Tuesday, August 20, 2019
Marketing Mix: Tactical Components To Promote Sales
Marketing Mix: Tactical Components To Promote Sales Carlsberg is also one of the largest brewers in Europe. Moreover, Carlsberg is headquartered in Valby in Copenhagen, Denmark. Carlsberg beer portfolio includes more than 500 brands and they are varies significantly in term of volume, price, target audience and geographic penetration. The companys main brand is Carlsberg Beer but it also brews Tuborg as well too. In January 2001, Carlsberg breweries decided to merge with the Norwegian brewery group Orkla ASA and later Carlsberg has become the fifth largest brewery group in the world. Currently, Povl Krogsgaar-Larsen is the Chairman of the Executive Board of Carlsberg Foundation while Jess Soderberg is the Deputy Chairman of the Executive Board of Carlsberg Foundation. Meanwhile, Flemming Besenbacher is one of the members of the Executive Board of Carlsberg Foundation from 2005 until today. 1.1 History Background Carlsberg was constituted in 1847 by J.C. Jacobsen on a hill at Valby. In order to expand the brand name of Carlsberg, it decided to start its exportation in the year 1868. In 1870, Carlsberg had started to become a very successful brewery and the founder, J.C. Jacobsen wanted to share his business with his country. In 1875, the Carlsberg Research Centre was established to research on scientific problem related to brewing and pioneered the very latest brewing technology and techniques. There are more than 1000 scientists devoted to the art of quality beer manufacturing currently. J.C. Jacobson established the Carlsberg Foundation in 1876. In the year 1906, the Old Carlsberg and New Carlsberg have merged and changed the name to Carlsberg breweries due to the division of production was not viable in the long term. As for today, Carlsberg is the beer for modern young people who speak one language in the world with no boundaries. As for information, the Carlsberg brand also provides support to various contests in the world, such as golf tournaments in Asia and English Liverpool Football Club. Carlsberg has it owns organization target, mission and vision. The mission of Carlsberg Company is to be a dynamic provider of quality beers and its also bring its exciting brand, innovative culture and committed teams which will brings people together and add more enjoyment in life. Furthermore, their companys vision is probably the leading the beer company among the world in order to become the first choice of the consumers, customers and employees and also by fully understanding their needs and proactively driving market development. 2.0 What is Marketing Mix? Marketing mix is a combination of tactical components to promote the sales of a product or service (MarketingTeacher, 2010). The firm can control the marketing mix in order to achieve specific goals within a dynamic marketing environment. Basically, the major marketing decision can be divided into four categories which are known as product, price, promotion and place (also known as 4Ps). Product Product is a complex combination of tangible and intangible attributes that provide satisfaction and benefits to the society such as the good, service and idea (Prentice Hall, 2008). When marketing a product, entrepreneurs need to consider and decide the factors which are quality, design, features, variety, utility, branding, packaging and labeling of a particular product. Carlsberg decided to carry out line extensions to extend its brand names to new forms, colors, sizes, ingredients or flavor of its existing product categories (Prentice Hall, 2008). Carlsberg has produced various types of beers in the market throughout the globe and they also try to launch different flavors of beers as they know that individual has different taste and preference for the beer products. By doing this, Carlsberg can be able to satisfy the consumers needs and wants. These are the popular types of beers of Carlsberg: Carlsberg Elephant Carlsberg Lager Tabor Gold Special Brew Tabor Green Danish Royal Stout Ginseng Carlsberg is made from pale lager malt, bittering hops, aroma hops and Carlsberg bottom fermenting yeast. However, Carlsberg has launched different types of beer which can match with various types of dishes, such as seafood, vegetarian, cheese and others (CarlsbergGroup, 2010). Carlsbergs beer products are considered as the convenience goods in consumer product due to the beer products is considered as an inexpensive item which consumers buy frequently and do not do much comparison with other substitute beer products. So, Carlsberg company will differentiate their beer products, produce quality beers, create nice style and design, wrap with unique packaging and labels in order to distinguish itself with its competitors in the global market, such as Heineken and Tiger. Besides, the raw materials that used to produce the beers are the malted barley, hops, yeast, gluten and water. The quality level is different with its competitors in the market because the type of the raw materials that Carlsberg used is not the same. For example, the ways they planted the hops which is one of the raw ingredients are different, so it will end up with different kind of taste. There are also some safety policies in Carlsberg, each of every branch that brews Carlsberg under license, they need to send every type of beers of its sample for once a month for the tasting panel to test in order to ensure the quality of the products (CarlsbergGroup, 2010). So, Carlsberg can consistently deliver the quality that customers pay for. However, one of the Carlsbergs competitors, Heineken, the company produced Buckler which is one of their beer products that is non-alcoholic. So, Heineken can target those young adults and all the religions in the world to buy its non-alcoholic products. Carlsberg did not produce any non-alcohol drink and it might lose its sales because Heineken targets all the consumers irregardless their religion in order to boost up their sale and competed with Carlsberg. Therefore, Carlsberg should also produce non-alcohol drink in order to compete with its tough competitors, Heineken. 