Embryonic stem cells in diabetes therapy

Beta cells transplantation seems the most promising therapy for diabetes, because other current treatments loss their favorable advantage and can not avoid serious adverse effects, such as hyperglycemia. Embryonic stem cells are the ideal biological tool to achieve the complete restoring of pancreatic islet. Current research on diabetes is focused on the identification of a protocol to culture cells. Indeed, embryonic stem cells must be differentiated in order to produce insulin. It has been recently published that high concentration of exendin 4 are able to induce insulin synthesis and differentiation to pancreatic cells. This strategy is a modification of the original protocol that requires the simultaneous administration of exedin 4, nicotinamide and activin b. Additional culturing in low glucose medium seems to further improve embryonic cells differentiation. Despite previous studies, Hu and coworkers (Acta Pharmacologica Sinica) obtained more insulin 1 and peptide C. This study gives great hope to patients that suffer for diabetes and can not have a benefit from traditional approaches. Embryonic stem cells must be further studied to improve culturing conditions in order to achieve cellular population useful for transplantation.

The peer reviewed process

The peer review process is the current procedure to publish scientific papers. Scientists usually submit their work to the journal of choice and the editor in chief sends the manuscripts to a series of expert reviewers, able to critically judge the draft. This process should guarantee the goodness of science, but it doesn’t always correctly work.
Indeed, few months ago a group of scientists, studying stem cells, wrote an open letter tho major scientific journals, such as Science and Nature for instance. They complained the delay of data publications in their field. It seemed that some reviewers of rival institutions suggested long and useless experiments to scientists who submitted their paper, with the final aim of blocking publication and be able to publish as first. This behavior is partially explained by the financial interest related to stem cells research, because this topic is continuously funded by governmental institutions. Anyway, reviewers must be scientifically honest and this misconduct must be condemned.

In their open letter, scientists proposed to publish reviewers’ comment in the supplementary materials in order to guarantee the transparency of the process, but the main journals deny the allegations. Competition between journals is another aspect that has to be kept in account. Editors in chief are usually informed of the misconduct of reviewers – that is not limited to stem cells field, but is also present in other branches of research- but don’t want to loose the opportunity to get published the papers of reviewers self, that of course, before being reviewers, are important scientist.
An auspicable solution of this problem is more professionalism from editors and scientists, in oder to save science integrity. A second solution has been published on Plos Medicine journal: it may be possible to modify the impact factor criterion to evaluate the scientific value of a paper. Currently, the impact factor is considered when scientists choose the journal to whom submit the paper, or when job promotion has to be assigned. The impact factor is calculated on the number of citations that an article has gained: this indicates the visibility of the work in the scientific community. Dr Walker in her paper published on Plos Medicine proposed the article metrics as an alternative to impact factor criterion. The article metrics calculates how many times the article has been cited in other articles, reviews or blogs and how many times it has been viewed and downloaded. In this way, it shows the overall interest that the paper has created in the scientific community and not only the number of citations. Article metrics should make more transparent the publication process. In conclusion, for scientific advance it should be reasonable to set up the best system to conduct the publication process.

Stem cells research community

Nature journal proposes a complete and useful gateway for stem cell researcher. In this website you can find the most recent and popular papers about this topic, some suggestions for protocols and methods and an interesting blog in which exchange your opinion with other scientists in the same field of interest. Rather than scientific documentation, it’s possible to retrieve interviews of featured experts that work in biotech or pharmaceutical companies or big institutions.

Similar contacts could be useful also to generate collaboration and common projects. Moreover, the calendar of the most important events in stem cell research is also available. One tool like this is crucial to be always updated without loosing too much time in searching articles in currently used databases or meetings and conferences. Another interesting blog about stem cells is The stem cells blog, written by dr D. Granovsky. Also in this case, important information about stem cells are reported and commented. Scientific posts about stem cells and their applications in regenerative medicine are also available in this blog. Science and communication are strictly related and blogs and specific gateways can be useful tools to find out new ideas and generate new contacts and collaborations.

LIMS and stem cell research

LIMS is an acronym for Laboratory Information Management Software, is a common software used in environmental, pharmaceutical and research institutions. It’s a software to manage laboratory life, indeed with this tool it’s possible not only to manage samples and standards, users and instruments, but also to send invoices, control the automation of the workflow, manage projects. The current goal is to retain result achievement, elaboration, further decision and final review directly at the workplace, and not in the office. Indeed, all laboratory users can login and use this software, projects are organized by type, subtype, priority and other criteria and all information related are recorded within; moreover, also instruments can send data directly to LIMS that is configured to guarantee the traceability of the work. With LIMS it’s possible to save time and money and improve rate and productivity: indeed, big inventories could be reduced or eliminated at all and researchers don’t waste too much time to search data of previous experiments and so on.

