Skip to main content
SpringerLink
Log in

Quality control of cultured tissues requires tools for quantitative analyses of heterogeneous features developed in manufacturing process

  • Published:
Cell and Tissue Banking Aims and scope Submit manuscript

Abstract

Tissue engineering and related technology have attracted a great deal of medical attention as promising fields for curing defective tissues in vivo. Nowadays, many companies have been established for supplying the reconstructed grafts of cultured tissues for transplantation. The manufacturing processes generally deals with the handlings of starter cells offered by patients (or donors) as raw materials to cultured tissues as products, requiring the construction of novel ex vivo methodologies based on principles different from conventional processes for chemical and pharmaceutical productions. In addition, the raw materials have heterogeneity depending on the state of patients and location of cell harvests, and the products possess spatial cell distribution in the three dimensional structure. These features request a unique strategy in manufacturing process accompanied with the quality control for raw materials and products. This review article describes the contribution of tissue bankers and biochemical engineers to the quality control of cultured tissues during manufacturing, introducing the advances in methodologies to evaluate spatial heterogeneity of cells (or aggregates) and matrices in cultured tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Alotto D, Ariotti S, Graziano S, Verrua R, Stella M, Magliacani G, Castagnoli C (2002) The role of quality control in a skin bank: tissue viability determination. Cell Tissue Bank 3:3–10

    Article  PubMed  CAS  Google Scholar 

  • Ben-Bassat H (2005) Performance and safety of skin allografts. Clin Derm 23:365–375

    Article  Google Scholar 

  • Ben-Bassat H, Chaouat M, Zumai E, Segal N, Cinamon U, Ron M, Wexler MR, Eldad A (2000) The Israel national skin bank: quality assurance and graft performance of stored tissues. Cell Tissue Bank 1:303–312

    Article  PubMed  Google Scholar 

  • Benya PD, Padilla SR, Nimni ME (1987) Independent regulation of collagen types by chondrocytes during the loss of differentiated function in culture. Cell 15:1313–1321

    Article  Google Scholar 

  • Benya PD, Shaffer JD (1982) Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 30:215–224

    Article  PubMed  CAS  Google Scholar 

  • Boyce ST (2004) Fabrication, quality assurance, and assessment of cultured skin substitutes for treatment of skin wounds. Biochem Eng J 20:107–112

    Article  CAS  Google Scholar 

  • Campagnola PJ, Wei M, Lewis A, Loew LM (1999) High-resolution nonlinear imaging of live cells by second harmonic generation. Biophys J 77:3341–3349

    Article  PubMed  CAS  Google Scholar 

  • Chubinskaya S, Huch K, Schulze M, Otten L, Aydelotte MB, Cole AA (2001) Gene expression by human articular chondrocytes cultured in alginate beads. J Histochem Cytochem 49:1211–1219

    PubMed  CAS  Google Scholar 

  • Diaz-Romero J, Gaillard JP, Grogan SP, Nesic D, Trub T, Mainil-Varlet P (2005) Immunophenotypic analysis of human articular chondrocytes: changes in surface markers associated with cell expansion in monolayer culture. J Cell Physiol 202:731–742

    Article  PubMed  CAS  Google Scholar 

  • Dickinson SC, Sims TJ, Pittarello L, Soranzo C, Pavesio A, Hollander AP (2005) Quantitative outcome measures of cartilage repair in patients treated by tissue engineering. Tissue Eng 11:277–287

    Article  PubMed  Google Scholar 

  • du Moulin GC, Morohashi M (2000) Development of a regulatory strategy for the cellular therapies: an American perspective. Mater Sci Eng C 13:15–17

    Article  Google Scholar 

  • Dunn JC, Chan WY, Cristini V, Kim JS, Lowengrub J, Singh S, Wu BM (2006) Analysis of cell growth in three-dimensional scaffolds. Tissue Eng 12:705–716

    Article  PubMed  CAS  Google Scholar 

  • Farrugia A (2006) When do tissues and cells become products?—Regulatory oversight of emerging biological therapies. Cell Tissue Bank 7:325–335

