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Developing Technical Skills for Stem-Cell Research ADVERTISEMENT FEATURE NATUREJOBS SPOTLIGHT ON STEM-CELL RESEARCH Developing technical skills for stem-cell research Interested in working with stem cells? Find out what it takes to succeed in this dynamic field. HOW IS SPOTLIGHT ON STEM-CELL RESEARCH SPOTLIGHT a stem cell like an orchid? Both are difcult to grow, says leading stem-cell researcher Stephen Minger. To succeed in “More and more people culturing stem cells, you need to have “a green thumb”, he KING’S COLLEGE LONDON in my lab know at least says, and “a mindset of getting inside cells and fguring out what how to write a few they need. It’s something that takes dedication and passion.” lines of program.” Minger’s take on stem-cell research has brought him to the Didier Trono, École Polytechnique role of global head of research and Fédérale de Lausanne development of cell technologies at GE Healthcare Life Sciences, but there are many ways to make a mark. Knowing how to culture stem cells and derive specialized cell types is one of the most important skills in the feld, and Researchers working on stem cells for clinical use, such as this scientist at King’s there are many valuable supporting College London School of Medicine, must abide by strict protocols. roles. Stem-cell investigators arm themselves with a diverse range of techniques to stay at the cutting edge of science. So where Institute in Sweden gave a patient used technique to deliver genes should you focus your eforts? a new trachea made from a 3-D into stem cells uses viral vectors scafold seeded with his own stem such as lentiviruses. “Tey're really Nurturing growth cells. NCS’s Glover suggests that workhorses of stem-cell research,” Te optimal growth media for organ printing — using inkjet says Didier Trono, professor and culturing stem cells is constantly printers to deposit cells into specifc dean at the School of Life Sciences being refned. “In recent years, 3-D patterns — might prove useful at École Polytechnique Fédérale de scientists have been trying to for stem-cell researchers in the Lausanne (EPFL) in Switzerland. mimic the natural environments future. Lorenz Studer, director of Working with viral vectors in of stem cells," says Joel Glover, the Center for Stem Cell Biology at the lab may require an enhanced director of the Norwegian Center Memorial Sloan–Kettering Cancer biosafety level — recombinant for Stem Cell Research (NCS). Center (MSKCC) in New York is lentiviruses can be hazardous — One example of this approach optimistic about the technology’s so experience with the relevant is using exotic gas mixtures to potential. He predicts that as more protocols is advantageous. reproduce the hypoxic conditions scientists study how stem cells Epigenetics — the study of in which many stem cells develop; behave in a 3-D context, knowledge heritable changes in gene function another method involves refning of 3-D imaging techniques such as not involving changes in DNA which growth factors to use two-photon excitation microscopy — is of growing importance in and when to apply them. will become increasingly valuable. stem-cell research. Researchers Another area attracting a lot of are trying to determine how attention is 3-D scafolding. An The role of genetics epigenetic changes infuence cell encouraging application of this A major proportion of stem-cell diferentiation, tissue homeostasis technology was shown in 2011 research involves the genetic and the cell’s response to external when researchers at the Karolinska modifcation of cells. A commonly signals. Familiarity with new | NATUREJOBS | 31 MAY 2012 | 31 MAY | NATUREJOBS 2 ADVERTISEMENT FEATURE US stem-cell research funding Top 10 stem-cell research projects funded by US National Institutes of Health (NIH) in 2011 Project name Recipient organisation Amount (US$) NATUREJOBS Cell therapy for diabetic peripheral neurovascular complications Emory University $6.1m Global annotation of regulatory elements in the human genome Hudson-Alpha Institute for Biotechnology $4.1m KOMP phase II mouse production and cryopreservation University of California Davis $4.0m Research on inhalation toxicology of environmental chemicals Alion Science and Technology Corporation $3.9m Causal transcriptional consequences of human genetic variation Harvard University (Medical School) $3.8m Adult stem cells for therapy of visual disorders Scripps Research Institute $3.8m Center for Cell Circuits Broad Institute $3.7m Growth control in multiple myeloma University of Arkansas for Medical Sciences $3.7m Blood & Marrow Transplant Clinical Trials Network Data Coordinating Center Medical College of Wisconsin $3.5m Transcriptional functions of nuclear receptors in cancer cells NIH $3.4m Mechanisms and biological consequences of the nuclear receptor CAR activation NIH $3.3m Source: NIH SPOTLIGHT ON STEM-CELL RESEARCH SPOTLIGHT researchers at Stanford University to study the adult brain’s neural School of Medicine and their stem cells, while scientists at the colleagues in May 2011, uses Université Libre de Bruxelles in antibodies tagged with various Belgium demonstrated that