L, Xi Y, Ju J, et al. Growth of cancer cell lines under stem cell-like conditions has the potential to unveil therapeutic targets. Exp Cell Res. 2008;314:2110-22 pubmed publisher
  44. Doyle K, Karl T, Hort Y, Duffy L, Shine J, Herzog H. Y1 receptors are critical for the proliferation of adult mouse precursor cells in the olfactory neuroepithelium. J Neurochem. 2008;105:641-52 pubmed
    ..Together these results indicate that NPY and the Y1 receptor are required for the normal proliferation of adult olfactory precursors and olfactory function. ..
  45. Tsai C, Chiang I, Wang J, Young T. Chitosan delaying human fibroblast senescence through downregulation of TGF-? signaling pathway. Artif Cells Nanomed Biotechnol. 2017;:1-12 pubmed publisher
    ..In summary, these results provide important information for considering the application of chitosan in the future cell therapy and regeneration medicine...
  46. Lee G, Lee J, Lee G, Joung W, Kim S, Lee S, et al. Networked concave microwell arrays for constructing 3-D cell spheroids. Biofabrication. 2017;: pubmed publisher
    ..Here we develop the novel networked concave microwell arrays for effective construction of 3-D multi-cellular spheroids. The proposed method provides a suitable structure for the diffusion of oxygen, water-soluble nutrients, and ..
  47. Sakai Y, Yoshida S, Yoshiura Y, Mori R, Tamura T, Yahiro K, et al. Effect of microwell chip structure on cell microsphere production of various animal cells. J Biosci Bioeng. 2010;110:223-9 pubmed publisher
    ..Thus, this chip technique is a promising cellular platform for tissue engineering or regenerative medicine research, pharmacological and toxicological studies, and fundamental studies in cell biology. ..
  48. Lee W, Pinckney J, Lee V, Lee J, Fischer K, Polio S, et al. Three-dimensional bioprinting of rat embryonic neural cells. Neuroreport. 2009;20:798-803 pubmed publisher
    ..The on-demand capability to print neural cells in a multilayered hydrogel scaffold offers flexibility in generating artificial 3D neural tissue composites. ..
  49. McMillan K, Boyd M, Zagnoni M. Transitioning from multi-phase to single-phase microfluidics for long-term culture and treatment of multicellular spheroids. Lab Chip. 2016;16:3548-57 pubmed publisher
    ..The work provides proof-of-concept results for using this system to test both chemo- and radio-therapeutic protocols using in vitro 3D cancer models. ..
  50. Jin Y, Wu Z, Li C, Zhou W, Shaw J, Baguley B, et al. Optimization of Weight Ratio for DSPE-PEG/TPGS Hybrid Micelles to Improve Drug Retention and Tumor Penetration. Pharm Res. 2018;35:13 pubmed publisher
    ..37-fold and 3.49-fold greater than that of free ASL. The optimized DSPE-PEG2000/TPGS micelles could serve as a promising vehicle to improve drug retention and penetration in tumor. ..
  51. Harm S, Stroble K, Hartmann J, Falkenhagen D. Alginate-encapsulated human hepatoma C3A cells for use in a bioartificial liver device - the hybrid-MDS. Int J Artif Organs. 2009;32:769-78 pubmed
    ..The microcapsules have to be permeable for essential proteins such as albumin...
  52. Kim J, Casaccia Bonnefil P. Interplay of hormones and p53 in modulating gender dimorphism of subventricular zone cell number. J Neurosci Res. 2009;87:3297-305 pubmed publisher
    ..Together with previous reports, these results implicate p53 as an important component of the mechanism regulating gender dimorphism in the SVZ...
  53. Lee J, Cuddihy M, Cater G, Kotov N. Engineering liver tissue spheroids with inverted colloidal crystal scaffolds. Biomaterials. 2009;30:4687-94 pubmed publisher
    ..Since the aggregation of cells into clusters is a universal biological process, these findings and scaffolds can be applied to many other relevant cell types...
  54. Siegwart D, Srinivasan A, Bencherif S, Karunanidhi A, Oh J, Vaidya S, et al. Cellular uptake of functional nanogels prepared by inverse miniemulsion ATRP with encapsulated proteins, carbohydrates, and gold nanoparticles. Biomacromolecules. 2009;10:2300-9 pubmed publisher
    ..Application of ATRP enabled the synthesis of a functionalized drug delivery system with a uniform network that is capable of encapsulating and delivering inorganic, organic, and biological molecules...