    Article  PubMed  Google Scholar 

  • Freed LE, Guilak F, Guo XE, Gray ML, Tranquillo R, Holmes JW, Radisic M, Sefton MV, Kaplan D, Vunjak-Novakovic G (2006) Advanced tools for tissue engineering: scaffolds, bioreactors, and signaling. Tissue Eng 12:3285–3305

    Article  PubMed  CAS  Google Scholar 

  • Fujimoto JG (2003) Optical coherence tomography for ultrahigh resolution in vivo imaging. Nat Biotechnol 21:1361–1367

    Article  PubMed  CAS  Google Scholar 

  • Gaudet C, Marganski WA, Kim S, Brown CT, Gunderia V, Dembo M, Joyce YW (2003) Influence of type I collagen surface density on fibroblast spreading, motility, and contractility. Biophys J 85:3329–3335

    Article  PubMed  CAS  Google Scholar 

  • Goessler UR, Hormann K, Riedel F (2004) Tissue engineering with chondrocytes and function of the extracellular matrix. Int J Mol Med 13:505–513

    PubMed  CAS  Google Scholar 

  • Goessler UR, Bieback K, Bugert P, Heller T, Sadick H, Hormann K, Riedel F (2006) In vitro analysis of integrin expression during chondrogenic differentiation of mesenchymal stem cells and chondrocytes upon dedifferentiation in cell culture. Int J Mol Med 17:301–307

    PubMed  CAS  Google Scholar 

  • Grogan SP, Barbero A, Winkelmann V, Rieser F, Fitzsimmons JS, O’Driscoll S, Martin I, Mainil-Varlet P (2006) Visual histological grading system for the evaluation of in vitro-generated neocartilage. Tissue Eng 12:2141–2149

    Article  PubMed  Google Scholar 

  • Hauselmann HJ, Fernandas RJ, Mok SS, Schmid TM, Block JA, Aydelotte MB, Kuettner KE, Thonar EJ-MA (1994) Phenotypic stability of bovine articular chondrocytes after long-term culture in alginate beads. J Cell Sci 269:15265–15273

    Google Scholar 

  • Hendriks J, Riesle J, Vanblitterswijk CA (2006) Effect of stratified culture compared to confluent culture in monolayer on proliferation and differentiation of human articular chondrocytes. Tissue Eng 12:2397–2405

    Article  PubMed  CAS  Google Scholar 

  • Heywood HK, Sembi PK, Lee DA, Bader DL (2004) Cellular utilization determines viability and matrix distribution profiles in chondrocyte-seeded alginate constructs. Tissue Eng 10:1467–1479

    PubMed  CAS  Google Scholar 

  • Ingber DE, Mow VC, Butler D, Niklason L, Huard J, Mao J, Yannas I, Kaplan D, Vunjak-Novakovic G (2006) Tissue engineering and developmental biology: going biomimetic. Tissue Eng 12:3265–3283

    Article  PubMed  CAS  Google Scholar 

  • Ireland L, Spelman D (2005) Bacterial contamination of tissue allografts—experiences of the donor tissue bank of Victoria. Cell Tissue Bank 6:181–189

    Article  PubMed  Google Scholar 

  • Jadin KD, Wong BL, Bae WC, Li KW, Williamson AK, Schumacher BL, Price JH, Sah RL (2005) Depth-varying density and organization of chondrocytes in immature and mature bovine articular cartilage assessed by 3D imaging and analysis. J Histochem Cytochem 53:1109–1119

    Article  PubMed  CAS  Google Scholar 

  • Jadin KD, Bae WC, Schumacher BL, Sah RL (2007) Three-dimensional (3-D) imaging of chondrocytes in articular cartilage: growth-associated changes in cell organization. Biomaterials 28:230–239

    Article  PubMed  CAS  Google Scholar 

  • Jones CW, Smolinski D, Keogh A, Kirk TB, Zheng MH (2005) Confocal laser scanning microscopy in orthopaedic research. Prog Histochem Cytochem 40:1–71

