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BIOTECH Basics Stem Cells

Introduction What you need to know: Embryonic stem cells develop in an ear- Stem cells: perhaps no other subject ly from specialized cells called the nStem cells can differentiate into many kinds of cells. in medical research has stirred as much inner mass. These ICM cells are plu- passion and controversy. Ethical issues ripotent, meaning they can form all of the nAlternatively, they may continue to surrounding certain aspects of cells in the organism’s body. Embryonic divide and produce more stem cells. research give rise to very personal views. stem cells originate from ICM cells. The nStem cells that occur naturally are However, an understanding of scientific cells are transferred into a petri dish con- embryonic or adult in type. details and medical implications can be taining a nutrient-rich broth and allowed nInduced pluripotent stem cells are an important part of forming and express- to grow and spread across the dish. Once differentiated cells that have been ing opinions. This edition of Biotech Basics these cells are established, subsets can be genetically reprogrammed to behave attempts to provide that understanding, frozen and shipped to other laboratories for like embryonic stem cells. laying the groundwork for discussions con- further study. Nearly all human embryonic nStem cells have the potential to cerning stem cells. stem cells currently in use are derived from shed light on human disease, screen What are stem cells? fertilized at an fertilization potential drugs and replace damaged/ clinic and donated for research purposes. Stem cells serve to help the body re- missing cells in the body. Based on research to date, embryonic place cells lost through aging, damage or nA number of technical and ethical stem cells offer the widest range of devel- other daily activities. There are two key hurdles must be overcome before stem characteristics that distinguish stem cells opmental potential and are the easiest to cells routinely enter clinical practice. from other cell types. culture in the lab. • Potency – Stem cells do not have any Adult stem cells are found inside a tis- sue or organ and are capable of forming If you want to know more: of the tissue-specific structures that allow them to carry out specialized the cells needed by that tissue. They are http://www.cdb.riken.jp/en/05_ functions. Stem cells cannot carry oxy- maintained throughout the life of the organ- development/0505_stemcells04.html gen through the bloodstream, trans- ism and have been identified, among other Stem Cells: Building and Maintaining the tissues, in , marrow, skeletal Body – Riken Center for Developmental mit electrical signals in the nervous muscle, , heart and intestines. Present – a thorough overview of the basics system or produce enzymes to break on stem cells, including the differences down food. However, a stem cell has in very small numbers, adult stem cells are between embryonic and adult stem cells, the ability to develop into blood, multipotent, meaning they can develop into as well as research on how to differentiate and stomach cells. This process of only a few cell types. For example, hema- embryonic stem cells for clinical uses. forming mature cells is called differen- topoietic stem cells, can form red and white http://www.nature.com/scitable/ tiation and is guided by a number of blood cells, as well as the platelets. These spotlight/stem-cells-6969855 key chemical signals and developmen- stem cells can be found in , as Spotlight on Stem Cells – Scitable, by tal stages. well as in the blood obtained from the um- Nature Education – a host of articles and • Self-renewal - Stem cells can renew bilical cord after birth. Notably, banking this web links addressing stem cell biology, umbilical provides a population manufacturing, application and regulation themselves through repeated cycles of while remaining in an of stem cells that can be used to treat cer- http://stemcells.nih.gov/info/basics/ undifferentiated state. This provides tain blood-based diseases that may form defaultpage.asp a continual pool of stem cells that can later in life. Other examples Stem Cell Basics – The National Institutes include mesenchymal stem cells that form of Health – a thorough introduction to stem differentiate as required. bone, and connective tissue, cells, including information regarding U.S. What types of stem cells have been and neural stem cells that can develop policy as it relates to public funding of stem identified? cell research into and other cells found in the

