Regenerative medicine bioprocessing: building a conceptual framework based on early studies.

This paper reviews early studies of regenerative medicine using human cells and engineered tissues progressing from a laboratory-centered manual procedure toward automated manufacture. It then examines the distinctive bioprocesses by which autologous human material must be produced, the degree of simplification allowed by use of allogeneic cell lines and engineered tissue derived from them, and issues that affect both cell types. The paper concludes by drawing upon this discussion to suggest some factors that will determine how regenerative medicine bioprocessing can progress to provide many units of material economically.

[1]  A. Sambanis,et al.  Noninvasive measurement of viable cell number in tissue-engineered constructs in vitro, using 1H nuclear magnetic resonance spectroscopy. , 2005, Tissue engineering.

[2]  W. Ogier,et al.  Clinical Systems for the Production of Human Cells and Tissues , 1995, Bio/Technology.

[3]  S. Nadin-Davis,et al.  Viral contamination of embryos cryopreserved in liquid nitrogen. , 2000, Cryobiology.

[4]  Alois Knoll,et al.  Flexible Automation of Cell Culture and Tissue Engineering Tasks , 2004, Biotechnology progress.

[5]  G. Williams,et al.  Validation of a quality assurance program for autologous cultured chondrocyte implantation. , 1998, Tissue engineering.

[6]  Patrick Vermette,et al.  Bioreactors for tissue mass culture: design, characterization, and recent advances. , 2005, Biomaterials.

[7]  Wei Sun,et al.  Computer‐aided tissue engineering: overview, scope and challenges , 2004, Biotechnology and applied biochemistry.

[8]  J. Tramper,et al.  Current good manufacturing practice in plant automation of biological production processes , 2004, Cytotechnology.

[9]  D. Wendt,et al.  The role of bioreactors in tissue engineering. , 2004, Trends in biotechnology.

[10]  Ralf Pörtner,et al.  Bioreactor design for tissue engineering. , 2005, Journal of bioscience and bioengineering.

[11]  Antonella Farsetti,et al.  Epigenetic Histone Modification and Cardiovascular Lineage Programming in Mouse Embryonic Stem Cells Exposed to Laminar Shear Stress , 2005 .

[12]  P Dunnill,et al.  Doppler optical coherence tomography for measuring flow in engineered tissue. , 2004, Biosensors & bioelectronics.

[13]  Nigel Titchener-Hooker,et al.  Extreme scale‐down of expanded bed adsorption: Purification of an antibody fragment directly from recombinant E. coli culture , 2004, Biotechnology and bioengineering.

[14]  R. E. Spier,et al.  Animal Cell Technology: Developments, Processes, and Products , 1992 .

[15]  K. Niranjan,et al.  Observations on the shear damage to different animal cells in a concentric cylinder viscometer. , 2000, Biotechnology and bioengineering.

[16]  Glyn N. Stacey,et al.  Microbiological control in stem cell banks: approaches to standardisation , 2005, Applied Microbiology and Biotechnology.

[17]  Clemens A van Blitterswijk,et al.  A perfusion bioreactor system capable of producing clinically relevant volumes of tissue-engineered bone: in vivo bone formation showing proof of concept. , 2005, Biomaterials.

[18]  C R Culberson,et al.  Application of magnetic resonance microscopy to tissue engineering: a polylactide model. , 2002, Journal of biomedical materials research.

[19]  J. Duguid,et al.  Roadmap to approval: use of an automated sterility test method as a lot release test for Carticel, autologous cultured chondrocytes. , 2005, Cytotherapy.

[20]  Brett W. Bader,et al.  Fluid Mechanics, Cell Distribution, and Environment in Cell Cube Bioreactors , 2003, Biotechnology progress.

[21]  Kris Thielemans,et al.  Generation of large numbers of dendritic cells in a closed system using Cell Factories. , 2002, Journal of immunological methods.

[22]  H Newman-Gage,et al.  Application of quality assurance practices in processing cells and tissues for transplantation. , 1995, Cell transplantation.

[23]  W W Minuth,et al.  Tissue factory: conceptual design of a modular system for the in vitro generation of functional tissues. , 2004, Tissue engineering.

[24]  R K Wang,et al.  The potential of optical coherence tomography in the engineering of living tissue. , 2004, Physics in medicine and biology.

[25]  S R Burger,et al.  Design and operation of a current good manufacturing practices cell-engineering laboratory. , 2000, Cytotherapy.

[26]  M. Koller,et al.  Clinical-scale human umbilical cord blood cell expansion in a novel automated perfusion culture system , 1998, Bone Marrow Transplantation.

[27]  G. Naughton,et al.  From Lab Bench to Market , 2002 .

[28]  Ram V Devireddy,et al.  Transport phenomena during freezing of adipose tissue derived adult stem cells. , 2005, Biotechnology and bioengineering.

[29]  Juan Jofre,et al.  A method to maintain mammalian cells for days alive at 4 °C , 2004, Cytotechnology.

[30]  Margam Chandrasekaran,et al.  Rapid prototyping in tissue engineering: challenges and potential. , 2004, Trends in biotechnology.

[31]  Hajime Ohgushi,et al.  Viability and osteogenic potential of cryopreserved human bone marrow-derived mesenchymal cells. , 2005, Tissue engineering.

[32]  José Luis Bueno,et al.  A randomized crossover trial comparing three plateletpheresis machines , 2005, Transfusion.

[33]  Naomi Nakagata,et al.  Experimental evaluation of cross-contamination between cryotubes containing mouse 2-cell embryos and murine pathogens in liquid nitrogen tanks. , 2003, Experimental animals.

[34]  A. Goldstone,et al.  Hepatitis B transmission from contaminated cryopreservation tank , 1995, The Lancet.

