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Incidence of mental health diagnoses during the COVID-19 pandemic: a multinational network study
- Yi Chai, Kenneth K. C. Man, Hao Luo, Carmen Olga Torre, Yun Kwok Wing, Joseph F. Hayes, David P. J. Osborn, Wing Chung Chang, Xiaoyu Lin, Can Yin, Esther W. Chan, Ivan C. H. Lam, Stephen Fortin, David M. Kern, Dong Yun Lee, Rae Woong Park, Jae-Won Jang, Jing Li, Sarah Seager, Wallis C. Y. Lau, Ian C. K. Wong
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 33 / 2024
- Published online by Cambridge University Press:
- 04 March 2024, e9
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Aims
Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic.
MethodsBy using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions.
ResultsA total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021.
ConclusionsHealthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.
Contributors
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- By Aakash Agarwala, Linda S. Aglio, Rae M. Allain, Paul D. Allen, Houman Amirfarzan, Yasodananda Kumar Areti, Amit Asopa, Edwin G. Avery, Patricia R. Bachiller, Angela M. Bader, Rana Badr, Sibinka Bajic, David J. Baker, Sheila R. Barnett, Rena Beckerly, Lorenzo Berra, Walter Bethune, Sascha S. Beutler, Tarun Bhalla, Edward A. Bittner, Jonathan D. Bloom, Alina V. Bodas, Lina M. Bolanos-Diaz, Ruma R. Bose, Jan Boublik, John P. Broadnax, Jason C. Brookman, Meredith R. Brooks, Roland Brusseau, Ethan O. Bryson, Linda A. Bulich, Kenji Butterfield, William R. Camann, Denise M. Chan, Theresa S. Chang, Jonathan E. Charnin, Mark Chrostowski, Fred Cobey, Adam B. Collins, Mercedes A. Concepcion, Christopher W. Connor, Bronwyn Cooper, Jeffrey B. Cooper, Martha Cordoba-Amorocho, Stephen B. Corn, Darin J. Correll, Gregory J. Crosby, Lisa J. Crossley, Deborah J. Culley, Tomas Cvrk, Michael N. D'Ambra, Michael Decker, Daniel F. Dedrick, Mark Dershwitz, Francis X. Dillon, Pradeep Dinakar, Alimorad G. Djalali, D. John Doyle, Lambertus Drop, Ian F. Dunn, Theodore E. Dushane, Sunil Eappen, Thomas Edrich, Jesse M. Ehrenfeld, Jason M. Erlich, Lucinda L. Everett, Elliott S. Farber, Khaldoun Faris, Eddy M. Feliz, Massimo Ferrigno, Richard S. Field, Michael G. Fitzsimons, Hugh L. Flanagan Jr., Vladimir Formanek, Amanda A. Fox, John A. Fox, Gyorgy Frendl, Tanja S. Frey, Samuel M. Galvagno Jr., Edward R. Garcia, Jonathan D. Gates, Cosmin Gauran, Brian J. Gelfand, Simon Gelman, Alexander C. Gerhart, Peter Gerner, Omid Ghalambor, Christopher J. Gilligan, Christian D. Gonzalez, Noah E. Gordon, William B. Gormley, Thomas J. Graetz, Wendy L. Gross, Amit Gupta, James P. Hardy, Seetharaman Hariharan, Miriam Harnett, Philip M. Hartigan, Joaquim M. Havens, Bishr Haydar, Stephen O. Heard, James L. Helstrom, David L. Hepner, McCallum R. Hoyt, Robert N. Jamison, Karinne Jervis, Stephanie B. Jones, Swaminathan Karthik, Richard M. Kaufman, Shubjeet Kaur, Lee A. Kearse Jr., John C. Keel, Scott D. Kelley, Albert H. Kim, Amy L. Kim, Grace Y. Kim, Robert J. Klickovich, Robert M. Knapp, Bhavani S. Kodali, Rahul Koka, Alina Lazar, Laura H. Leduc, Stanley Leeson, Lisa R. Leffert, Scott A. LeGrand, Patricio Leyton, J. Lance Lichtor, John Lin, Alvaro A. Macias, Karan Madan, Sohail K. Mahboobi, Devi Mahendran, Christine Mai, Sayeed Malek, S. Rao Mallampati, Thomas J. Mancuso, Ramon Martin, Matthew C. Martinez, J. A. Jeevendra Martyn, Kai Matthes, Tommaso Mauri, Mary Ellen McCann, Shannon S. McKenna, Dennis J. McNicholl, Abdel-Kader Mehio, Thor C. Milland, Tonya L. K. Miller, John D. Mitchell, K. Annette Mizuguchi, Naila Moghul, David R. Moss, Ross J. Musumeci, Naveen