3.1 Packaging In the packaging aspect, Carlsberg company uses aluminium cans and glass bottle which can be recycled. The purpose of the packaging is to protect the product from damage and assist retailers in attracting attention to the product (Prentice Hall, 2008). The diagram below shows the difference between the packaging designs of the Carlsberg Lager. BEFORE AFTER Changes of the packaging design of Carlsberg Lager. By doing this, Carlsberg can create instant consumer recognition of the company or brand. Moreover, by making the packaging design unique, Carlsberg can competes with its competitors and its products packaging can also catch the attention of the consumers even if its products are on the same retail store shelves with other substitute beers. For example, Carlsberg started to use environmentally responsible packaging materials and packaging the Carlsberg lager into a unique style glass bottle and less used of papers on it. However, some elderly customers might not be able to see the words that are curved on the Carlsberg Lagers bottle and end up buying other substitute beers that the words can be see clearly. So, Carlsberg should also pay attention on the minority consumers and improve its packaging to look more outstanding than the other beer brands in the market. 3.2 Labeling Labels can be ranged from simple tags attached to products to complex graphics that are part of the package (Prentice Hall, 2008). Moreover, Carlsberg labels its products might also help to promote its products and also support its positioning. As for information, majority of the consumers will look at the percentage of the alcohol of the beer products and they prefer to buy those beer products contain with high percentage of alcohol. Carlsberg labels their beer products in detail: Carlsberg Special Brew It contains 12kcal of calories, 1.1g of carbohydrates, and 2.6g of alcohol. Carlsberg Lager It contains 12kcl of calories, 1.1g of carbohydrates, and 1.1g of alcohol. Tabor It contains 12kcl of calories, 1.1g of carbohydrates, and 1.4g of alcohol. Carlsberg Elephant It contains 13.75kcl of calories, 1.3g of carbohydrates, and 2.9 g of alcohol. Danish Royal Stout Ginseng It contains 15kcl of calories, 1.1g of carbohydrates, and 0.1g of alcohol. Tabor Gold It contains 12kc of calories, 1.1g of carbohydrates, and 2.3g alcohol. Besides that, Carlsberg ensures that their labels contain all the required information and also stated on its products that young adults who are below the age of 18 could not consume its beer products. 3.3 Branding Branding is important to the company because branding can add value to a product. Consumers prefer to buy goods by viewing the brand of the particular goods in the market. Since 1904, Carlsberg has a strong and well-known brand name in the beer industry. The slogan of Carlsberg is Probably the best lager in the world. Previously, Carlsbergs original logos include the swastika and an elephant. However, the world famous Carlsberg logo was introduced by Thorvald Bindesbell in the year 1904, for the launch of Carlsberg pilsner (Logo Design, 2010). The crown on the logo stands for the companys association with the Royal Danish Court. Pricing Price is the amount of money charged for a product or service (Prentice Hall, 2008). It is important to set a price for a product to create and capture customer values in the market. In Malaysia, the government has an authority to set the price for Carlsbergs products which is banned from Muslim. Several country like Vietnam, Sri Lanka and Malaysia have implemented piecemeal legislation such as banning the advertising on TV for any alcoholic beverages but the alcohol companies still have the right and freedom to promote their products. In addition to duties and excise tax, the government levies a sales tax of 20 per cent on the Carlsbergs beer product. As Carlsberg consumption is consider as price-sensitive, major changes in taxes may have an impact on demand. In Russia, an extreme 200% increase in excise duties on beer was implemented in January 2010, and in July 2009 the Ukraine implemented a significant increase of 94% in beer excise duty (Bloomberg, 2010). Carlsberg has carry out thorough scenario planning for 2010 and subsequent years based on already known and anticipated increases in beer excise duty levels. The scenarios include evaluation of prices, packaging and product mix, regional and national market positions and microeconomic factors such as changes in supply and demand for various input costs. Price list of Carlsberg Products The tables above show the price list of the product of both company according to the types of beers and the size volume of the beers. We have converted the price of each product from the United State Dollar ($) to Ringgit Malaysia (RM). 