    Article  PubMed  CAS  Google Scholar 

  • Kinnunen M, Myllylä R, Jokela T, Vainio S (2006) In vitro studies toward noninvasive glucose monitoring with optical coherence tomography. Appl Opt 45:2251–2260

    Article  PubMed  CAS  Google Scholar 

  • Kino-oka M, Taya M (2004) Development of culture techniques of keratinocytes for skin graft production. In: Kobayashi T (ed) Adv Biochem Eng/Biotechnol, vol 91. Springer-Verlag, Berlin, pp 135–169

    Google Scholar 

  • Kino-oka M, Taya M (2005) Design and operation of a radial flow bioreactor for reconstruction of cultured tissues. In: Chaudhuri J, Al-Rubeai M (eds) Bioreactors for Tissue Engineering: Principles, Design and Operation. Springer, Dordrecht, pp 115–134

    Chapter  Google Scholar 

  • Kino-oka M, Maeda Y, Yamamoto T, Sugawara K, Taya M (2005a) A kinetic modeling of chondrocyte culture for manufacture of tissue-engineered cartilage. J Biosci Bioeng 99:197–207

    Article  PubMed  CAS  Google Scholar 

  • Kino-oka M, Yashiki S, Ota Y, Mushiaki Y, Sugawara K, Yamamoto T, Takezawa T, Taya M (2005b) Subculture of chondrocytes on a collagen type-I coated substrate with suppressed cellular dedifferentiation. Tissue Eng 11:597–608

    Article  PubMed  CAS  Google Scholar 

  • Kino-oka M, Maeda Y, Ota Y, Yashiki S, Sugawara K, Yamamoto T, Taya M (2005c) Process design of chondrocyte cultures with monolayer growth for cell expansion and subsequent three-dimensional growth for production of cultured cartilage. J Biosci Bioeng 100:67–76

    Article  PubMed  CAS  Google Scholar 

  • Kino-oka M, Maeda Y, Sato Y, Khoshfetrat AB, Yamamoto T, Sugawara K, Taya M (2007) Characterization of spatial growth and distribution of chondrocyte cells embedded in collagen gels through a stereoscopic cell imaging system. Biotechnol Bioeng 99:1230–1240

    Article  CAS  Google Scholar 

  • Kostiak PE (2000) The evolution of quality systems in human bone banking: the U.S. experience. Cell Tissue Bank 1:155–160

    Article  PubMed  Google Scholar 

  • Lee DA, Reisler T, Badar DL (2003) Expansion of chondrocytes for tissue engineering in alginate beads enhances chondrocytic phenotype compared to conventional monolayer techniques. Acta Orthop Scand 74:6–15

    Article  PubMed  Google Scholar 

  • Lipson SM, Svenssen L, Goodwin L, Porti D, Danzi S, Pergolizzi R (2001) Evaluation of two current generation enzyme immunoassays and an improved isolation-based assay for the rapid detection and isolation of rotavirus from stool. J Clin Virol 21:17–27

    Article  PubMed  CAS  Google Scholar 

  • Malarkey M, Solomon R, Witten C, Bloom E, Wells M, Braun M, Wise R, Zinderman C, Jernigan DB, Kuehnert MJ, Srinivasan A, Wang S (2006) Brief report: investigation into recalled human tissue for transplantation—United States, 2005–2006. J Am Med Assoc 296:1347–1348

    Article  CAS  Google Scholar 

  • Mankin HJ, Dorfman H, Lippiello L, Zarins A (1971) Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am 53:523–537

    PubMed  CAS  Google Scholar 

  • Martin I, Vunjak-Ncakovic G, Yang J, Langer R, Freed LE (1999) Mammalian chondrocytes expanded in the presence of fibroblast growth factor 2 maintain the ability to differentiate and regenerate three-dimensional cartilaginous tissue. Exp Cell Res 253:681–688

    Article  PubMed  CAS  Google Scholar 

  • Mason C, Hoare M (2007) Regenerative medicine bioprocessing: building a conceptual framework based on early studies. Tissue Eng 13:301–311