4 . In addition to a reduced – a strategy set of differentiated outcomes, adult stem called directed Figure two: cells are harder to culture and maintain in differentiation. In a laboratory setting when compared to em- many cases, this bryonic stem cells. involves activat- In 2006, scientists discovered tech- ing or silencing niques to genetically reprogram differenti- specific . ated cells into an -like In other instanc- state, giving rise to a third category, in- es it requires duced pluripotent stem cells. These cells the addition of may ultimately offer a widely available specific growth and non-controversial source of pluripo- factors or small tent cells; however, recent studies indi- molecules. Seri- cate that iPSCs and embryonic stem cells ous challenges are similar but not identical. It is likely that still remain: Even embryonic, adult and induced pluripotent in best-case stem cells will each be suited for specific scenarios, less Image credit: The Promise of Stem Cell Research – National Institute of Health research and clinical needs, but will not be than 30 percent - http://stemcells.nih.gov/info/media/promise.htm interchangeable across every application. of the stem cells achieve the de- How might stem cells be used in the of the heart. Similarly, sired cell fate. Even so, the potential for lab and clinic? produced cells from iPSCs of patients directed differentiation opens a number of with liver diseases. The cells mimicked clini- Researchers are beginning to under- clinical and research-based stem cell op- cal features of the disorder. stand the process of portunities (figure 2). Pharmacological testing and the stages that guide a cell into a spe- Modeling human disease cific developmental fate. This knowledge In addition to studies modeling human Understanding how genetic variation has been used in the laboratory to coax disease, differentiated stem cells may be impacts disease is a long-standing goal pluripotent stem cells into mature cell types used to screen large numbers of candidate for human genetics. molecules to speed drug discovery. In both Stem cell analyses, Figure one: the long QT and liver disease studies report- particularly those in- ed above, the differentiated cells tested the volving iPSCs created effects of both existing and potential drugs from patients, can be – an important first step in identifying new used to model human . diseases and com- pare how changes at Replacement cells the DNA level impact An exciting potential application for hu- cell function. This will man stem cells is creating replacement cells. prove especially use- While can replace ful as directed differ- damaged or diseased tissues, the need far entiation creates those outstrips the availability of donor organs. cell types implicated in Stem cells, placed under directed differen- the disease. For ex- tiation, could provide a renewable source of ample, a recent study cardiac muscle cells for failing hearts, do- generated iPSCs from pamine-producing neurons for patients with patients with long QT Parkinson disease or insulin-producing pan- syndrome (an inher- creatic cells for those with Type 1 . ited heart condition) Potentially, any disorder caused by the de- Stem cells vary in their differentiation ability (figure 1). Some are totipo- who had mutations in tent, meaning they can differentiate into any of the cells in the organism’s struction and loss of certain cell types could body, as well as the , and amniotic sac. Pluripo- a specific . The be a candidate for replacement . tent stem cells can only develop into body cells while multipotent stem iPSCs were differ- There are important safety caveats for hu- cells form only subsets of body cells, such as those found in the blood entiated into cardiac man stem cell therapy. Scientists do not yet and lymph system. Once cells have fully differentiated, they can only divide into the same type of differentiated cell: for example, skin cells muscle cells that be- have full control over how the cells grow and only divide and form similar skin cells. Image credit: Wikimedia com- haved as if they were develop. Because of their pluripotent ability, mons – modified from an image created by Mike Jones - http://commons. from various regions it is possible that implanted stem cells will wikimedia.org/wiki/File:Stem_cells_diagram.png Continued on page 6: THE OF PROGRESS 5 :Continued from page 5 • addressing ethical concerns surrounding the creation and uti- form tumors instead of the desired organ or tissue. Cautious and lization of embryonic stem cells. rigorous clinical testing, while potentially frustrating patients and With respect to the last challenge, it is worth noting that Advanced their families, will be