the isotopes of rare-earth metals mammary gland contains diferent instead of fuorescent molecules. types of long-lived stem cells, a STEMCELL TECHNOLOGIES INC Te cells are vaporized and their fnding that could help unravel constituent parts analyzed by a the cause of breast cancers. On mass spectrometer. Tis approach the other side of the Atlantic, allows scientists to simultaneously researchers at the Stanford measure dozens of features located Institute for Stem Cell Biology on the surface and inside cells, and Regenerative Medicine in whereas conventional fuorescence- California have found that human based fow cytometry can only induced pluripotent stem cells measure a few features at a time. (iPSCs) can be used to model It’s a relatively new but signifcant cardiovascular disease and a team Biotechnology company Stemcell Technologies' research facility in Vancouver, Canada. addition to a stem-cell researcher’s at the Yale Stem Cell Center in toolbox, says Keith March, director Connecticut are using iPSCs of the Indiana Center for Vascular to model the efect of hepatitis Biology and Medicine (ICVBM). B and C infection on human technology will be needed to can be deceiving in stem-cell Knowledge of animal physiology hepatocytes in a mouse host. fnd the answers. “Te arrival research. It’s necessary to study a can be benefcial in understanding Scientists at the New York of high-throughput techniques cell’s function as well as its form. the behaviour of stem cells Stem Cell Foundation have for analyzing epigenetics has “You have to look at more than and derived cells in living generated pluripotent stem helped usher in a revolution in just the morphology and markers organisms. “If you engraf the cells by adding adult nuclei to the feld," says Trono. Epigenetics of a cell,” says Glover of NCS. cells, techniques such as contrast- unfertilized oocytes, a strategy technologies include ChIP-on- “For instance, you can take adult enhanced ultrasound or positron that could help develop patient- chip, which combines chromatin stem cells and [make] them look emission tomography (PET) specifc stem cells for transplants immunoprecipitation (ChIP) like neurons, but they just don't imaging can help you monitor that would not be rejected by with microarray technology, do anything neurons do. You how they integrate,” adds March. the patient's immune system. and ChIP-seq, which combines need additional careful functional Experience of surgery, animal Scientists working with clinical- ChIP with sequencing of the analysis of derived cells, such behaviour and systems biology grade stem cells must adhere to resulting DNA fragments. as of their electrophysiology or can all help assess the broader good manufacturing practices their pattern of hormone release.” implications of stem-cell research. (GMPs) and employ good clinical Sorting and studying Image cytometry also helps practices (GCPs) — regulations Once stem cells are prepared researchers analyze how proteins Into the clinic regarding what is allowed to go and cultured, sorting them of interest are expressed in cells, A major goal for stem-cell into the human body. “Everything into purifed populations via as does confocal microscopy. researchers is to turn basic science has to be traceable — you must techniques such as fow cytometry A process called mass cytometry into clinical therapies. Eforts be sure that no reagent has — identifying cells using — a variation on fow cytometry in this direction are ramping up expired or been kept at the wrong fuorescent-tagged antibodies — is — ofers researchers a novel way across the globe. Te Lund Stem temperature, that everything a crucial skill. But sorting alone to analyze the characteristics of Cell Center in Sweden recently was sterile, and that you have doesn’t guarantee fnding what a population of stem cells. Te established a lab dedicated to stem written evidence this is correct,” you’re looking for; appearances technique, frst described by cells and restorative neurology says Dusko Ilic, senior lecturer in ❯❯ | NATUREJOBS | 31 MAY 2012 | 31 MAY | NATUREJOBS 3 ADVERTISEMENT FEATURE stem-cell science at King’s College “It's extremely challenging — to be resourceful, creative and cell characterization and London School of Medicine in we're working on inherently good at troubleshooting to develop bioinformatics analysis to “entire the United Kingdom. “All work unstable biological entities.” a technique, and have good preclinical studies”, says ICVBM’s NATUREJOBS has to be done by two people; knowledge of the biology of cells March. Collaborations with other you both have to witness and sign Technically minded and cell types,” says Terry Tomas, research groups can also help forms. And there are government As in many felds of biology, senior vice-president of research provide GMP and GCP services. inspections checking that we are advances in high-throughput and development at Stemcell Te fast pace of discovery complying with conditions.” techniques that generate massive Technologies’ headquarters in stem-cell research gives a To follow GMPs you need data sets mean experience in in Vancouver, Canada.
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