  55. Amoozegar C, Giacomelli M, Keener J, Chalut K, Wax A. Experimental verification of T-matrix-based inverse light scattering analysis for assessing structure of spheroids as models of cell nuclei. Appl Opt. 2009;48:D20-5 pubmed
    ..In comparison, analysis using the T-matrix method is highly accurate and more reliable yet requires measurements from only a single orientation...
  56. Verma P, Verma V, Ray P, Ray A. Formation and characterization of three dimensional human hepatocyte cell line spheroids on chitosan matrix for in vitro tissue engineering applications. In Vitro Cell Dev Biol Anim. 2007;43:328-37 pubmed
    ..These miniature "liver tissue like" models can be used for in vitro tissue engineering applications like preliminary evaluation of the toxicity of drugs and chemicals...
  57. Yu S, Ping Y, Yi L, Zhou Z, Chen J, Yao X, et al. Isolation and characterization of cancer stem cells from a human glioblastoma cell line U87. Cancer Lett. 2008;265:124-34 pubmed publisher
  58. Huygens A, Crnolatac I, Develter J, VAN Cleynenbreugel B, van der Kwast T, de Witte P. Differential accumulation of hypericin in spheroids composed of T-24 transitional cell carcinoma cells expressing different levels of E-cadherin. J Urol. 2008;179:2014-9 pubmed publisher
  59. Mimura T, Amano S, Yokoo S, Uchida S, Yamagami S, Usui T, et al. Tissue engineering of corneal stroma with rabbit fibroblast precursors and gelatin hydrogels. Mol Vis. 2008;14:1819-28 pubmed
    ..To isolate fibroblast precursors from rabbit corneal stroma using a sphere-forming assay, to engineer corneal stroma with the precursors and gelatin, and to establish the therapeutic application of precursors in a rabbit corneal stroma...
  60. Heida N, Leifheit Nestler M, Schroeter M, Muller J, Cheng I, Henkel S, et al. Leptin enhances the potency of circulating angiogenic cells via src kinase and integrin (alpha)vbeta5: implications for angiogenesis in human obesity. Arterioscler Thromb Vasc Biol. 2010;30:200-6 pubmed publisher
    ..To investigate the capacity of the adipokine leptin to promote angiogenesis by modulating the function of circulating angiogenic cells (CACs)...
  61. Taylor M, Liu Y, Nagji A, Theodosakis N, Jones D. Combined proteasome and histone deacetylase inhibition attenuates epithelial-mesenchymal transition through E-cadherin in esophageal cancer cells. J Thorac Cardiovasc Surg. 2010;139:1224-32, 1232.e1 pubmed publisher
    ..This study investigated effects of vorinostat (histone deacetylase inhibitor) and bortezomib (proteasome inhibitor) on esophageal cancer epithelial-mesenchymal transition...
  62. Kim T, Mount C, Gombotz W, Pun S. The delivery of doxorubicin to 3-D multicellular spheroids and tumors in a murine xenograft model using tumor-penetrating triblock polymeric micelles. Biomaterials. 2010;31:7386-97 pubmed publisher
    ..Finally, DOX-loaded micelles mediate efficient tumor delivery from tail vein injections to tumor-bearing mice with much less toxicity compared with free DOX...
  63. Li H, Zhou X. Potential conversion of adult clavicle-derived chondrocytes into neural lineage cells in vitro. J Cell Physiol. 2008;214:630-44 pubmed
    ..The possible de-differentiation/trans-differentiation mechanisms underlying the conversion were discussed...
  64. Chin W, Heng P, Lim P, Lau W, Olivo M. Membrane transport enhancement of chlorin e6-polyvinylpyrrolidone and its photodynamic efficacy on the chick chorioallantoic model. J Biophotonics. 2008;1:395-407 pubmed publisher
    ..The present work contributes to our understanding of the Ce6-PVP drug-polymer system by demonstrating for the first time that the presence of PVP facilitates the transport of Ce6 across the chorioallantoic membrane...
  65. Elberg G, Elberg D, Lewis T, Guruswamy S, Chen L, Logan C, et al. EP2 receptor mediates PGE2-induced cystogenesis of human renal epithelial cells. Am J Physiol Renal Physiol. 2007;293:F1622-32 pubmed
    ..The role of EP2 receptor in mediating the PGE2 effect on stimulating cyst formation may have direct pharmacological implications for the treatment of polycystic kidney disease...