the norm for the next several years. Cell Technology, Inc. has developed a technique that obtains a single What are the challenges and concerns embryonic cell without destroying the embryo. This method is similar involving stem cells? to that used in preimplantation genetic diagnosis, where a single cell Historically, stem cell technologies have often been accompa- is obtained for from a four to eight cell embryo. ACT nied with unrealistic hype and promises of imminent clinical utility. says the procedure produces embryonic stem cells identical to those While impressive progress has been made in stem cell research derived from the of a later-stage embryo. and application during the past decade, significant hurdles still Links to HudsonAlpha remain before stem cell therapies become a routine part of the Southern Cord, a private cord blood banking service, is one of clinical landscape. These include: the newest associate companies to locate at HudsonAlpha. As men- • obtaining a full understanding of the pro- tioned above, following the birth of a child, the blood found in the cess for creating pluripotent stem cells; umbilical cord and placenta contains a number of adult stem cells • determining whether iPSCs are a safe and useful stem cell capable of forming the differentiated blood and immune cells. Close alternative; to 80 diseases and disorders including , blood disorders, • identifying the methodology required for predictable direct- hemoglobinopathies and immunodeficiencies are currently treatable ed differentiation; with stem cells obtained from cord blood. • converting research-based protocols into more efficient, reproducible procedures; – Dr. Neil Lamb • developing techniques to improve the growth and culturing director of educational outreach of adult stem cells; HudsonAlpha Institute for Spring Benefit reception a success Hundreds attend make up event after tornadoes

Thanks to everyone who attended the Hud- disease research through this event but were sonAlpha reception highlighting research on unable to attend. View dozens of reception psychiatric disorders on May 19. More than photos on the HudsonAlpha Facebook 250 guests were on hand for the event, which page. was held in lieu of the Spring Benefit for Re- search on Psychiatric Disorders. The original Lower left: HudsonAlpha co-founder benefit was scheduled for April 28, but the Lonnie McMillian with major institute event was canceled after tornadoes ripped supporter Linda Smith of Smith through Alabama, impacting so many in our Asset Management. Right: Carter Wells, director area. of external affairs, addressed The reception maintained the original focus the more than 250 guests of the benefit - psychiatric research underway who attended the benefit at HudsonAlpha. Proceeds from the event reception. support current and future research into major depressive disorder, schizophrenia and SPRING BENEFIT SPONSORS bipolar disorder. Jim Hudson pre- Genome Sponsors Premier Sponsors, Friends of the Institute Sponsors, continued: sented special gifts ADTRAN continued: Cindy and Richard Jackson Jerry Damson Honda Acura to Linda Smith of Smith Asset Management Richard Saperstein & David D’Amico of Treasury Partners Kailos Genetics Smith Asset Manage- Kord Technologies Research Sponsor Irma and Jack Tuder ment and Mike Fo- Lockheed Martin Maynard Cooper & Gale PC liano of ADTRAN as Friends of the Institute Sponsors LUCAS, plc Anglin Reichmann Snellgrove & Armstrong Pearce Construction the event’s Genome DNA Sponsor Kelli and Brian Pollock Sponsors. Corporate Intergraph P.C. AT&T Alabama Redstone Federal Credit Union and individual spon- Bradley Arant Boult Cummings LLP BBVA Compass Regions Bank sors of all levels also Merrill Lynch BlueCross BlueShield of Alabama Renasant Bank received tokens of CFD Research Corporation Emily and Steve Robertson Premier Sponsors Russel Hill Foundation appreciation. Event Conversant Bio BlueCreek Investment Partners Diatherix Laboratories S3, Inc. sponsors are listed Burger King/Wesfam Restaurants, Inc. First Commercial Bank Samples Properties at right. P. Michael Cole, Attorney at Law FPH Benefits LLC Serina Therapeutics Thanks again to COLSA Corporation Fuqua & Partners Architects Teledyne Brown Engineering Toyota Motor Manufacturing Alabama, Inc. all who attended the DESE Research, Inc. Gray Research, Inc. Huntsville Hospital Van Valkenburgh & Wilkinson REALTORS® reception, as well as Lanier Ford Law Firm Sue and Andy Whitehead NEKTAR iCubate those who provided Intuitive Research and Technology Jill and Danny Windham support to psychiatric Northrop Grumman

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