4.1 Internal and external considerations Every country has different pricing for Carlsbergs beer products. For example, Malaysia is an Islamic country. So, malays are not allowed to consume alcoholic drinks. The price of Carlsberg in Malaysia supposedly to be charged in a lower price compared to non-Islamic country. There are some areas in Malaysia which have duty-free for Carlsberg such as Pulau Langkawi. 4.2 Pricing Strategies Price-Adjustment Strategies Segmented pricing: Segmented pricing is to adjust the price to allow for differences in customers, products or locations (Prentice hall, 2008). Carlsberg company uses location pricing, so the price of Carlsberg can be adjusted and flexible but it depends on different country and even in restaurants. Carlsberg focus their sales in pub, restaurants or clubbing place. For instance, comparing the price of Carlsberg between pub and mini market, it seems obviously that the price of Carlsberg in pub would be relatively higher than mini market because people who go to pub are found to be able to afford it and the area of the pub is considered as high class. Carlsberg implements Everyday low pricing (EDLP) which involves charging a constant everyday low price with few or no temporary price discounts. It usually will have some discounts during the festival seasons like Chinese New Year and Christmas. Besides that, Carlsberg use pricing at or near which is one of the pricing strategies. There are few substitute beer products in the market, so the price of the Carlsbergs products will be the same or slightly different with the other substitute beer products. Thus, it can prevent the happening of the price war between Carlsberg and other beer brands. As for information, the price of Carlsbergs products are cheaper compared to the price of Heinekens product but it is slightly lower than the price of Heinekens product. However, the price of Carlsberg and Tiger are the same regardless the size of the beer or packaging. This will be tough for Carlsberg to boost up its sales due to the price for Carlsberg and Tiger are the same in the market. Carlsberg can increase its sales by improving the quality of the beers and give out free gift whenever consumers purchase a carton of Carlbergs beer products. By giving out free gift or limited edition stuff, it will attract the consumers to buy Carlsbergs beer products rather than buying other substitute beer brands in the market. 5.0 Promotion: Carlsberg is well-known in 105 countries such as Japan, Australia, Africa, China, India, and Malaysia, etc and sold in more than 150 markets. Besides that, Carlsberg has adopted some aggressive promotions around the world to pursuit people consume and aware it. In order to compete with its competitors, promotion must be done in order to increase the reputation, generate sales and profits. There are few strong beer brand eager to compete with Carlsberg since Carlsberg is an international business which have branches all around the world, such as Asia, Europe, and other countries. Promotion tactics for Carlsberg are advertising, public relations, sale promotion and personal selling. Moreover, Carlsberg is creating brand awareness in the public. Its public relations is Carlsberg Hue Zing Education Fund (CEF) which give out Studies Loan to all Malaysian citizens who are enrolled in local or foreign institutions of higher learning hold certificate in UEC, SPM or STPM, or any higher certificate. In the Year 2009, the Carlsberg Hue Zing Education Fund had allocated about RM450, 000 which had aided 31 students in need of financial assistance. By doing this, Malaysia citizens will have a good impression on Carlsberg and tend to consume its beer products due to other beer brands never adopt this strategy to create awareness for their products. Carlsberg was crowned the Grand Prize winner of the 11 annual Chinese New Year greeting advertisement award organized by China Press and Nan yang Siang Pau. It cleverly illustrates the transformation of the Chinese character from Ox to Life by adding the iconic Carlsberg swoosh. Furthermore, Carlsberg also have produced their own bottle opener which had their brand name on stated on it. The Glass Beer which label with the logo and Carlsberg Pilsner is also one of the promotion for Carlsberg in Malaysia. 5.1 Advertising Case 1 The contest open to all non-Muslim residents of Malaysia ONLY. Join the Carlsberg Monaco Promotion Contest now and you could win yourself an all expenses paid holiday on private yacht in Monaco. Buy the Carlberg beers that carry a scratch-to-win sticker , scratch it to get the code and submit the code complete with a slogan I am inspired à ¢Ã¢â ¬Ã ¦. (in 20 words or less) using SMS or via the website. For more informations, terms and conditions , please visit the contests site. Prizes : Grand Prize: 7D/6N all expenses paid holiday on private yacht in Monaco for 4 person Special Prize: 11 x 3D/2N paid holiday and yacht experience in Langkawi for 2 persons Weekly Prize: 15 x iPOD Shuffle (1GB) Contest End : On 25th May 2007 Posted: April 30, 2007 by ContestStation.net in Buy Win Contests As the case 1 above, we can see that in order to increase their sales, Carlsberg create a campaign, which provide scratch-to-win sticker to some Carlsberg beer and the participants are required to provide a slogan with the requirement, free traveling is available if they win in the competition. Meanwhile, Carlsberg