Review Article
The significance of cell-related challenges in the clinical application of tissue engineering
Thafar Almela,
Ian M. Brook,
Keyvan Moharamzadeh,
Thafar Almela
School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield, S10 2TA United Kingdom
Search for more papers by this authorIan M. Brook
School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield, S10 2TA United Kingdom
Search for more papers by this authorCorresponding Author
Keyvan Moharamzadeh
School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield, S10 2TA United Kingdom
Correspondence to: K. Moharamzadeh; e-mail: [email protected]Search for more papers by this authorThafar Almela,
Ian M. Brook,
Keyvan Moharamzadeh,
Thafar Almela
School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield, S10 2TA United Kingdom
Search for more papers by this authorIan M. Brook
School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield, S10 2TA United Kingdom
Search for more papers by this authorCorresponding Author
Keyvan Moharamzadeh
School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield, S10 2TA United Kingdom
Correspondence to: K. Moharamzadeh; e-mail: [email protected]Search for more papers by this authorAbstract
Tissue engineering is increasingly being recognized as a new approach that could alleviate the burden of tissue damage currently managed with transplants or synthetic devices. Making this novel approach available in the future for patients who would potentially benefit is largely dependent on understanding and addressing all those factors that impede the translation of this technology to the clinic. Cell-associated factors in particular raise many challenges, including those related to cell sources, up- and downstream techniques, preservation, and the creation of in vitro microenvironments that enable cells to grow and function as far as possible as they would in vivo. This article highlights the main confounding issues associated with cells in tissue engineering and how these issues may hinder the advancement of therapeutic tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3157–3163, 2016.
REFERENCES
- 1 Organ Procurement and Transplantation Network (OPTN). National Data. Available at: https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/[Accessed June 24, 2016].
- 2 Abou Neel EA, Chrzanowski W, Salih VM, Kim H-W, Knowles JC. Tissue engineering in dentistry. J Dent 2014; 42: 915–928.
- 3 Vacanti CA. The history of tissue engineering. J Cell Mol Med 2006; 10: 569–576.
- 4 Birla R. Introduction to Tissue Engineering: Applications and Challenges. Piscataway, NJ: IEEE Press; 2014.
- 5 Kirouac DC, Zandstra PW. The systematic production of cells for cell therapies. Cell Stem Cell 2008; 3: 369–381.
- 6 Nerem RM. Tissue engineering: The hope, the hype, and the future. Tissue Eng 2006; 12: 1143–1150.
- 7 Griffith LG, Naughton G. Tissue engineering: Current challenges and expanding opportunities. Science 2002; 295: 1009–1014.
- 8 Palakkan AA, Hay DC, Anil Kumar PR, Kumary TV, Ross JA. Liver tissue engineering and cell sources: Issues and challenges. Liver Int 2013; 33: 666–676.
- 9 Stock UA, Vacanti JP. Tissue engineering: Current state and prospects. Annu Rev Med 2001; 52: 443–451.
- 10
Kunisaki SM,
Fauza DO. Current state of clinical application. In: RP Lanza, RS Langer, JP Vacanti, editors. Principles of Tissue Engineering, 4th ed. Amsterdam: Elsevier/Academic Press; 2014. p 1687–1698.
10.1016/B978-0-12-398358-9.00080-X Google Scholar
- 11 Trainor N, Pietak A, Smith T. Rethinking clinical delivery of adult stem cell therapies. Nat Biotechnol 2014; 32: 729–735.
- 12
Freshney RI. Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, 6th ed. Hoboken, NJ: Wiley-Blackwell; 2010.
10.1002/9780470649367 Google Scholar
- 13 Bhagavati S. Stem cell therapy: Challenges ahead. Indian J Pediatr 2015; 82: 286–291.
- 14 Snippert HJ, Clevers H. Tracking adult stem cells. EMBO Rep 2011; 12: 113–122.
- 15 Di Battista J, Shebaby W, Kizilay O, Hamade E, Abou Merhi R, Mebarek S, et al. Proliferation and differentiation of human adipose-derived mesenchymal stem cells (ASCs) into osteoblastic lineage are passage dependent. Inflamm Res 2014; 63: 907–917.
- 16 El Tamer MK, Reis RL. Progenitor and stem cells for bone and cartilage regeneration. J Tissue Eng Regen Med 2009; 3: 327–337.