    Article  PubMed  CAS  Google Scholar 

  • Mayhew TA, Williams GR, Senica MA, Kuniholm G, Du Moulin GC (1998) Validation of a quality assurance program for autologous cultured chondrocyte implantation. Tissue Eng 4:325–334

    Article  PubMed  CAS  Google Scholar 

  • Mizuno S, Allemann F, Glowacki J (2001) Effects of medium perfusion on matrix production by bovine chondrocytes in three-dimensional collagen sponges. J Biomed Mater Res 56:368–375

    Article  PubMed  CAS  Google Scholar 

  • Moojen DJ, Saris DB, Auw Yang KG, Dhert WJ, Verbout AJ (2002) The correlation and reproducibility of histological scoring systems in cartilage repair. Tissue Eng 8:627–634

    Article  PubMed  CAS  Google Scholar 

  • Nerem RM, Sambanis A (1995) Tissue engineering: from biology to biological substitutes. Tissue Eng 1:3–13

    Article  Google Scholar 

  • Neubauer A, Priglinger SG, Thiel MJ, May CA, Welge-Lüßen UC (2002) Sterile structural imaging of donor cornea by optical coherence tomography. Cornea 21:490–494

    Article  PubMed  Google Scholar 

  • Nguyen H, Morgan DAF, Forwood FR (2006) Sterilization of allograft bone: is 25 kGy the gold dtandard for gamma irradiation? Cell Tissue Bank 8:81–91

    Article  PubMed  Google Scholar 

  • Ochi M, Adachi N, Nobuto H, Yanada S, Ito Y, Agung M (2004) Articular cartilage repair using tissue engineering technique—novel approach with minimally invasive procedure. Artif Organs 28:28–32

    Article  PubMed  Google Scholar 

  • O’Driscoll SW, Marx RG, Beaton DE, Miura Y, Gallay SH, Fitzsimmons JS (2001) Validation of a simple histological-histochemical cartilage scoring system. Tissue Eng 7:313–320

    Article  PubMed  CAS  Google Scholar 

  • Omstead DR, Baird LG, Christenson L, du Moulin GC, Tubo R, Mazted DD, Davis J, Gentile FT (1998) Voluntary guidance for the development of tissue-engineered products. Tissue Eng 4:239–266

    Article  PubMed  CAS  Google Scholar 

  • Park K, Huang J, Azar F, Jin RL, Min BH, Han DK, Hasty K (2006) Scaffold-free, engineered porcine cartilage construct for cartilage defect repair in vitro and in vivo study. Artif Organs 30:586–596

    Article  PubMed  CAS  Google Scholar 

  • Provenzano PP, Eliceiri KW, Campbell JM, Inman DR, White JG, Keely PJ (2006) Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med 4:38

    Article  PubMed  CAS  Google Scholar 

  • Rahman MS, Tsuchiya T (2001) Enhancement of chondrogenic differentiation of human articular chondrocytes by biodegradable polymers. Tissue Eng 7:781–790

    Article  PubMed  CAS  Google Scholar 

  • Ramrattan NN, Heijkants RG, van Tienen TG, Schouten AJ, Veth RP, Buma P (2005) Assessment of tissue ingrowth rates in polyurethane scaffolds for tissue engineering. Tissue Eng 11:1212–1223

    Article  PubMed  CAS  Google Scholar 

  • Sandusky GE, Teheny KH, Esterman M, Hanson J, Williams SD (2007) Quality control of human tissues-experience from the Indiana University Cancer Center-Lilly Research Labs human tissue bank. Cell Tissue Bank 9:287–295

    Article  Google Scholar 

  • Shakibaei M, Merker HJ (1999) β1-Integrins in the cartilage matrix. Cell Tissue Res 296:565–573

    Article  PubMed  CAS  Google Scholar 

  • Shakibaei M, Abou-Rebyeh H, Merker HJ (1993) Integrins in ageing cartilage tissue in vitro. Histol Histopathol 8:715–723