can also get some inspiration of Slogan from customers and knows more about their consumers. This will create a win-win situation which both the consumers and Carlsberg gain benefit too. In this case, Carlsberg shows that they take importance on the political environment on Malaysia. Malaysia is an Islamic country and alcoholic drinks is illegal in the past, after few years, the government allowed alcoholic drinks to be imported into Malaysia but with the condition that Islamic people are not allowed to purchased or consumed alcoholic drinks. So, Carlsberg only opened this competition for non-Muslim which they are allowed to purchase alcoholic drinks. This shows that Carlsberg did a research before they conduct this activity in Malaysia. Assuming if Carlsberg ignore the rule and regulations, the government will take action on them, or even banned them from importing the alcoholic drinks to Malaysia. 5.2 Direct Mail Direct Mail is a method of advertising to increase the awareness of what promotion does the company had. It is now being claimed that is the fastest and the most saving cost in order to advertise. Carlsberg company spends money on buying the database to record the customers information, such as income level, race, age, taste and preference. By doing this, mailing to the right consumers to promote Carlsbergs beer products will be much more effective than mailing to those consumers who are not interested in alcoholic drinks. So, Carlsberg can send promotion via email to the customers to inform them about their new beer products and contest. However, one of the problems being faced by Carlsberg is that their name was being used by illegal organization which used their company address to scam people money. As shown in below, one of the consumers received the email which was send by the scammer and the email stated that she won a lottery which up to 650,000.00 Pounds from Carlsberg Beer Carlsberg Malta Company. When she attempted to called the contact number that was provided in the mail, she was shocked to find out that the people ask her to pay a few thousand pounds for the bank transfer fees before she can get the rewards. Date: Sun, 29 Jun 2008 03:27:09 -0600 (MDT) From: Carlsberg Company Promotion [emailprotected] Reply-To: [emailprotected] Subject: You Won 650.000.00 Pounds Sterlings: File For Clam now Carlsberg UK Ltd, Jacobsen House 140 Bridge Street, Northampton, NN1 1PZ ***PROMOTION NOTIFICATION*** Dear Winner, This is to inform you of the Award of Six Hundred and Fifty Thousand Pounds (650,000.00 Pounds) from Carlsberg Beer Carlsberg Malta Company.This Promotion Award is to raise the profile of Carlsberg Beer Carlsberg Malta Products consumers males / females in rural and urban Areas. The online promotions email lists were generated from the World Wide Web. This promotion takes place annually to challenge and to take market share from the popular Dutch import beer. The tactics included live events, local campaigns and general buzz to establish the brand one neighborhood at a time in major urban / rural Areas.Your Email Ref Number falls within our European booklet representatives office in United Kingdom . In view of this, your Award of Six Hundred and Fifty Thousand Pounds Sterlings (650,000.00 Pounds Sterlings) will be released to you by will commence the process to facilitate the release of your funds as soon as you contact him, find below the contact details Mr. Edward Phil Processing Director. Email: [emailprotected] Tel: +44 70457 24289 He will brief you on steps to be taken for due processing and remittance of your prize money. File in for your Claims by Furnishing your Fiduciary Agent the information below. VERIFICATION AND FUNDS RELEASE FORM 1. FULL NAMES:________________ 2. ADDRESS:_________City_________State________Postcode_______Country_____ 3. SEX:________________ 4. AGE:________________ 5. OCCUPATION:________________ 6. TELEPHONE NUMBER:________________ 7. NATIONALITY:____________________ Mode Of Transfer: (Bank to Bank online Transfer) From the management of Carlsberg Company UK we would like to say a big congratulation to you Sincerely, Mrs. Dianne Thompson Online Coordinator, Carlsberg Beer Malta Breweries In this case, Carlsberg should be aware of scam organization in the world and it should start to take actions to solve the serious scamming problems which will harm the company brand name in the future. Carlsberg can publishes through newspaper or via Email that they would never organize any contest which will need the customers to bank in a certain amount of money in order to win prizes. The promotion mix of Carlsberg is not very efficient because it is lacked of public relation. Therefore, if the consumers give any comments or suggestions, Carlsberg can make any adjustment to fulfill the consumer wants and improve their beer products quality in the future. 