Stem cells in drug discovery, tissue engineering, and regenerative medicine: Emerging opportunities and challenges

Journal of Biomolecular Screening

Volumn 14, Issue 7, 2009, Pages 755-768

  Nirmalanandhan, Victor Sanjit ^a   Sittampalam, G Sitta ^a  

^a UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

Author keywords

3D screening; Drug discovery; IPS cells; Regenerative medicine; Stem cells; Tissue engineering

Indexed keywords

ADULT STEM CELL; CANCER STEM CELL; CELL DIFFERENTIATION; DEGENERATIVE DISEASE; DEVELOPMENTAL BIOLOGY; EMBRYONIC STEM CELL; HEMATOPOIETIC STEM CELL; HUMAN; MEDICAL RESEARCH; MESENCHYMAL STEM CELL; MULTIPOTENT STEM CELL; NONHUMAN; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; REGENERATIVE MEDICINE; REVIEW; SCREENING; STEM CELL TRANSPLANTATION; TISSUE ENGINEERING; TISSUE REPAIR;

ANIMALS; DRUG DISCOVERY; HUMANS; INDUCED PLURIPOTENT STEM CELLS; NEOPLASTIC STEM CELLS; REGENERATIVE MEDICINE; STEM CELLS; TISSUE ENGINEERING;

ANIMALIA;

EID: 69549108053     PISSN: 10870571     EISSN: 1552454X     Source Type: Journal    
DOI: 10.1177/1087057109336591     Document Type: Review

References (110)