Nathan, Ju-Mei Ng, Liem C. Nguyen, Ervant Nishanian, Martina Nowak, Ala Nozari, Michael Nurok, Arti Ori, Rafael A. Ortega, Amy J. Ortman, David Oxman, Arvind Palanisamy, Carlo Pancaro, Lisbeth Lopez Pappas, Benjamin Parish, Samuel Park, Deborah S. Pederson, Beverly K. Philip, James H. Philip, Silvia Pivi, Stephen D. Pratt, Douglas E. Raines, Stephen L. Ratcliff, James P. Rathmell, J. Taylor Reed, Elizabeth M. Rickerson, Selwyn O. Rogers Jr., Thomas M. Romanelli, William H. Rosenblatt, Carl E. Rosow, Edgar L. Ross, J. Victor Ryckman, Mônica M. Sá Rêgo, Nicholas Sadovnikoff, Warren S. Sandberg, Annette Y. Schure, B. Scott Segal, Navil F. Sethna, Swapneel K. Shah, Shaheen F. Shaikh, Fred E. Shapiro, Torin D. Shear, Prem S. Shekar, Stanton K. Shernan, Naomi Shimizu, Douglas C. Shook, Kamal K. Sikka, Pankaj K. Sikka, David A. Silver, Jeffrey H. Silverstein, Emily A. Singer, Ken Solt, Spiro G. Spanakis, Wolfgang Steudel, Matthias Stopfkuchen-Evans, Michael P. Storey, Gary R. Strichartz, Balachundhar Subramaniam, Wariya Sukhupragarn, John Summers, Shine Sun, Eswar Sundar, Sugantha Sundar, Neelakantan Sunder, Faraz Syed, Usha B. Tedrow, Nelson L. Thaemert, George P. Topulos, Lawrence C. Tsen, Richard D. Urman, Charles A. Vacanti, Francis X. Vacanti, Joshua C. Vacanti, Assia Valovska, Ivan T. Valovski, Mary Ann Vann, Susan Vassallo, Anasuya Vasudevan, Kamen V. Vlassakov, Gian Paolo Volpato, Essi M. Vulli, J. Matthias Walz, Jingping Wang, James F. Watkins, Maxwell Weinmann, Sharon L. Wetherall, Mallory Williams, Sarah H. Wiser, Zhiling Xiong, Warren M. Zapol, Jie Zhou
- Edited by Charles Vacanti, Scott Segal, Pankaj Sikka, Richard Urman
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- Essential Clinical Anesthesia
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2 - Equipment
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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- General Techniques of Cell Culture
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Summary
In its broadest definition, equipment includes the laboratory in which cell culture work is undertaken. Some are fortunate enough to occupy purposebuilt cell culture facilities but many use existing laboratories which require varying degrees of adaption to house a successful cell culture area. When planning a laboratory for cell culture, six main functions have to be accommodated. These can be neatly divided into two main groups: sterile handling and support services. Sterile handling includes a cell culture and manipulation area which should be adjacent to an incubation and a storage area. Support services include washing-up, preparation (repackaging) and sterilization. These three functions should also be adjacent to each other and provision made to extract the large amounts of heat and steam associated with this type of operation. It is not essential for the services to be adjacent to the sterile handling area but they should be within the same building. By far the most important consideration is to minimize the chances of microbiological contamination of cell cultures. One of the main causes of contamination can be sudden draughts of room air crossing the work surface from opening doors, the passage of staff behind the operator, open windows or wall-mounted air-conditioning units. Where a laboratory has opening windows, it is vital they are kept closed whenever cell culture work is in operation. Wall–mounted air-conditioning units have no place in a cell culture laboratory because the damp internal conditions harbour and support a source of microbiological contamination readily circulated by the forced movement of air from the unit.