- 17 Choudhery MS, Badowski M, Muise A, Pierce J, Harris DT. Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation. J Transl Med 2014; 12: 8.
- 18 Li C, Wei G, Gu Q, Wen G, Qi B, Xu L, Tao S. Donor age and cell passage affect osteogenic ability of rat bone marrow mesenchymal stem cells. Cell Biochem Biophys 2015; 72: 543–549.
- 19 Røsland GV1, Svendsen A, Torsvik A, Sobala E, McCormack E, Immervoll H, Mysliwietz J, Tonn JC, Goldbrunner R, Lønning PE, Bjerkvig R, Schichor C. Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res 2009; 69: 5331–5339.
- 20 Serakinci N, Fahrioglu U, Christensen R. Mesenchymal stem cells, cancer challenges and new directions. Eur J Cancer 2014; 50: 1522–1530.
- 21 Martello G, Smith A. The nature of embryonic stem cells. Annu Rev Cell Dev Biol 2014; 30: 647–675.
- 22 Doerflinger RM. Old and new ethics in the stem cell debate. J Law Med Ethics 2010; 38: 212–219.
- 23 Santos MJ, Ventura-Juncá P. Bioethical aspects of basic research and medical applications of human stem cells. Biol Res 2012; 45: 317–326.
- 24 Grinnemo K-H, Sylvén C, Hovatta O, Dellgren G, Corbascio M. Immunogenicity of human embryonic stem cells. Cell Tissue Res 2008; 331: 67–78.
- 25 Tang C, Drukker M. Potential barriers to therapeutics utilizing pluripotent cell derivatives: Intrinsic immunogenicity of in vitro maintained and matured populations. Semin Immunopathol 2011; 33: 563–572.
- 26 Blum B, Benvenisty N. The tumorigenicity of diploid and aneuploid human pluripotent stem cells. Cell Cycle 2009; 8: 3822–3830.
- 27 Ben-David U, Benvenisty N. The tumorigenicity of human embryonic and induced pluripotent stem cells. Nat Rev Cancer 2011; 11: 268–277.
- 28 Dreesen O, Brivanlou AH. Signaling pathways in cancer and embryonic stem cells. Stem Cell Rev 2007; 3: 7–17.
- 29 Fujimori H, Shikanai M, Teraoka H, Masutani M, Yoshioka K. Induction of cancerous stem cells during embryonic stem cell differentiation. J Biol Chem 2012; 287: 36777–36791.
- 30 Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663–676.
- 31 Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131: 861–872.
- 32 Yu J, Thomson JA. Induced pluripotent stem cells. In: RP Lanza, RS Langer, JP Vacanti, editors. Principles of Tissue Engineering, 4th ed. Amsterdam: Elsevier/Academic Press; 2014. p 581–594.
- 33 Gore A, Li Z, Fung H-L, Young JE, Agarwal S, Antosiewicz-Bourget J, Canto I, et al. Somatic coding mutations in human induced pluripotent stem cells. Nature 2011; 471: 63–67.
- 34 Lee AS, Tang C, Rao MS, Weissman IL, Wu JC. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat Med 2013; 19: 998–1004.
- 35 Schoenhals M, Kassambara A, De Vos J, Hose D, Moreaux J, Klein B. Embryonic stem cell markers expression in cancers. Biochem Biophys Res Commun 2009; 383: 157–162.
- 36 Zhao T, Zhang Z-N, Rong Z, Xu Y. Immunogenicity of induced pluripotent stem cells. Nature 2011; 474: 212–215.
- 37 Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, et al. Epigenetic memory in induced pluripotent stem cells. Nature 2010; 467: 285–290.
- 38 Sullivan GJ, Bai Y, Fletcher J, Wilmut I. Induced pluripotent stem cells: Epigenetic memories and practical implications. Mol Hum Reprod 2010; 16: 880–885.
- 39 Abbasalizadeh S, Baharvand H. Technological progress and challenges towards cGMP manufacturing of human pluripotent stem cells based therapeutic products for allogeneic and autologous cell therapies. Biotechnol Adv 2013; 31: 1600–1623.
- 40 Serra M, Brito C, Correia C, Alves PM. Process engineering of human pluripotent stem cells for clinical application. Trends Biotechnol 2012; 30: 350–359.