1. Klimanskaya I., Rosenthal N., Lanza R.: Derive and conquer: sourcing and differentiating stem cells for therapeutic applications. Nat Rev Drug Discov 2008 ; 7: 131-142.
2. Korbling M., Estrov Z.: Adult stem cells for tissue repair: a new therapeutic concept ? N Engl J Med 2003 ; 349: 570-582.
3. Collas P., Hakelien AM: Teaching cells new tricks. Trends Biotechnol 2003 ; 21: 354-361.
4. Rubin LL: Stem cells and drug discovery: the beginning of a new era? Cell 2008 ; 132: 549-552.
5. Pouton CW, Haynes JM: Embryonic stem cells as a source of models for drug discovery. Nat Rev Drug Discov 2007 ; 6: 605-616.
6. Ding S., Wu TY, Brinker A., Peters EC, Hur W., Gray NS, et al. Synthetic small molecules that control stem cell fate. Proc Natl Acad Sci USA 2003 ; 100: 7632-7637.
7. Wu X., Ding S., Ding Q., Gray NS, Schultz PG: Small molecules that induce cardiomyogenesis in embryonic stem cells. J Am Chem Soc 2004 ; 126: 1590-1591.
8. Ding S., Schultz PG: Small molecules and future regenerative medicine. Curr Top Med Chem 2005 ; 5: 383-395.
9. Cezar GG, Quam JA, Smith AM, Rosa GJ, Piekarczyk MS, Brown JF, et al. Identification of small molecules from human embryonic stem cells using metabolomics. Stem Cells Dev 2007 ; 16: 869-882.
10. Nicholson JK, Connelly J., Lindon JC, Holmes E.: Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov 2002 ; 1: 153-161.
11. The Nobel Prize in Physiology or Medicine 2007 [Press release]. October 8, 2007. Retrieved from: http://nobelprize.org/nobel-prizes/medicine/laureates/ 2007/press.html
12. Gearhart J., Pashos EE, Prasad MK: Pluripotency redux: advances in stem-cell research. N Engl J Med 2007 ; 357: 1469-1472.
13. US Department of Health and Human Services: 2020: A New Vision, a Future for Regenerative Medicine. Rockville, MD: US Department of Health and Human Services, 2005.
14. Lanza RP, Langer RS, Vacanti J, eds. Principles of Tissue Engineering. 2 nd ed. San Diego: Academic Press, 2000.
15. Guilak F., Butler DL, Goldstein SA, Mooney DJ: Functional Tissue Engineering. New York: Springer-Verlag, 2003.
16. Ramalho-Santos M., Willenbring H.: On the origin of the term "stem cell." Cell Stem Cell 2007 ; 1: 35-38.
17. National Institutes of Health: Stem Cell Basics. Retrieved from: http://stemcells.nih.gov/info/basics/
18. Tuch BE: Stem cells: a clinical update. Aust Fam Physician 2006 ; 35: 719-721.
19. Thomson JA, Itskovitz-Eldor J., Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998 ; 282: 1145-1147.
20. Hug K.: Therapeutic perspectives of human embryonic stem cell research versus the moral status of a human embryo: does one have to be compromised for the other? Medicina (Kaunas) 2006 ; 42: 107-114.
21. Takahashi K., Yamanaka S.: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006 ; 126: 663-676.
22. Wernig M., Meissner A., Foreman R., Brambrink T., Ku M., Hochedlinger K., et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 2007 ; 448: 318-324. (Pubitemid 47080337)
23. Yu J., Vodyanik MA, Smuga-Otto K., Antosiewicz-Bourget J., Frane JL, Tian S., et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007 ; 318: 1917-1920.
24. Takahashi K., Tanabe K., Ohnuki M., Narita M., Ichisaka T., Tomoda K., et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007 ; 131: 861-872.
25. Okita K., Ichisaka T., Yamanaka S.: Generation of germline-competent induced pluripotent stem cells. Nature 2007 ; 448: 313-317.
26. Maherali N., Sridharan R., Xie W., Utikal J., Eminli S., Arnold K., et al. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 2007 ; 1: 55-70.
27. Shi Y., Do JT, Desponts C., Hahm HS, Scholer HR, Ding S.: A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell 2008 ; 2: 525-528.
28. Park IH, Arora N., Huo H., Maherali N., Ahfeldt T., Shimamura A., et al. Disease-specific induced pluripotent stem cells. Cell 2008 ; 134: 877-886.
29. Sprangrude G., Heimfeld S., Weissman I.: Purification and characterization of mouse hematopoeitic stem cells. Science 1988 ; 241: 58-62.
30. Stemple DL, Anderson DJ: Isolation of a stem cell for neurons and glia from the mammalian neural crest. Cell 1992 ; 71: 973-985.
31. Malinin TI, Buck BE, Temple HT, Martinez OV, Fox WP: Incidence of clostridial contamination in donors musculoskeletal tissue. J Bone Joint Surg Br 2003 ; 85: 1051-1054.
32. Caplan AI: Mesenchymal stem cells. J Orthop Res 1991 ; 9: 641-650.
33. Caplan AI: The mesengenic process. Clin Plast Surg 1994 ; 21: 429-435.