Stem cell research is an exciting branch of science that quickly advances and provides data. In order to manage these data and facilitate the collaboration between institutions it could be reasonable the use of LIMS in the most upgraded version. The first feature that the software should have is to be user friendly because in one laboratory researchers could have different background and this difference could be more significant in more laboratories during a collaboration. In order to communicate results or change samples or make common decisions, a software like LIMS 247 used in all labs could help to coordinate the work. Many techniques and protocols can be applied in stem cell research, from cellular biology to molecular biology to biochemistry; the use of special software, directly configured by researchers, can help to record workflows and data and trace them: this is the second important feature of a software that should be used in stem cell research. Progress reports are also important during laboratory life, LIMS guarantees a secure mechanism for data reporting, always checked by the quality control system present in the software. We have presented one possible application of LIMS in research laboratories, but this software could be successfully employed also for the management of cell cultures and patients samples collected in hospitals. Again, to perfectly recorded every information about each sample -and when we work with patients the perfection is a must- it’s possible to use LIMS. This software can help researchers to maintain the traceability of the samples and clinicians that can base their decisions on scientific data from the same samples. This process could improve the results from regenerative medicine, in the case of stem cell research, but in all clinician departments could give a great hand. Modern science, specially stem cell research that is the future for medicine and biology, cannot exclude informational tools from its life: software like LIMS 247 from RURO Inc. could improve the quality of scientific works and increase the data and publications productivity and the quality of the clinical services for patients.

New guidelines for stem cells research

Stem cells have implications in numerous diseases or congenital defects; studying this kind of cells will allow us to understand important biological mechanism and care for instance cancer, neurological problems and so on. Several ethical issues are related to stem cells research, in particular to embryonic stem cells, and public debate has often limited the advance of science in this field.

In March 2009, US president B. Obama changes the policy about stem cells in respect of his predecessor G.W. Bush and revokes the limitations for federal funding for research involving human embryonic stem cells. The National Institute of Health (NIH) supports actions that lead to exploration of human stem cells and show great benefits for the whole humankind. Secretary reviews the existing NIH guidelines and writes new guidance for scientists involved in stem cell research. All these documents allow to simplify procedures for funding stem cells research and guarantee the governmental agreement towards new discoveries and new applications in this field. Stem cells research represents a great challenge for next generation of scientists and an hope for patients affected by serious diseases, such as cancer. It’s also important to remember that a long way has to be performed to obtain clinically relevant results.

Stem cells nomenclature

Stem cells appellation derives from German Stammzelle that defines firstly the evolutionary unicellular ancestor of multicellular organisms and secondarily the ancestral stem cell in an organism, initially in the germ line. Subsequently this term was applied to other tissues, generating some confusion.

In particular some problems arise with the notions of precursor and progenitor: indeed we talk about progenitor if the appellation of stem cells leaves doubts about the nature of the cells, while precursor is usually used to define the ancestral embryonic cell in the lineage of interest –for instance blasts are precursors of neuroblast, myoblast and so on- General and frequently accepted criteria to define one stem cell are the self renewal and the transit amplification; another criterion that has been proposed is the classification of cell states in terms of epigenetic, chromatin rearrangement and gene- expression. In this way it could be possible to distinguish stem cell from progenitor and precursor without nomenclature bias. Also the assumption that in one tissue only one stem cell is present, could be corrected and when cell stem signature will be done, it could be possible –and reasonable- to identify different stem cells with different genetic signatures.

Challenges in pluripotency

Pluripotency is a special feature of stem cells to renew and generate part of the body. Totipotency is characteristic of embryonic stem cells that can generate each organ or tissue, while pluripotency is more limited and only few tissue can be product by stem cells. Four factors seem to control pluripotency: Oct4, Klf4, Myc, Sox2.

All these genes are crucial during embryonal development and in some cases mutations could lead to serious diseases, such as cancer for Myc gene, or impaired development for Oct4 and Sox2. A recent work published on Nature journal demonstrated that, by using these four factors (previously used to reprogram fibroblast), it could be possible to generate human pluripotent stem cells from fetal, neonatal and adult primary cells. Human induced pluripotent cells showed similar features of embryonic stem cells in terms of morphology and gene expression and were able to form teratomas when injected in immuno-deficient mice. This work opens new perspectives in stem cells research: for instance in next future, it could be possible to culture primary cells directly form patients and induce pluripotent cells in order to repair tissue, make transplantation or care degenerative diseases without troubles of rejection.

Challenging on data management

Data management is a crucial aspect of scientific work, not only to correctly collect and retrieve information, but also to constantly have a complete vision of the work. In quality control system, data are classified by a code, defined by scientists and common for all laboratory members. For instance, files can be named with date, operator, project and kind of experiment: in this way it’s possible to identify one file without loosing time to check all folders and open every document.