6.0 Place: Carlsberg company distributes its products throughtout the world. Carlsberg has divided their market into four groups which are Afica and Middle East, Americas, Asia and Europe. There are about 45,000 people are working for Carlsberg Group. Besides that, Carlsbergs products are available in exactly 314 countries all over the world. Furthermore, Carlsberg also has the same distribution channel with Heineken (its competitor) such as the wholesale distribution and retail distribution to distribute their products to the customers. Carlsberg will deliver their products to a combination of convience store or hypermarkers like Tesco or Jusco. Carlsberg does not have any distrbution center like Heineken or Tiger because Carlsberg focus on the retail distribution to distribute their products. Some of the example of the retail distribution are the pubs, clubs or bars. Carlsberg will establish alliance with some of the retail distribution to increase their sales. The market of Carlsberg in Africa is categorized according to the geographical. They made the segmentation into West Africa, Central Africa, Southern Africa, Eastern Africa and also North Africa. The Carlsberg Group has been active in western Africa for many years. In central Africa, currently there are only four markets present in Central Africa which is Gabon, Congo, Cameroon and Equatorial Guinea. In Cameroon, Les Brasseries du Cameroun has been producing Tuborg Gold locally since 1979, along with the range of local brands. Cameroon is a very competitive market compared to the rest of the region, with the consumption of 25 liters per person per year. In December 1969, Carlsberg Brewery Malaysia Berhad began brewing with Carlsberg Green Label beer locally in 1972. The Carlsberg brand had become the part of daily life and it is now the undisputed market leader with more than a 50% share of the Malaysian beer market. Carlsberg Malaysia has aimed to be at the forefront of innovation and quality and always led the market with dynamic product launches and massive consumer campaigns. In 2008, Carlsberg Green Label received Malaysias Gold Most Trusted Brand Award for the ninth consecutive year in the Readers Digest consumer survey. In the same year, Carlsberg Malaysia was also announced as the winner of the 2008 Strongest Winning Culture Award amongst all the Carlsberg Group Company across the world. Furthermore, Carlsberg company plans to enter into the Germanys market. There are about 1300 breweries in Germany which is quite a lot of number compare to other small retails. The Germany beer is known as Carlsberg Deutschland. The Germany beer market has been rather sheltered from the rest of the world because of the German Reinheitsgebot regulation, which dated back to the year of 1516. In 2004, Carlsberg acquires a majority shareholding in Holsten-Brauerei. The market position of Carlsberg in Northern Germany is second, while at the whole Germany is the fifth. As for the distribution part, we suggest that Carlsberg should follow the steps of Heineken and Tiger (its competitors) to open several distribution center in many countries, so that the consumers can be able to consume Carlsbergs beer products at anytime and anywhere. Besides that, Carlsberg should also built some distribution center at the rural area, although the place was not well developed. By doing this, more and more people will start to know Carlsbergs brand name throughout the world regardless in the city or rural area. Stem Cells: History, Properties and Research Stem Cells: History, Properties and Research History Stem cellsà areà cellsà found in all multi cellularà organisms. They are characterized by the ability to renew themselves throughà mitoticà cell division andà differentiateà into a diverse range of specialized cell types. Research in the stem cell field grew out of findings byà Ernest A. McCullochà and James E. Tillà at theà University of Torontoà in the 1960s The two broad types of mammalian stem cells are:à embryonic stem cellsà that are isolated from theà inner cell massà ofà blastocysts, andà adult stem cellsà that are found in adult tissues. In a developingà embryo, stem cells can differentiate into all of the specialized embryonic tissues. In adultà organisms, stem cells andà progenitor cellsà act as a repair system for the body, replenishing specialized cells, but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues. Stem cells can now be grown and transformed into specialized cells with characteristics consistent with cells of various tissues such as muscles or nerves throughà cell culture. Highly plastic adult stem cells from a variety of sources, includingà umbilical cord bloodà andà bone marrow, are routinely used in medical therapies. Embryonicà cell linesà andà autologousà embryonic stem cells generated throughà therapeutic cloningà have also been proposed as promising candidates for future therapies Contents (Jump to) 1à Properties 1.1à Self-renewal 1.2à Potency definitions 1.3à Identification 2à Embryonic 3à Adult 4à Amniotic 5à Induced pluripotent 6à Lineage 7à Treatments 8à Research patents 9à Key research events 10à References Properties The classical definition of a stem cell requires that it possess two properties: Self-renewalà the ability to go through numerousà cyclesà ofà cell divisionà while maintaining the undifferentiated state. Potencyà the capacity toà differentiateà into specialized cell types. In the strictest sense, this requires stem cells to be eitherà totipotentà orà pluripotentà to be able to give rise to any mature cell type, althoughà multipotentà orà unipotentà progenitor cellsà are sometimes referred to as stem cells. Self-renewal Two mechanisms exist to ensure that the stem cell population is maintained: Obligatory asymmetric replicationà a stem cell divides into oneà daughter cellà that is identical to the original stem cell, and another daughter cell that is differentiated Stochastic differentiationà when one stem cell develops into two differentiated daughter cells, another stem cell undergoesà mitosisà and produces two stem cells identical to the original. Potency definitions Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morulas cells are totipotent, able to become all tissues and a placenta. Humanà embryonicà stem cells A: Cell colonies that are not yet differentiated. B:à Nerveà cell Potencyà specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell. Totipotentà (a.k.aà omnipotent) stem cells can differentiate into embryonic and extraembryonic cell types. Such cells can construct a complete, viable, organism.