10 - Health and safety
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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Safety is primarily the application of common sense, care and caution. Long before any legislation was introduced, it was fully appreciated that laboratories as workplaces had certain inherent dangers associated with them and, as a result, most persons working in them took care not to endanger themselves. This also meant that other members of staff were comparatively safe and is the main reason why laboratories have always been statistically one of the safest places in which to work. Even today, most laboratories still operate with a philosophy of safety regardless of any introduced legislation.
Instruction in practical safety relating to a specific laboratory should be available from a senior member of the scientific or technical staff and/or from an organizational safety officer where there is one.
The following are a few general guidelines that should be followed wherever practicable when working in a laboratory:
Always wear a laboratory coat (preferably of the newer side-fastening ‘Howie’ type if possible).
Always wear disposable gloves when working. Both coats and gloves should be removed when leaving the laboratory.
Never eat, drink, chew, store food, smoke or apply make-up in the laboratory.
Never use the mouth to fill or discharge pipettes. Always use some form of manual pipette filler.
Hands must be disinfected or washed immediately if contamination is suspected, after handling viable materials and also before leaving the laboratory. Flush eyes and or mucous membrane areas immediately with water if they have come in contact with blood or other viable materials and seek medical assistance.
Perform all procedures so as to minimize spillages and the production of aerosols.
[…]
Glossary
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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3 - Cell culture media
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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Summary
Choice of a suitable culture medium, appropriate for the type of cell it is intended to cultivate, is very important. For established cell lines, the medium used will have been pre-determined and it is then usually only a question of continuing with the same medium, serum and culture conditions. Over the history of cell culture, a large number of different types of medium and balanced salt solutions has been formulated and published but even today the vast majority of cells are cultivated in one of seven or eight different media. The formulations for six of the more popular ones are given in Table 3.1 and discussed in this chapter.
Many of the other formulations were developed specifically for the cultivation of cells with more specialized nutritional requirements, and most commercial suppliers offer a selection of both types of medium. For primary cell cultures, the type of medium used is the choice of the researcher. More often than not, an established cell line can be adapted to grow in an alternative medium should the need arise but, when doing so, cultures should always be run in parallel in order to monitor the comparison until adaption has been assessed to have fully occurred.
Sources
How the researcher obtains their medium will usually depend on the type of organization in which they carry out their research. Centralized in-house production or a Stores stock system will usually mean ready access to medium but, in all other cases, the medium will either have to be purchased directly from a commercial supplier or made in the laboratory.
Acknowledgements
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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Contents
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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- General Techniques of Cell Culture
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Frontmatter
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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8 - Quality control
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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Summary
Guidelines have been given in Chapters 1, 3 and 5 concerning the handling of new cell lines in such a way that the researcher can be assured that the cells are free of contamination, but quality control is not a procedure kept solely for use when new material is received or when primary cultures are set up in the laboratory. The continuous monitoring of cultures and ingredients is essential and requires constant vigilance. Some contaminants are visible to the naked eye but others, e.g. contamination with some strains of mycoplasma are not, and even the effects of such infection may not be immediately obvious, hence the need for constant testing. The importance of carrying out experiments with contaminant-free cells cannot be overstressed (Mowles & Doyle, 1990).
Once contamination is present in a culture, it can easily be spread, so it is necessary that all staff are aware of the potential for problems to occur. However, in some cases the presence of a contaminant may not be such a calamity as it was before the days of mycoplasma removal agents and a wide range of efficient antibiotics.
Many laboratories indulge in the practice of using antibiotics in cell culture as a routine procedure. This leads to the suppression of bacterial contamination which can encourage the spread of antibiotic-resistant strains. Antibiotics can also reduce levels of mycoplasma, making them harder to detect. Microbial quality control is concerned with the testing of cell lines and media for a variety of micro-organisms including bacteria, yeasts, fungi, viruses and mycoplasma.
7 - Cryopreservation
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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Summary
It is quite often the case that particular lines of cells used by a laboratory are not required in culture continuously, but it can be important to have ready access to fresh stocks when required. Cell lines can be purchased direct from national collections but this takes time and could be expensive depending on the number purchased annually. Supplies from fellow researchers in other laboratories may not be readily available and may be of unknown quality. Most laboratories involved in cell culture establish cell banks of their own in liquid nitrogen refrigerators providing instant access when required.