  66. Liao Q, Hu Y, Zhao Y, Zhou T, Zhang Q. Assessment of pancreatic carcinoma cell chemosensitivity using a three-dimensional culture system. Chin Med J (Engl). 2010;123:1871-7 pubmed
  67. Srivastava V, Nalbantoglu J. Flow cytometric characterization of the DAOY medulloblastoma cell line for the cancer stem-like phenotype. Cytometry A. 2008;73:940-8 pubmed publisher
    ..As such, care must be used in interpreting therapeutic studies targeting the stem cell compartment of cancer cell lines...
  68. Oka N, Soeda A, Noda S, Iwama T. Brain tumor stem cells from an adenoid glioblastoma multiforme. Neurol Med Chir (Tokyo). 2009;49:146-50; discussion 150-1 pubmed
    ..Methods to localize CSCs may open new approaches for the treatment of brain tumors...
  69. Li G, Chen Z, Hu Y, Wei H, Li D, Ji H, et al. Autocrine factors sustain glioblastoma stem cell self-renewal. Oncol Rep. 2009;21:419-24 pubmed
    ..Both the mRNA and protein of EGF and bFGF were detected in three human glioblastoma stem cells. Our findings suggest that autocrine of EGF and bFGF may sustain the self-renewal of glioblastoma stem cells...
  70. Frith J, Thomson B, Genever P. Dynamic three-dimensional culture methods enhance mesenchymal stem cell properties and increase therapeutic potential. Tissue Eng Part C Methods. 2010;16:735-49 pubmed publisher
    ..Our results showed that under optimal conditions, MSCs form compact cellular spheroids and remain viable in dynamic 3D culture...
  71. Hsiao A, Torisawa Y, Tung Y, Sud S, Taichman R, Pienta K, et al. Microfluidic system for formation of PC-3 prostate cancer co-culture spheroids. Biomaterials. 2009;30:3020-7 pubmed publisher
  72. Held Feindt J, Hattermann K, Müerköster S, Wedderkopp H, Knerlich Lukoschus F, Ungefroren H, et al. CX3CR1 promotes recruitment of human glioma-infiltrating microglia/macrophages (GIMs). Exp Cell Res. 2010;316:1553-66 pubmed publisher
    ..These data indicate that the CX3CL1/CX3CR1 system has a crucial tumor-promoting role in human glioblastomas via its impact on glioma-infiltrating immune subsets...
  73. Neti P, Howell R. Biological response to nonuniform distributions of (210)Po in multicellular clusters. Radiat Res. 2007;168:332-40 pubmed
    ..Neither the mean cluster absorbed dose nor a semi-empirical multicellular dosimetry approach could accurately predict the lethal effects of (210)Po-citrate...
  74. Farnie G, Clarke R. Mammary stem cells and breast cancer--role of Notch signalling. Stem Cell Rev. 2007;3:169-75 pubmed
  75. Karpowicz P, Willaime Morawek S, Balenci L, DeVeale B, Inoue T, van der Kooy D. E-Cadherin regulates neural stem cell self-renewal. J Neurosci. 2009;29:3885-96 pubmed publisher
    ..These data show the importance of E-Cadherin in the neural stem cell niche and suggest E-Cadherin regulates the number of these cells...
  76. Robertson F, Ogasawara M, Ye Z, Chu K, Pickei R, Debeb B, et al. Imaging and analysis of 3D tumor spheroids enriched for a cancer stem cell phenotype. J Biomol Screen. 2010;15:820-9 pubmed publisher
  77. Ernst A, Hofmann S, Ahmadi R, Becker N, Korshunov A, Engel F, et al. Genomic and expression profiling of glioblastoma stem cell-like spheroid cultures identifies novel tumor-relevant genes associated with survival. Clin Cancer Res. 2009;15:6541-50 pubmed publisher
    ..We exploited the glioma spheroid culture model to find novel tumor-relevant genes...
  78. Gakhar Koppole N, Hundeshagen P, Mandl C, Weyer S, Allinquant B, Müller U, et al. Activity requires soluble amyloid precursor protein alpha to promote neurite outgrowth in neural stem cell-derived neurons via activation of the MAPK pathway. Eur J Neurosci. 2008;28:871-82 pubmed publisher
    ..In summary, these experiments indicate a novel role of APP family members in activity-dependent neuronal differentiation...