34. Morrison SJ, Shah NM, Anderson DJ: Regulatory mechanisms in stem cell biology. Cell 1997 ; 88: 287-298.
35. Bruder SP, Fink DJ, Caplan AI: Mesenchymal stem cells in bone development, bone repair, and skeletal regeneration therapy. J Cell Biochem 1994 ; 56: 283-294.
36. Caplan A., Fink D., Goto T., Linton A., Young R., Wakitani S., et al. Mesenchymal stem cells and tissue repair. In Jackson D (ed): The ACL: Current and Future Concepts. New York: Raven, 1993.
37. Grigoriadis AE, Heersche JN, Aubin JE: Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone-derived clonal cell population: effect of dexamethasone. J Cell Biol 1988 ; 106: 2139-2151.
38. Young RG, Butler DL, Weber W., Caplan AI, Gordon SL, Fink DJ: Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair. J Orthop Res 1998 ; 16: 406-413.
39. Wakitani S., Goto T., Pineda SJ, Young RG, Mansour JM, Caplan AI, et al. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am 1994 ; 76: 579-592.
40. Awad HA, Boivin GP, Dressler MR, Smith FN, Young RG, Butler DL: Repair of patellar tendon injuries using a cell-collagen composite. J Orthop Res 2003 ; 21: 420-431.
41. Ouyang HW, Goh JC, Thambyah A., Teoh SH, Lee EH: Knitted polylactide-co-glycolide scaffold loaded with bone marrow stromal cells in repair and regeneration of rabbit Achilles tendon. Tissue Eng 2003 ; 9: 431-439.
42. Bonnet D., Dick JE: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997 ; 3: 730-737.
43. Hope KJ, Jin L., Dick JE: Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 2004 ; 5: 738-743.
44. Marx J.: Molecular biology: cancer's perpetual source? Science 2007 ; 317: 1029-1031.
45. Spillane JB, Henderson MA: Cancer stem cells: a review. ANZ J Surg 2007 ; 77: 464-468.
46. Bates J.: Cancer stem cells: emerging therapeutic, diagnostic and market opportunities. In BioPharm Reports. Lincolnshire, UK: VennBio, 2008.
47. Kelly PN, Dakic A., Adams JM, Nutt SL, Strasser A.: Tumor growth need not be driven by rare cancer stem cells. Science 2007 ; 317: 337.
48. Hill RP, Perris R.: "Destemming" cancer stem cells. J Natl Cancer Inst 2007 ; 99: 1435-1440.
49. Heasley LE, Petersen BE: Signalling in stem cells: meeting on signal transduction determining the fate of stem cells. EMBO Rep 2004 ; 5: 241-244.
50. Zhang J., Niu C., Ye L., Huang H., He X., Tong WG, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 2003 ; 425: 836-841.
51. Zhang J., Li L.: BMP signaling and stem cell regulation. Dev Biol 2005 ; 284: 1-11.
52. Reya T., Clevers H.: Wnt signalling in stem cells and cancer. Nature 2005 ; 434: 843-850. (Pubitemid 40558990)
53. Prakash N., Wurst W.: A Wnt signal regulates stem cell fate and differentiation in vivo. Neurodegener Dis 2007 ; 4: 333-338.
54. Mfopou JK, Bouwens L.: Hedgehog signals in pancreatic differentiation from embryonic stem cells: revisiting the neglected. Differentiation 2008 ; 76: 107-117.
55. Bani-Yaghoub M., Kendall SE, Moore DP, Bellum S., Cowling RA, Nikopoulos GN, et al. Insulin acts as a myogenic differentiation signal for neural stem cells with multilineage differentiation potential. Development 2004 ; 131: 4287-4298.
56. Bains W.: Failure rates in drug discovery and development: will we ever get any better? Drug Discov World 2004 ; 5: 9-18.
57. Tufts Center for the Study of Drug Development. Retrieved from: http://csdd.tufts.edu/NewsEvents/RecentNews.asp?newsid=4
58. Hubbell JA: Biomaterials science and high-throughput screening. Nat Biotechnol 2004 ; 22: 828-829.
59. Grimston SK, Screen J., Haskell JH, Chung DJ, Brodt MD, Silva MJ, et al. Role of connexin43 in osteoblast response to physical load. Ann N Y Acad Sci 2006 ; 1068: 214-224.
60. Cevallos M., Riha GM, Wang X., Yang H., Yan S., Li M., et al. Cyclic strain induces expression of specific smooth muscle cell markers in human endothelial cells. Differentiation 2006 ; 74: 552-561.
61. Chess PR, O'Reilly MA, Sachs F., Finkelstein JN: Reactive oxidant and p42/44 MAP kinase signaling is necessary for mechanical strain-induced proliferation in pulmonary epithelial cells. J Appl Physiol 2005 ; 99: 1226-1232.
62. McAdams RM, Mustafa SB, Shenberger JS, Dixon PS, Henson BM, DiGeronimo RJ: Cyclic stretch attenuates effects of hyperoxia on cell proliferation and viability in human alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol 2006 ; 291: L166 - L174.
63. Clarke MS, Feeback DL: Mechanical load induces sarcoplasmic wounding and FGF release in differentiated human skeletal muscle cultures. FASEB J 1996 ; 10: 502-509.