Establishing a cell bank
A cell bank is very simple to set up and requires the following:
a liquid nitrogen refrigerator or −150 °C ultra-low freezer. Liquid nitrogen refrigerators come in varying sizes from small units holding cryotubes to very large units holding many thousands of tubes (see Chapter 2 for details of suppliers);
storage racks and boxes in which to place the tubes;
a regular source of liquid nitrogen;
insulated gloves and a visor;
a supply of cryotubes. These are thick-walled screw-capped polypropylene tubes, specifically designed for liquid nitrogen storage and available in various capacities from 1.0 ml upwards. Never use any other type of plastic tube for this purpose;
a comprehensive and accurate record system for logging every cell line stored in it. This can be either computer based (with or without hard copies) or handwritten in folders.
Index
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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- General Techniques of Cell Culture
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1 - Introduction
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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- General Techniques of Cell Culture
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Summary
The aim of this volume is to provide a guide to the basic essentials of tissue culture, progressing from the equipment needed, through useful media and sera to the handling of different types of cells, their growth and storage, how to recognize and deal with contamination, and to provide some pointers towards good quality control and safe handling procedures. Detailed protocols on specialized applications are outside the scope of this book, although a chapter is included which covers the basics of some of the more widely used special techniques.
Individual volumes in this series deal with the specific cultures of primary cell types, but before commencing on a project necessitating more specialized skills it may be useful to experience the pleasures and pitfalls of basic tissue culture methods, which will be applicable to primary systems, through handling cell lines. Cell banks and smaller cell production facilities exist largely for the purpose of issuing cell lines and during the culturing of a few selected varieties, anyone of average dexterity and with a good grasp of sterile technique will soon develop a basic expertise.
Tissue culture developed from some of the embryology techniques used in the last century, which involved maintaining the medullary plate of a chick embryo in warm saline. Attempts were also made to maintain pieces of human skin in vitro. This was followed by attempts to maintain leukocytes from the salamander in hanging droplets (Jolly, 1903). From this early work, the traditional tissue culture techniques were rapidly devised. The term ‘tissue culture’ includes both cell and organ culture, although within the confines of this book we will be discussing only the former.
6 - Preparation of primary cells
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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A primary culture is one started from cells, tissues or organs which are taken directly from an organism. The term primary applies until the culture is passaged for the first time, when it is called a secondary culture. As emphasized previously, at confluence the primary culture will have its closest resemblance to the parent tissue and, for this reason, early passage cells have the advantage that they will not have had time to become dedifferentiated through continuous growth in vitro and should still retain the properties of the parent material. In the case of some cell types, e.g. avian cells, cultures can not be maintained for more than a few passages so that the preparation of primary cultures is necessary.
Primary cultures are obtained either by disaggregating tissue mechanically, this is used most often for cultures where there is little connective tissue present (Wasley & May, 1970), or with the use of enzymes to produce a cell suspension from which some cells will adhere to a suitable surface, or by allowing cells to grow out from tissue explants.
Different tissues may require specialized techniques (see other books in this series), but there are several requirements that will apply to the preparation of most primary cultures.
Embryonic tissues yield more viable cells and grow more rapidly in culture than adult material.
The number of cells seeded per vessel should be of a much higher concentration than would be used for the subculture of an established cell line, as the proportion of cells from the tissue that will survive may be low.
[…]
General Techniques of Cell Culture
- Maureen A. Harrison, Ian F. Rae
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- Published online:
- 02 February 2010
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- 13 October 1997
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Cell culture techniques are invaluable to the modern researcher but difficult to carry out successfully. As part of the series of Handbooks in Practical Animal Cell Biology, this volume offers a concise practical guide to the basic essentials of the technique. Researchers new to cell culture will find a clear explanation of the essential equipment of a tissue culture facility, including tissue culture media and sera. It describes methods for growing suspension and adhesion cultures, including how to store cells and prepare primary cultures from cells. For those already culturing cells, the handbook will act as a handy reference to the basic techniques. The essence of the book is to deal with the generalities of cell culture to give a grasp of the basic concepts before involvement in more specialized work in the field. Ideal for anyone moving into tissue cell culture techniques or looking for a concise reference book.