  79. Sodek K, Ringuette M, Brown T. Compact spheroid formation by ovarian cancer cells is associated with contractile behavior and an invasive phenotype. Int J Cancer. 2009;124:2060-70 pubmed publisher
    ..Preventing the formation of ovarian cancer spheroids may represent a novel strategy to improve the efficacy of existing therapeutics...
  80. Storci G, Sansone P, Mari S, D Uva G, Tavolari S, Guarnieri T, et al. TNFalpha up-regulates SLUG via the NF-kappaB/HIF1alpha axis, which imparts breast cancer cells with a stem cell-like phenotype. J Cell Physiol. 2010;225:682-91 pubmed publisher
    ..Our results reveal a molecular mechanism whereby TNF?, a major pro-inflammatory cytokine, imparts breast cancer cells with stem cell-like features, which are connected to increased tumor aggressiveness...
  81. Hartung O, Huo H, Daley G, Schlaeger T. Clump passaging and expansion of human embryonic and induced pluripotent stem cells on mouse embryonic fibroblast feeder cells. Curr Protoc Stem Cell Biol. 2010;Chapter 1:Unit 1C.10 pubmed publisher
    ..These conditions provide the basis for relatively inexpensive maintenance and expansion of hESCs, as well as their engineered counterparts, human induced pluripotent stem cells (hiPSCs)...
  82. Chatni M, Porterfield D. Self-referencing optrode technology for non-invasive real-time measurement of biophysical flux and physiological sensing. Analyst. 2009;134:2224-32 pubmed publisher
    ..In this paper, we show the calibration, characterization and application of the self-referencing oxygen optrode for measuring biophysical oxygen flux...
  83. Bergstrom M, Monazzam A, Razifar P, Ide S, Josephsson R, Langstrom B. Modeling spheroid growth, PET tracer uptake, and treatment effects of the Hsp90 inhibitor NVP-AUY922. J Nucl Med. 2008;49:1204-10 pubmed publisher
    ..In addition, we demonstrated how this information can be used for planning clinical trials...
  84. Lombaert I, Brunsting J, Wierenga P, Faber H, Stokman M, Kok T, et al. Rescue of salivary gland function after stem cell transplantation in irradiated glands. PLoS ONE. 2008;3:e2063 pubmed publisher
    ..Our approach is the first proof for the potential use of stem cell transplantation to functionally rescue salivary gland deficiency...
  85. Frongia C, Lorenzo C, Gianni F, Prevost G, Ducommun B, Lobjois V. 3D imaging of the response to CDC25 inhibition in multicellular spheroids. Cancer Biol Ther. 2009;8:2230-36 pubmed
    ..These results emphasize the importance of 3D models and of in toto analysis for the evaluation of anticancer drugs cytotoxicity...
  86. Sasaki R, Aoki S, Yamato M, Uchiyama H, Wada K, Okano T, et al. Neurosphere generation from dental pulp of adult rat incisor. Eur J Neurosci. 2008;27:538-48 pubmed publisher
    ..These data suggest that the CD81 and nestin double-positive cells localized in the odontoblast layer of the apical portion of the dental pulp may have the ability to grow and form neurospheres...
  87. Storz P, Döppler H, Copland J, Simpson K, Toker A. FOXO3a promotes tumor cell invasion through the induction of matrix metalloproteinases. Mol Cell Biol. 2009;29:4906-17 pubmed publisher
  88. Aressy B, Bugler B, Valette A, Biard D, Ducommun B. Moderate variations in CDC25B protein levels modulate the response to DNA damaging agents. Cell Cycle. 2008;7:2234-40 pubmed
  89. Chaichana K, Guerrero Cazares H, Capilla Gonzalez V, Zamora Berridi G, Achanta P, Gonzalez Perez O, et al. Intra-operatively obtained human tissue: protocols and techniques for the study of neural stem cells. J Neurosci Methods. 2009;180:116-25 pubmed publisher
    ..This study describes in detail both current and newly developed laboratory techniques, which in our experience are used to process and study human NSCs and BTSCs from tissue obtained directly from the operating room...
  90. Fernandes K, Miller F. Isolation, expansion, and differentiation of mouse skin-derived precursors. Methods Mol Biol. 2009;482:159-70 pubmed publisher
    ..Here, we detail the establishment, propagation, neural differentiation, and immunocytochemical analysis of SKP cultures...