    PubMed  CAS  Google Scholar 

  • Shakibaei M, de Souza P, Merker HJ (1997) Integrin expression and collagen type 2 implicated in maintenance of chondrocyte shape in monolayer culture: an immunomorphological study. Cell Biol Int 21:115–125

    Article  PubMed  CAS  Google Scholar 

  • Spangenberg KM, Peretti GM, Trahan CA, Randolph MA, Bonassar LJ (2002) Histomorphometric analysis of a cell-based model of cartilage repair. Tissue Eng 8:839–846

    Article  PubMed  Google Scholar 

  • Tatarenko A (2006) European regulations and their impact on tissue banking. Cell Tissue Bank 7:231–235

    Article  PubMed  Google Scholar 

  • von der Mark K, Gauss V, von der Mark H, Muller P (1977) Relationship between cell shape and type of collagen synthesized as chondrocytes lose their cartilage phenotype in culture. Nature 267:531–532

    Article  Google Scholar 

  • Wakitani S, Kimura T, Hirooka A, Ochi T, Yoneda M, Yasui N, Owaki H, Ono K (1989) Repair of rabbit articular surfaces with allograft chondrocytes embedded in collagen gel. J Bone Joint Surg Br 71:74–80

    PubMed  CAS  Google Scholar 

  • Wang S, Zinderman C, Wise R, Braun M (2007) Infections and human tissue transplants: review of FDA MedWatch reports 2001–2004. Cell Tissue Bank 8:211–219

    Article  PubMed  Google Scholar 

  • Wendt D, Jakob M, Martin I (2005) Bioreactor-based engineering of osteochondral grafts: from model systems to tissue manufacturing. J Biosci Bioeng 100:489–494

    Article  PubMed  CAS  Google Scholar 

  • Xu X, Urban JP, Tirlapur U, Wu MH, Cui Z, Cui Z (2006) Influence of perfusion on metabolism and matrix production by bovine articular chondrocytes in hydrogel scaffolds. Biotechnol Bioeng 93:1103–1111

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto T, Katoh M, Fukushima R, Kurushima T, Ochi M (2002) Effect of glycosaminoglycan production on hardness of cultured cartilage fabricated by the collagen-gel embedding method. Tissue Eng 8:119–129

    Article  PubMed  CAS  Google Scholar 

  • Yang KG, Saris DB, Geuze RE, Helm YJ, Rijen MH, Verbout AJ, Dhert WJ, Creemers LB (2006) Impact of expansion and redifferentiation conditions on chondrogenic capacity of cultured chondrocytes. Tissue Eng 12:2435–2447

    Article  PubMed  CAS  Google Scholar 

  • Yaui T, Tohno Y, Araki T (2004) Determination of collagen fiber orientation in human tissue by use of polarization measurement of molecular second-harmonic-generation light. Appl Opt 43:2861–2867

    Article  Google Scholar 

Download references

Acknowledgements

This study was conducted as parts of the program “Center for integrated cell and tissue regulation” for Center of Excellent and the research program for Multidisciplinary Research Laboratory System organized in Graduate School of Engineering Science, Osaka University, and was in collaboration with Japan Tissue Engineering Co. Ltd., and was supported in part by Grant-in-Aid for Scientific Research on Priority Areas in the Ministry of Education, Culture, Sports, Science and Technology.

Author information

Authors and Affiliations

  1. Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama-cho, Toyonaka, Osaka, 560-8531, Japan

    Masahiro Kino-Oka, Yasunori Takezawa & Masahito Taya

Authors
  1. Masahiro Kino-Oka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasunori Takezawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masahito Taya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masahito Taya.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kino-Oka, M., Takezawa, Y. & Taya, M. Quality control of cultured tissues requires tools for quantitative analyses of heterogeneous features developed in manufacturing process. Cell Tissue Bank 10, 63–74 (2009). https://doi.org/10.1007/s10561-008-9103-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10561-008-9103-2

Keywords

Search

Navigation