Otherwise, it’s possible to use special software that is commercially available to manage your data. In lab research different kind of data can be generated: firstly raw data, such as numbers, pictures or texts (for example patient interview in clinical studies). Raw data have to be conserved, retrievable and in some cases protected by password, especially in clinical studies when sensible information about patient’s health are collected. These data can derive from several instruments that work with their specific program: they have to be converted in a unique format in order to be useful for elaboration. Raw data are usually resumed in graphs or tables that can immediately and communicate the result from complex experiments. At this point, it’s crucial to choose the best way to communicate results and valorize your work. Indeed, few graphs and table in scientific article have to present a long work made by several scientists in some cases. A correct data management system is useful during article writing to retrieve all important information and it’s cost- effective because avoid to loose time in searching raw or elaborated data or in repeating experiments those data are missing.

Not only in laboratory research, but also in clinical trial is important to correctly manage data for different reasons: firstly in clinical trials data often derive from patients and are subjected to privacy law, secondarily a really large amount of data are usually produced, especially during latest phases of trial when thousand patients are enrolled, lastly clinical trials are expensive and correctly managing data decreases costs. Data management software is feature-rich and includes planning, preparation and performance rather than raw data collector. Moreover, scientist contact information, deadlines, milestones and progress report have to be available to allow a complete overview of the project. The software is usually used in different centers around the world because clinical trials involve several institutions and must be user-friendly and verified from external intrusion.

In conclusion, data management is a challenging aspect of modern science for many reasons: data generated from research or clinical studies are a huge amount and often derive from different institutions that collaborate: this means that coordination between centres in data collection is essential; moreover, data are conserved and protected in respect of quality control standard and privacy law, respectively. Modern and efficient software is available now, and in next future it’s necessary to further customize IT products in order to make data management easier and less expensive.

Regeneration of eyes

Advances in regenerative medicine allow to repair important damages at eyes. Now it could be possible to culture in vitro photoreceptor precursors and stem cells from retinal pigmeted epithelium and transplant them into patient’s eyes. The goal of this therapy is to improve sight and give the opportunity to patients to recognize again faces and read. Why do eyes give so important and positive results?

Transplantation of stem cells into eyes doesn’t generate teratomas even if in some cases in mice eye tumour has been observed. Eyes are accessible to surgical intervention and the blood-retina barrier decreases the activity of immune system and immunosuppressants might be not necessary to prevent rejection. Furthermore, we have a great experience to transplant stem cells into eyes, because natural stem cells from cornea are usually cultured and transplanted to repair the damaged eye. While cornea is located at front of the eye, retina is on the back and this could represent a difficult for transplantation. Several diseases are associated to retinal damage: diabetes for instance is the most common disease that could determine loss of sight and everyone knows how diabetes is frequent in old people. In conclusion, this approach represents a great hope for all that have sight problems and scientific results seem to be really promising.

Quality control in lab

Quality control in laboratory is essential to obtain great results. Several studies demonstrated that more publications are accepted by peer reviewed journals when good laboratory procedures are followed. This means that giving the same time and the same amount of money, labs that work with GLP are more productive than those that aren’t in GLP. Good laboratory procedures are rules (SOPs) which scientists have to keep in mind when they perform experiments and have to be the same for all people working in the lab.

Standard operating procedures (SOPs) should be written for each instrumentation present in lab and represent guidelines to work with. From calibration to final cleaning, terms of use of an instrument are well described in order to guarantee firstly that instrument is correctly used, secondarily that everyone in lab uses machine in the same manner: this is a crucial point to allow comparison of results produced in lab. A training has to be done before using an instrument, at least the first time with a manufacturer’s specialist and then by the most expert person in lab. Each instrument has a responsible that takes care of management and maintenance. Ideally, in this way measurements obtained from an instrument by all users are comparable and consistent and standard deviation between repeated experiments should decrease. SOPs are not applied only to instruments use, but can also describe other important actions, normally performed in lab. For instance, when data management has well defined rules, it’s easier and faster to retrieve information. Whatever kind of data elaborated in files –texts, tables, pictures, graphs- should be classified and named with a code that, for instance, contains project number, operator, day, kind of file: so just reading the name, it should be possible to understand if we have found what we are looking for. Standardization of data management is crucial when there are a lot of people in lab or there is a quick turnover, indeed these are common cases in which some data could be lost. Writing a notebook is another part of scientific work that is essential for scientist and also this aspect has to be standardized. Indeed, in notebook protocols are usually described, raw data collected, first observations noted and each scientist tends to personalize his book.
A standardized manner of writing notebook is important to make easier sharing protocols and ideas between group members. Last but not least, all reagents from salts to enzymes, from culture media to animals, have to be registered in terms of availability, arrival date, expiration date in a common repository accessible to all people working. In this way, scientists can quickly check to have all reagents for their experiment before starting and don’t waste time and, more important, they don’t waste money to buy reagents maybe already available in lab, but hidden in some dark corner. Software is available to correctly manage all kind of scientific repository, from freezers to nitrogen tank to collect cells. In conclusion, following GLP makes experimental work more efficient and less expensive.