64. Cattaruzza M., Dimigen C., Ehrenreich H., Hecker M.: Stretch-induced endothelin B receptor-mediated apoptosis in vascular smooth muscle cells. FASEB J 2000 ; 14: 991-998.
65. Lee EK, Lee JS, Park HS, Kim CH, Gin YJ, Son Y.: Cyclic stretch stimulates cell proliferation of human mesenchymal stem cells but do not induce their apoptosis and differentiation. Tissue Eng Regenerative Med 2005 ; 2: 29-33.
66. Nirmalanandhan VS, Dressler MR, Shearn JT, Juncosa-Melvin N., Rao M., Gooch C., et al. Mechanical stimulation of tissue engineered tendon constructs: effect of scaffold materials. J Biomech Eng 2007 ; 129: 919-923.
67. Walsh MF, Woo RK, Gomez R., Basson MD: Extracellular pressure stimulates colon cancer cell proliferation via a mechanism requiring PKC and tyrosine kinase signals. Cell Prolif 2004 ; 37: 427-441.
68. Lawler K., Meade G., O'Sullivan G., Kenny D.: Shear stress modulates the interaction of platelet-secreted matrix proteins with tumor cells through the integrin alphavbeta3. Am J Physiol Cell Physiol 2004 ; 287: C1320 - C1327.
69. von Sengbusch A., Gassmann P., Fisch KM, Enns A., Nicolson GL, Haier J.: Focal adhesion kinase regulates metastatic adhesion of carcinoma cells within liver sinusoids. Am J Pathol 2005 ; 166: 585-596.
70. Li L., Xie T.: Stem cell niche: structure and function. Annu Rev Cell Dev Biol 2005 ; 21: 605-631.
71. Han HJ, Russo J., Kohwi Y., Kohwi-Shigematsu T.: SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature 2008 ; 452: 187-193.
72. Angele P., Kujat R., Nerlich M., Yoo J., Goldberg V., Johnstone B.: Engineering of osteochondral tissue with bone marrow mesenchymal progenitor cells in a derivatized hyaluronan-gelatin composite sponge. Tissue Eng 1999 ; 5: 545-554.
73. Awad HA, Boivin GP, Dressler MR, Simth FN, Young RG, Butler DL: Repair of patellar tendon injuries using a cell-collagen composite. J Orthop Res 2003 ; 21: 420-431.
74. Mauck RL, Soltz MA, Wang CC, Wong DD, Chao PH, Valhmu WB, et al. Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. J Biomech Eng 2000 ; 122: 252-260.
75. Stark HJ, Willhauck MJ, Mirancea N., Boehnke K., Nord I., Breitkreutz D., et al. Authentic fibroblast matrix in dermal equivalents normalises epidermal histogenesis and dermoepidermal junction in organotypic co-culture. Eur J Cell Biol 2004 ; 83: 631-645.
76. Powers MJ, Janigian DM, Wack KE, Baker CS, Beer Stolz D., Griffith LG: Functional behavior of primary rat liver cells in a three-dimensional perfused microarray bioreactor. Tissue Eng 2002 ; 8: 499-513.
77. Fukuda K.: Development of regenerative cardiomyocytes from mesenchymal stem cells for cardiovascular tissue engineering. Artif Organs 2001 ; 25: 187-193.
78. Anderson DG, Levenberg S., Langer R.: Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells. Nat Biotechnol 2004 ; 22: 863-866.
79. Lee MY, Kumar RA, Sukumaran SM, Hogg MG, Clark DS, Dordick JS: Three-dimensional cellular microarray for high-throughput toxicology assays. Proc Natl Acad Sci USA 2008 ; 105: 59-63.
80. Herrmann R., Fayad W., Schwarz S., Berndtsson M., Linder S.: Screening for compounds that induce apoptosis of cancer cells grown as multicellular spheroids. J Biomol Screen 2008 ; 13: 1-8.
81. Debnath J., Brugge JS: Modelling glandular epithelial cancers in three-dimensional cultures. Nat Rev Cancer 2005 ; 5: 675-688.
82. Kunz-Schughart LA, Freyer JP, Hofstaedter F., Ebner R.: The use of 3-D cultures for high-throughput screening: the multicellular spheroid model. J Biomol Screen 2004 ; 9: 273-285.
83. Dartsch PC, Hammerle H., Betz E.: Orientation of cultured arterial smooth muscle cells growing on cyclically stretched substrates. Acta Anatomica 1986 ; 125: 108-113.
84. Buck RC: Reorientation response of cells to repeated stretch and recoil of the substratum. Exp Cell Res 1980 ; 127: 470-474.
85. Buckley MJ, Banes AJ, Levin LG, Sumpio BE, Sato M., Jordan R., et al. Osteoblasts increase their rate of division and align in response to cyclic, mechanical tension in vitro. Bone Miner 1988 ; 4: 225-236.
86. Brighton CT, Strafford B., Gross SB, Leatherwood DF, Williams JL, Pollack SR: The proliferative and synthetic response of isolated calvarial bone cells of rats to cyclic biaxial mechanical strain. J Bone Joint Surg Am 1991 ; 73: 320-331.
87. Banes AJ, Gilbert J., Taylor D., Monbureau O.: A new vacuum-operated stress-providing instrument that applies static or variable duration cyclic tension or compression to cells in vitro. J Cell Sci 1985 ; 75: 35-42.