à These cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent. Pluripotentà stem cells are the descendants of totipotent cells and can differentiate into nearly all cells,à i.e. cells derived from any of the threeà germ layers. Multipotentà stem cells can differentiate into a number of cells, but only those of a closely related family of cells. Oligopotentà stem cells can differentiate into only a few cells, such as lymphoid or myeloid stem cells. Unipotentà cells can produce only one cell type, their own,à but have the property of self-renewal which distinguishes them from non-stem cells (e.g. muscle stem cells). Identification The practical definition of a stem cell is the functional definition a cell that has the potential to regenerate tissue over a lifetime. For example, the gold standard test for a bone marrow or hematopoietic stem cell (HSC) is the ability to transplant one cell and save an individual without HSCs. In this case, a stem cell must be able to produce new blood cells and immune cells over a long term, demonstrating potency. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew. Properties of stem cells can be illustratedà in vitro, using methods such asà clonogenic assays, where single cells are characterized by their ability to differentiate and self-renew.à As well, stem cells can be isolated based on a distinctive set of cell surface markers. However,à in vitroà culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar mannerà in vivo. Considerable debate exists whether some proposed adult cell populations are truly stem cells. Embryonic Embryonic stem cell linesà (ES cell lines) are cultures of cells derived from theà epiblastà tissue of theà inner cell massà (ICM) of aà blastocystà or earliermorulaà stage embryos.à A blastocyst is an early stageà embryo-approximately four to five days old in humans and consisting of 50-150 cells. ES cells areà pluripotentà and give rise during development to all derivatives of the three primaryà germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adultà bodyà when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or theà placenta. Nearly all research to date has taken place using mouse embryonic stem cells (mES) or human embryonic stem cells (hES). Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin and require the presence of Leukemia Inhibitory Factor (LIF). Human ES cells are grown on a feeder layer of mouse embryonicà fibroblasts(MEFs) and require the presence of basic Fibroblast Growth Factor (bFGF or FGF-2).à Without optimal culture conditions or genetic manipulation, embryonic stem cells will rapidly differentiate. A human embryonic stem cell is also defined by the presence of several transcription factors and cell surface proteins. The transcription factorsà Oct-4,Nanog, andà Sox2à form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.à The cell surface antigens most commonly used to identify hES cells are the glycolipids SSEA3 and SSEA4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research. After nearly ten years of research,à there are no approved treatments using embryonic stem cells. The first human trial was approved by the US Food Drug Administration in January 2009.à However, as of August 2010, the first human trial had not yet been initiated. Although, The first human medical trial for embryonic stem cells started in Atlanta on October 13, 2010 for spinal injury victims. ES cells, being pluripotent cells, require specific signals for correct differentiation if injected directly into another body, ES cells will differentiate into many different types of cells, causing aà teratoma. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face.à Many nations currently haveà moratoriaà on either ES cell research or the production of new ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a the oretically potential source forà regenerative medicineà and tissue replacement after injury or disease. Adult Also known asà somatic stem cells andà germlineà (giving rise to gametes) stem cells, they can be found in children, as well as adults. Stem cell division and differentiation.à A stem cell; B progenitor cell; C differentiated cell; 1 symmetric stem cell division; 2 asymmetric stem cell division; 3 progenitor division; 4 terminal differentiation Pluripotent adult stem cells are rare and generally small in number but can be found in a number of tissues including umbilical cord blood.à A great deal of adult stem cell research has focused on clarifying their capacity to divide or self-renew indefinitely and their differentiation potential.à In mice, pluripotent stem cells are directly generated from adult fibroblast cultures. Unfortunately, many mice dont live long with stem cell organs. Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell,endothelial stem cell, etc.). Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants.à Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses. The use of adult stem cells in research and therapy is not asà controversialà asà embryonic stem cells, because the production of adult stem cells does not require the destruction of anà embryo. Additionally, because in some instances adult stem cells can be obtained from the intended recipient, (anà autograft) the risk of rejection is essentially non-existent in these situations. Consequently, more US government funding is being provided for adult stem cell research. An extremely rich source for adult mesenchymal stem cells is the developing tooth bud of the mandibular third molar. While considered multipotent they may prove to be pluripotent. The stem cells eventually form enamel (ectodrm), dentin,periodontal ligament, blood vessels, dental pulp, nervous tissues, including a minimum of 29 different unique end organs. Because of extreme ease in collection at 8-10 years of age before calcification and minimal to no morbidity will probably constitute a major source for personal banking, research and multiple therapies. These stem cells have been shown capable of producing hepatocytes. Amniotic Multipotent stem cells are also found inà amniotic fluid. These stem cells are very active, expand extensively without feeders and are not tumorigenic.à Amniotic stem cellsà are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines.à All over the world, universities and research institutes are studyingà amniotic fluidà to discover all the qualities of amniotic stem cells, and scientists such asà Anthony Atalaà andà Giuseppe Simonià have discovered important results. From an ethical point of view, stem cells fromà amniotic fluidà can solve a lot of problems, because its possible to catch amniotic stem cells without destroying embryos. For example, the Vatican newspaper Osservatore Romano called amniotic stem cell the future of medicine. Its possible to collect amniotic stem cells for donors or for autologuous use: the first US amniotic stem cells bankà opened in Medford, MA, byà Biocell Centerà Corporationà à and collaborates with various hospitals and universities all over the world Induced pluripotent These are not adult stem cells, but rather reprogrammed cells (e.g. epithelial cells) given pluripotent capabilities. Using genetic reprogramming with proteinà transcription factors, pluripotent stem cells equivalent toà embryonic stem cellsà have been derived from human adult skin tissue.à Shinya Yamanakaà and his colleagues atà Kyoto Universityà used the transcription factors Oct3/4, Sox2, c-Myc, and Klf4à in their experiments on cells from human faces.à Junying Yu,à James Thomson, and their colleagues at theà University of Wisconsin-Madisonà used a different set of factors, Oct4, Sox2, Nanog and Lin28,à and carried out their experiments using cells from humanà foreskin. As a result of the success of these experiments,à Ian Wilmut, who helped create the first cloned animalà Dolly the Sheep, has announced that he will abandonà nuclear transferà as an avenue of research. Frozen blood samples can be used as a source of induced pluripotent stem cells, opening a new avenue for obtaining the valued cells. Lineage They ensure self-renewal, stem cells undergo two types of cell division (seeà Stem cell division and differentiationà diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and aà progenitor cellà with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminallyà differentiatingà into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such asà receptors) between the daughter cells. An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies inà Drosophilaà germarium have identified the signals dpp and adherens junctions that prevent germarium stem cells from differentiating. Main article:à Induced Pluripotent Stem Cell The signals that lead to reprogramming of cells to an embryonic-like state are also being investigated. These signal pathways include severalà transcription factorsà including theà oncogeneà c-Myc. Initial studies indicate that transformation of mice cells with a combination of these anti-differentiation signals can reverse differentiation and may allow adult cells to become pluripotent. However, the need to transform these cells with an oncogene may prevent the use of this approach in therapy. Challenging the terminal nature of cellular differentiation and the integrity of lineage commitment, it was recently determined that the somatic expression of combinedà transcription factorsà can directly induce other defined somatic cell fates; researchers identified three neural-lineage-specific transcription factors that could directly convert mouseà fibroblastsà (skin cells) into fully-functionalà neurons. This induced neurons (iN) cell research inspires the researchers to induce other cell types implies thatà allà cells areà totipotent: with the proper tools, all cells may form all kinds of tissue. Treatments Medical researchers believe that stem cell therapy has the potential to dramatically change the treatment of human disease. A number of adult stem cell therapies already exist, particularlyà bone marrow transplantsà that are used to treatà leukemia.à In the future, medical researchers anticipate being able to use technologies derived from stem cell research to treat a wider variety of diseases includingà cancer, Parkinsons disease,à spinal cord injuries,à Amyotrophic lateral sclerosis,à multiple sclerosis, andà muscleà damage, amongst a number of other impairments and conditions.