9 - Specialized techniques
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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Summary
The main purpose of this book is to provide basic information sufficient for anyone unfamiliar with, or with relatively little experience of, cell culture techniques, to get started and produce comparatively small amounts of cells successfully. In this chapter, an introduction is given to some of the more specialized techniques used in cell culture, including those designed primarily for maximizing the yield of cells or cell product and for immortalizing cells.
Scaling-up
Some techniques are specific to adherent (anchorage–dependent) cells, some to suspension cells, and some can be used for either type.
Specifically for adherent cells
There are various methods available to increase the yield of cells beyond that obtained from the basic culture flask. The main method designed specifically for adherent cells is the use of microcarriers.
Microcarrlers
Microcarriers are minute beads made from various materials available from several suppliers in various sizes and specific gravities (see Table 9.1).
Some microcarriers are solid beads allowing cells to grow only on the outer surface and some are ‘macroporous’ constructed like a sponge where the cells grow not only on the outer surface but within the microcarrier itself greatly increasing the yield (20– to 50–fold). The use of microcarriers enables adherent cells, once attached to the microcarriers, to be grown in a spinner vessel or fermenter as a stirred culture allowing comparatively large numbers of cells to be grown in a relatively small volume of medium. It is possible to recover the cells from the microcarriers by the use of a proteolytic enzyme such as trypsin but not all the cells will be recovered if the macroporous type are used.
5 - Cell culture
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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Summary
As explained in Chapter 1, one of the advantages of cell culture is that it may be used, in many cases, as an alternative technique to the use of live animals for studying models of physiological function in vivo. It is therefore essential that in vitro conditions mimic as closely as possible those that the cell would encounter in vivo. An exact replica of these conditions cannot be achieved, and consequently there will inevitably be changes in cell characteristics. Cell-to-cell interactions are reduced and cells which would not normally proliferate in vivo will do so under in vitro situations. This eventually leads to the growth of unspecialized cells rather than the expression of differentiated functions, which is why it is important to check cell characteristics regularly when cells have been cultured for any length of time. (Further discussion on this and other related factors will be covered in Chapter 8, Quality Control.)
Primary culture techniques are explained in Chapter 6. Once a primary culture has been maintained for some hours, some cell types will proliferate whilst others will survive but not multiply and others will die off. In this way, in the case of monolayer cultures, the distribution of cell types will alter until the cells are confluent, i.e. the cells are touching each other and there is no more substrate space. At confluence, the culture will have its closest resemblance to the parent tissue. After passage or subculture, the primary culture becomes a cell line (now termed a secondary culture) and may be subcultured several more times (but not necessarily established, after a few passages).
4 - Serum
- Maureen A. Harrison, Imperial Cancer Research Fund, London, Ian F. Rae, Imperial Cancer Research Fund, London
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Summary
Since the early days of cell culture technology, serum has been used as an important component in media for growing animal cells. It remains the principal supplement to increase the effectiveness of chemically defined media and contains most, if not all, of the growth factors and hormones that cells require for their growth. It is wide practice to use varying amounts of serum (up to 20%) to make up for small qualitative deficiencies in synthetic media.
Serum-free medium
In the early 1970s it was suggested that serum proteins acted mostly as carriers for low molecular weight hormones or growth factors and, if these could be provided in the medium, the presence of serum would not be necessary. In recent years many excellent serum-free media have been brought on to the market, which have proved this hypothesis. However, these have two disadvantages in the average laboratory set-up: (a) expense and (b) it is apparent that each cell line may require a different set of growth factors and base medium for growth. In a situation where one cell line is being grown on a large scale and deficiencies of particular components may be monitored on a regular basis and compensated for, serum-free media are useful, but where the researcher may be growing different cell lines the convenience of using serum cannot be overestimated.
Most serum-free media may be purchased as a complete package (either in liquid or powder form) and will contain a variety of amino acids, vitamins and inorganic salts plus one or more supplements to replace serum, e.g. bovine serum albumin, transferrin, insulin, epidermal growth factor, bovine pituitary extract, etc.