- 41 Rodrigues CAV, Fernandes TG, Diogo MM, da Silva CL, Cabral JMS. Stem cell cultivation in bioreactors. Biotechnol Adv 2011; 29: 815–829.
- 42 Pörtner R, Nagel-Heyer S, Goepfert C, Adamietz P, Meenen NM. Bioreactor design for tissue engineering. J Biosci Bioeng 2005; 100: 235–245.
- 43 Rafiq QA, Coopman K, Hewitt CJ. Scale-up of human mesenchymal stem cell culture: Current technologies and future challenges. Curr Opin Chem Eng 2013; 2: 8–16.
- 44 Thomas RJ, Anderson D, Chandra A, Smith NM, Young LE, Williams D, Denning C. Automated, scalable culture of human embryonic stem cells in feeder-free conditions. Biotechnol Bioeng 2009; 102: 1636–1644.
- 45 Jin G, Yang GH, Kim G. Tissue engineering bioreactor systems for applying physical and electrical stimulations to cells. J Biomed Mater Res B Appl Biomater 2015; 103: 935–948.
- 46 Wang Y, Cheng L, Gerecht S. Efficient and scalable expansion of human pluripotent stem cells under clinically compliant settings: A view in 2013. Ann Biomed Eng 2014; 42: 1357–1372.
- 47 Rafiq QA, Brosnan KM, Coopman K, Nienow AW, Hewitt CJ. Culture of human mesenchymal stem cells on microcarriers in a 5 l stirred-tank bioreactor. Biotechnol Lett 2013; 35: 1233–1245.
- 48 Nienow AW, Rafiq QA, Coopman K, Hewitt CJ. A potentially scalable method for the harvesting of hMSCs from microcarriers. Biochem Eng J 2014; 85: 79–88.
- 49 Huang H-L, Hsing H-W, Lai T-C, Chen Y-W, Lee T-R, Chan H-T, et al. Trypsin-induced proteome alteration during cell subculture in mammalian cells. J Biomed Sci 2010; 17: 36
- 50 Brown MA, Wallace CS, Anamelechi CC, Clermont E, Reichert WM, Truskey GA. The use of mild trypsinization conditions in the detachment of endothelial cells to promote subsequent endothelialization on synthetic surfaces. Biomaterials 2007; 28: 3928–3935.
- 51 Sonnaert M, Luyten FP, Schrooten J, Papantoniou I. Bioreactor-based online recovery of human progenitor cells with uncompromised regenerative potential: A bone tissue engineering perspective. PLoS One 2015; 10: e0136875
- 52 Yang L, Cheng F, Liu T, Lu JR, Song K, Jiang L, et al. Comparison of mesenchymal stem cells released from poly (N-isopropylacrylamide) copolymer film and by trypsinization. Biomed Mater 2012; 7: 035003
- 53 Heng BC, Cowan CM, Basu S. Comparison of enzymatic and non-enzymatic means of dissociating adherent monolayers of mesenchymal stem cells. Biol Proced Online 2009; 11: 161–169.
- 54 Heng BC, Liu H, Ge Z, Cao T. Mechanical dissociation of human embryonic stem cell colonies by manual scraping after collagenase treatment is much more detrimental to cellular viability than is trypsinization with gentle pipetting. Biotechnol Appl Biochem 2007; 47: 33–37.
- 55 Qiu X, De Jesus J, Pennell M, Troiani M, Haun JB. Microfluidic device for mechanical dissociation of cancer cell aggregates into single cells. Lab Chip 2015; 15: 339–350.
- 56 Brandenberger R, Burger S, Campbell A, Fong T, Lapinskas E, Rowley JA. Cell therapy bioprocessing: Integrating process and product development for the next generation of biotherapeutics. BioProcess Int 2011; 9: S30–S37.
- 57 Wrigley JD, McCall EJ, Bannaghan CL, Liggins L, Kendrick C, Griffen A, et al. Cell banking for pharmaceutical research. Drug Discov Today 2014; 19: 1518–1529.
- 58 Hunt CJ. Cryopreservation of human stem cells for clinical application: A review. Transfus Med Hemother 2011; 38: 107–123.
- 59 Windrum P, Morris TCM, Drake MB, Niederwieser D, Ruutu T. EBMT Chronic Leukaemia Working Party Complications Subcommittee. Variation in dimethyl sulfoxide use in stem cell transplantation: A survey of EBMT centres. Bone Marrow Transplant 2005; 36: 601–603.