à However, there still exists a great deal of social and scientific uncertainty surrounding stem cell research, which could possibly be overcome through public debate and future research, and further education of the public. One concern of treatment is the possible risk that transplanted stem cells could form tumors and have the possibility of becoming cancerous if cell division continues uncontrollably. Stem cells, however, are already studied extensively. While some scientists are hesitant to associate the therapeutic potential of stem cells as the first goal of the research, they find the investigation of stem cells as a goal worthy in itself. Contrarily, supporters of embryonic stem cell research argue that such research should be pursued because the resultant treatments could have significant medical potential. It is also noted that excess embryos created forà in vitro fertilizationà could be donated with consent and used for the research Diseases and conditions where stem cell treatment is promising or emerging.à Bone marrow transplantation is, as of 2009, the only established use of stem cells. Research patents Theà patentsà covering a lot of work on human embryonic stem cells are owned by theà Wisconsin Alumni Research Foundationà (WARF). WARF does not charge academics to study human stem cells but does charge commercial users. WARF soldà Geron Corp.à exclusive rights to work on human stem cells but later sued Geron Corp. to recover some of the previously sold rights. The two sides agreed that Geron Corp. would keep the rights to only three cell types. In 2001, WARF came under public pressure to widen access to human stem-cell technology. These patents are now in doubt as a request for reviewing theà US Patent and Trademark Officeà has been filed by non-profit patent-watchdogsà The Foundation for Taxpayer Consumer Rights, and theà Public Patent Foundationà as well as molecular biologist Jeanne Loring of the Burnham Institute. According to them, two of the patents granted to WARF are invalid because they cover a technique published in 1993 for which a patent had already been granted to an Australian researcher. Another part of the challenge states that these techniques, developed byà James A. Thomson, are rendered obvious by a 1990 paper and two textbooks. The outcome of this legal challenge is particularly relevant to the Geron Corp. as it can only license patents that are upheld. Key research events January 2008à Robert Lanza and colleagues at Advanced Cell Technology and UCSF create the first human embryonic stem cells without destruction of the embryo January 2008à Development of human cloned blastocysts followingà somatic cell nuclear transferà with adult fibroblasts. February 2008à Generation of pluripotent stem cells from adult mouse liver and stomach: these iPS cells seem to be more similar to embryonic stem cells than the previously developed iPS cells and not tumorigenic, moreover genes that are required for iPS cells do not need to be inserted into specific sites, which encourages the development of non-viral reprogramming techniques. March 2008 The first published study of successful cartilage regeneration in the human knee using autologous adult mesenchymal stem cells is published by clinicians from Regenerative Sciences. October 2008à Sabine Conrad and colleagues at Tà ¼bingen, Germany generateà pluripotent stem cellsà from spermatogonial cells of adult human testis by culturing the cells in vitro underà leukemia inhibitory factorà (LIF) supplementation. 30 October 2008à Embryonic-like stem cells from a single human hair. 1 March 2009à Andras Nagy, Keisuke Kaji,à et al.à discover a way to produce embryonic-like stem cells from normal adult cells by using a novel wrapping procedure to deliver specific genes to adult cells to reprogram them into stem cells without the risks of using a virus to make the change. The use ofà electroporationà is said to allow for the temporary insertion of genes into the cell. 28 May 2009à Kimà et al.à announced that they had devised a way to manipulate skin cells to create patient specific induced pluripotent stem cells (iPS), claiming it to be the ultimate stem cell solution. 11 October 2010à First trial of embryonic stem cells in humans References Becker AJ, McCulloch EA, Till JE (1963). Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells.à Siminovitch L, McCulloch EA, Till JE (1963). The distribution of colony-forming cells among spleen colonies.à Journal of Cellular and Comparative Physiology. Tuch BE (2006). Stem cells-a clinical update.à Australian Family Physician. Hans R. Schà ¶ler (2007). The Potential of Stem Cells: An Inventory. In Nikolaus Knoepffler, Dagmar Schipanski, and Stefan Lorenz Sorgner.à Humanbiotechnology as Social Challenge. Ashgate Publishing, Ltd. Mitalipov S, Wolf D (2009).à HYPERLINK http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrezartid=2752493Totipotency, pluripotency and nuclear reprogrammingHYPERLINK http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrezartid=2752493.à Adv Biochem Eng Biotechnolà Ulloa-Montoya F, Verfaillie CM, Hu WS (Jul 2005). Culture systems for pluripotent stem cells.à J Biosci Bioeng.à Friedenstein AJ, Deriglasova UF, Kulagina NN, Panasuk AF, Rudakowa SF, Luria EA, Ruadkow IA (1974). Precursors for fibroblasts in different populations of hematopoietic cells as detected by theà in vitroà colony assay method.Ã
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