[35]  Q. Meng,et al.  Hypothermic Preservation of Hepatocytes , 2008, Biotechnology progress.

[36]  R. Roberts,et al.  Low O2 tensions and the prevention of differentiation of hES cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[37]  G. Stephanopoulos,et al.  Metabolic flux analysis: a powerful tool for monitoring tissue function. , 1999, Tissue engineering.

[38]  G C du Moulin,et al.  A 3‐year experience of quality control and quality assurance in the multisite delivery of a lymphocyte‐based cellular therapy for renal cell carcinoma , 1994, Biotechnology and bioengineering.

[39]  N J Titchener-Hooker,et al.  Economic comparison between conventional and disposables-based technology for the production of biopharmaceuticals. , 2001, Biotechnology and bioengineering.

[40]  Mehmet Toner,et al.  Bioartificial liver process monitoring and control systems with integrated systems capability. , 2002, Tissue engineering.

[41]  Boon Chin Heng,et al.  Can the high nuclear to cytoplasmic ratio of human embryonic stem cells make them more vulnerable to physical stress encountered with bulk-passage protocols? , 2005, Medical hypotheses.

[42]  Kimiko Yamamoto,et al.  Fluid shear stress induces differentiation of Flk-1-positive embryonic stem cells into vascular endothelial cells in vitro. , 2005, American journal of physiology. Heart and circulatory physiology.

[43]  P. Lau,et al.  Microbial contamination of embryos and semen during long term banking in liquid nitrogen. , 2003, Cryobiology.

[44]  Jung-Keug Park,et al.  Optimization of cryoprotectants for cryopreservation of rat hepatocyte , 2004, Biotechnology Letters.

[45]  Simon May Strategies for medium-throughput automated genotyping methods. , 2002, Psychiatric genetics.

[46]  Michael V Sefton,et al.  Endotoxin: the uninvited guest. , 2005, Biomaterials.

[47]  J E Prenosil,et al.  Optical waveguide lightmode spectroscopy (OWLS) to monitor cell proliferation quantitatively. , 2002, Biotechnology and bioengineering.

[48]  R. Zimmermann,et al.  Frequently used plateletpheresis techniques result in variable target yields and platelet recruitment of donors , 2005, Transfusion.

[49]  N J London,et al.  Development of an automated computer-controlled islet isolation system. , 1997, Cell transplantation.

[50]  Nick Medcalf,et al.  Functional assessment of tissue-engineered meniscal cartilage by magnetic resonance imaging and spectroscopy. , 2003, Tissue engineering.

[51]  Laura Marcu,et al.  Noninvasive in situ evaluation of osteogenic differentiation by time-resolved laser-induced fluorescence spectroscopy. , 2004, Tissue engineering.

[52]  Barry C Buckland,et al.  The process development challenge for a new vaccine , 2005, Nature Medicine.

[53]  S. Boyce,et al.  Fabrication, quality assurance, and assessment of cultured skin substitutes for treatment of skin wounds , 2004 .

[54]  Chris Mason,et al.  Translational regenerative medicine research: essential to discovery and outcome. , 2007, Regenerative medicine.

[55]  M Taya,et al.  Valuation of growth parameters in monolayer keratinocyte cultures based on a two-dimensional cell placement model. , 2000, Journal of bioscience and bioengineering.

[56]  D Weuster-Botz,et al.  Development, parallelization, and automation of a gas-inducing milliliter-scale bioreactor for high-throughput bioprocess design (HTBD). , 2005, Biotechnology and bioengineering.

[57]  G C du Moulin,et al.  Validation of an automated method of endotoxin testing for use in the end‐product testing of ex vivo activated T‐lymphocytes used in a somatic cell therapy , 2000, Biotechnology and bioengineering.

[58]  Masahiro Kino-Oka,et al.  Bioreactor design for successive culture of anchorage-dependent cells operated in an automated manner. , 2005, Tissue engineering.

[59]  E. Read,et al.  Development of a closed-system process for clinical-scale generation of DCs: evaluation of two monocyte-enrichment methods and two culture containers. , 2002, Cytotherapy.

[60]  I. Safarik,et al.  Use of magnetic techniques for the isolation of cells. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[61]  Gary C. du Moulin,et al.  Overview of a quality assurance/quality control compliance program consistent with FDA regulations and policies for somatic cell and gene therapies: a four year experience , 1994 .

[62]  U A Stock,et al.  ProteinChip system technology: a powerful tool to analyze expression differences in tissue-engineered blood vessels. , 2004, Tissue engineering.

[63]  L. Nielsen,et al.  Bioreactors for hematopoietic cell culture. , 1999, Annual review of biomedical engineering.

[64]  Peter Dunnill,et al.  Behavior of adult human mesenchymal stem cells entrapped in alginate-GRGDY beads. , 2006, Tissue engineering.

[65]  Y H Zhou,et al.  Visualizing integrated bioprocess designs through "windows of operation". , 1999, Biotechnology and bioengineering.

[66]  Adrian P Gee,et al.  Regulatory issues in cellular therapies , 2003, Expert opinion on biological therapy.

[67]  Molly M. Stevens,et al.  Multivariate analysis of Raman spectra for in vitro non-invasive studies of living cells , 2005 .

[68]  Nigel J Titchener-Hooker,et al.  Use of Operating Windows in the Assessment of Integrated Robotic Systems for the Measurement of Bioprocess Kinetics , 2005, Biotechnology progress.

[69]  C. Felten,et al.  Development of a PCR method for mycoplasma testing of Chinese hamster ovary cell cultures used in the manufacture of recombinant therapeutic proteins. , 2004, Biologicals : journal of the International Association of Biological Standardization.

[70]  Gary C du Moulin,et al.  Development of a regulatory strategy for the cellular therapies : an American perspective , 2000 .