- 60 Cox MA, Kastrup J, Hrubiško M. Historical perspectives and the future of adverse reactions associated with haemopoietic stem cells cryopreserved with dimethyl sulfoxide. Cell Tissue Bank 2012; 13: 203–215.
- 61 Gatto C, Dainese L, Buzzi M, Terzi A, Guarino A, Pagliaro PP, et al. Establishing a procedure for dimethyl sulfoxide removal from cardiovascular allografts: A quantitative study. Cell Tissue Bank 2013; 14: 205–212.
- 62 Katkov II, Kim MS, Bajpai R, Altman YS, Mercola M, Loring JF, et al. Cryopreservation by slow cooling with DMSO diminished production of Oct-4 pluripotency marker in human embryonic stem cells. Cryobiology 2006; 53: 194–205.
- 63 Li Y, Tan J-C, Li L-S. Comparison of three methods for cryopreservation of human embryonic stem cells. Fertil Steril 2010; 93: 999–1005.
- 64
Eini F,
Foroutan T,
Bidadkosh A,
Barin A,
Dehghan MM,
Tajik P. The effects of freeze/thawing process on cryopreserved equine umbilical cord blood-derived mesenchymal stem cells. Comp Clin Pathol 2012; 21: 1713–1718.
10.1007/s00580-011-1355-8 Google Scholar
- 65 Serra M, Correia C, Malpique R, Brito C, Jensen J, Bjorquist P, et al. Microencapsulation technology: A powerful tool for integrating expansion and cryopreservation of human embryonic stem cells. PLoS One 2011; 6: e23212
- 66 Torsvik A, Røsland GV, Svendsen A, Molven A, Immervoll H, McCormack E, et al. Spontaneous malignant transformation of human mesenchymal stem cells reflects cross-contamination: Putting the research field on track – Letter. Cancer Res 2010; 70: 6393–6396.
- 67 Nikfarjam L, Farzaneh P. Prevention and detection of mycoplasma contamination in cell culture. Cell J 2012; 13: 203–212.
- 68 Placzek MR, Chung IM, Macedo HM, Ismail S, Mortera Blanco T, Lim M, et al. Stem cell bioprocessing: Fundamentals and principles. J R Soc Interface 2009; 6: 209–232.
- 69
Lim W,
Mayer B,
Pawson T. Cell Signaling: Principles and Mechanisms. New York: Garland Science; 2014.
10.1201/9780429258893 Google Scholar
- 70
Nerem RM,
Schutte SC. The challenge of imitating nature. In: RP Lanza, RS Langer, JP Vacanti, editors. Principles of Tissue Engineering, 4th ed. Amsterdam: Elsevier/Academic Press; 2014. p 9–24.
10.1016/B978-0-12-398358-9.00002-1 Google Scholar
- 71 Burdick JA, Vunjak-Novakovic G. Engineered microenvironments for controlled stem cell differentiation. Tissue Eng Part A 2009; 15: 205–219.
- 72
Luo Y,
Engelmayr G,
Auguste DT,
Ferreira LS,
Karp JM,
Saigal R,
Langer R. 3D scaffolds. In: RP Lanza, RS Langer, JP Vacanti, editors. Principles of Tissue Engineering, 4th ed. Amsterdam: Elsevier/Academic Press; 2014. p 475–494.
10.1016/B978-0-12-398358-9.00024-0 Google Scholar
- 73 Bhumiratana S, Cimetta E, Tandon N, Grayson W, Radisic M, Vunjak-Novakovic G. Tissue engineering bioreactors. In: J Fisher, AG Mikose, JD Bronzino, DR Peterson, editors. Tissue Engineering: Principles and Practices. Boca Raton, FL: CRC Press; 2013. Chapter 22.
- 74 Jain RK, Au P, Tam J, Duda DG, Fukumura D. Engineering vascularized tissue. Nat Biotechnol 2005; 23: 821–823.
- 75 Martin Y, Vermette P. Bioreactors for tissue mass culture: Design, characterization, and recent advances. Biomaterials 2005; 26: 7481–7503.
- 76 Kihara T, Ito J, Miyake J. Measurement of biomolecular diffusion in extracellular matrix condensed by fibroblasts using fluorescence correlation spectroscopy. PLoS One 2013; 8: e82382.
Citing Literature