88. Altman GH, Horan RL, Martin I., Farhadi J., Stark PR, Volloch V., et al. Cell differentiation by mechanical stress. FASEB J 2002 ; 16: 270-272.
89. Zeichen J., van Griensven M., Bosch U.: The proliferative response of isolated human tendon fibroblasts to cyclic biaxial mechanical strain. Am J Sports Med 2000 ; 28: 888-892.
90. Skutek M., van Griensven M., Zeichen J., Brauer N., Bosch U.: Cyclic mechanical stretching modulates secretion pattern of growth factors in human tendon fibroblasts. Eur J Appl Physiol 2001 ; 86: 48-52. (Pubitemid 33725691)
91. Carver W., Nagpal ML, Nachtigal M., Borg TK, Terracio L.: Collagen expression in mechanically stimulated cardiac fibroblasts. Circ Res 1991 ; 69: 116-122.
92. Banes AJ, Horesovsky G., Larson C., Tsuzaki M., Judex S., Archambault J., et al. Mechanical load stimulates expression of novel genes in vivo and in vitro in avian flexor tendon cells. Osteoarthritis Cartilage 1999 ; 7: 141.
93. Langelier E., Rancourt D., Bouchard S., Lord C., Stevens P., Germain L., et al. Cyclic traction machine for long-term culture of fibroblast-populated collagen gels. Ann Biomed Eng 1999 ; 27: 67-72.
94. Cacou C., Palmer D., Lee DA, Bader DL, Shelton JC: A system for monitoring the response of uniaxial strain on cell seeded collagen gels. Med Eng Phys 2000 ; 22: 327-333.
95. Altman GH, Lu HH, Horan RL, Calabro T., Ryder D., Kaplan DL, et al. Advanced bioreactor with controlled application of multi-dimensional strain for tissue engineering. J Biomech Eng 2002 ; 124: 742-749.
96. Buckley MJ, Banes AJ, Jordan RD: The effects of mechanical strain on osteoblasts in vitro. J Oral Maxillofac Surg 1990 ; 48: 276-282 ; discussion 282-273.
97. Aguirre JI, Plotkin LI, Gortazar AR, Millan MM, O'Brien CA, Manolagas SC, et al. A novel ligand-independent function of the estrogen receptor is essential for osteocyte and osteoblast mechanotransduction. J Biol Chem 2007 ; 282: 25501-25508.
98. Adam RM, Eaton SH, Estrada C., Nimgaonkar A., Shih SC, Smith LE, et al. Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells. Physiol Genomics 2004 ; 20: 36-44.
99. Halachmi S., Aitken KJ, Szybowska M., Sabha N., Dessouki S., Lorenzo A., et al. Role of signal transducer and activator of transcription 3 (STAT3) in stretch injury to bladder smooth muscle cells. Cell Tissue Res 2006 ; 326: 149-158.
100. Gupta S., Sen S.: Myotrophin-kappaB DNA interaction in the initiation process of cardiac hypertrophy. Biochim Biophys Acta 2002 ; 1589: 247-260.
101. Liang F., Wu J., Garami M., Gardner DG: Mechanical strain increases expression of the brain natriuretic peptide gene in rat cardiac myocytes. J Biol Chem 1997 ; 272: 28050-28056.
102. Rannou F., Richette P., Benallaoua M., Francois M., Genries V., Korwin-Zmijowska C., et al. Cyclic tensile stretch modulates proteoglycan production by intervertebral disc annulus fibrosus cells through production of nitrite oxide. J Cell Biochem 2003 ; 90: 148-157.
103. Kiley SC, Thornhill BA, Tang SS, Ingelfinger JR, Chevalier RL: Growth factor-mediated phosphorylation of proapoptotic BAD reduces tubule cell death in vitro and in vivo. Kidney Int 2003 ; 63: 33-42.
104. Petermann AT, Pippin J., Durvasula R., Pichler R., Hiromura K., Monkawa T., et al. Mechanical stretch induces podocyte hypertrophy in vitro. Kidney Int 2005 ; 67: 157-166.
105. Durvasula RV, Shankland SJ: Mechanical strain increases SPARC levels in podocytes: implications for glomerulosclerosis. Am J Physiol Renal Physiol 2005 ; 289: F577 - F584.
106. Sakata R., Ueno T., Nakamura T., Ueno H., Sata M.: Mechanical stretch induces TGF-beta synthesis in hepatic stellate cells. Eur J Clin Invest 2004 ; 34: 129-136.
107. Frank JA, Wray CM, McAuley DF, Schwendener R., Matthay MA: Alveolar macrophages contribute to alveolar barrier dysfunction in ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 2006 ; 291: L1191 - L1198.
108. Breen EC: Mechanical strain increases type I collagen expression in pulmonary fibroblasts in vitro. J Appl Physiol 2000 ; 88: 203-209.
109. Le Bellego F., Plante S., Chakir J., Hamid Q., Ludwig MS: Differences in MAP kinase phosphorylation in response to mechanical strain in asthmatic fibroblasts. Respir Res 2006 ; 7: 68.
110. Kumar R., Yeh JJ, Fernandez D., Hansen N. Patent prosecution strategies for stem cell-related applications. J Biomol Screen 2007 ; 12: 769-774.