Human material stored in the University hospital boosts scientific research
The need to have a collection of easily manipulated, storable human biological material becomes essential for a hospital to boost scientific research. This material today has a certain destination: it is "archived" for an indefinite period of time in biobanks, inside refrigerators at very low temperatures, which guarantees the conservation of findings of interest for present and future research. Brazil currently has around 60 biobanks in total.
The Women’s Hospital “Prof. Dr. JA Pinotti” - Caism at Unicamp has one of the first biobanks for storing placentas in the country, which joins an organized collection of human biological material donated voluntarily by patients. This collection contains the solid component of blood, serum, plasma, frozen tissue, tissue fixed in paraffin blocks, macromolecules (DNA, RNA) and proteins, as well as urine, amniotic fluid, feces and hair.
Last year, using the biobank structure already installed for the Oncology area – under the coordination of professor Luis Otávio Sarian (executive director of Caism) – obstetrician Maria Laura Costa created this placenta biobank at the height of the Zika Virus epidemic in country. There is stored material from pregnancies complicated by arboviruses or Zika, from women who gave birth in Caism.
Of the 80 placentas collected, 14 were from women with confirmed or suspected Zika Virus. “We have already started evaluating this material and studies are underway using cases with placental positivity. Assessing these cases can generate relevant results because, to this day, no one knows exactly how the virus progresses in the placenta, is transmitted to the baby and its repercussions, depending on the placental infection”, says Laura.
According to her, having material from these women, systematically collected from the different layers of the placenta and rigorously stored and processed, is essential to advance the study of the cells involved in understanding the infection process.
“We must collaborate to understand Zika infection and placental involvement”, describes the obstetrician. “The placenta [which weighs up to 500 grams] is one of the least understood human organs, as it forms the interface between mother and fetus, preventing rejection, discarding fetal waste, transferring nutrients and secreting hormones that maintain pregnancy.”
The obstetrician and collaborators have just published an article in the prestigious magazine The Journal of Infectious Diseases, from Oxford Academic, where the tone is the characterization of the inflammatory profile in cases of major complications caused by the Zika Virus in individuals with acute infection, including pregnant women.
Pre eclampsia
Another area that Laura has focused on is maternal mortality and complications in pregnancy, childbirth and postpartum. In recent years, she has been refining placental biology, trying to bring the two themes together. “We call this translational research, as it seeks to speed up the transfer of results and knowledge from basic research to research and clinical practices,” she explains.
The 80 placentas in the hospital's biobank are the result of a systematic collection that includes obtaining material from various portions of the placenta: basement membrane glued to the uterus, the umbilical cord, the amniotic membrane and the chorionic plate.
The material has been collected and stored directly in liquid nitrogen at an extremely low temperature, in order to preserve the characteristics of the tissue in future work, and material has also been stored in paraffin blocks to study the structure and morphology of the tissue.
The aim is to form a library of this material, although the use of the biobank also depends on the evolution of technology and the imagination of researchers, for the preparation and ethical approval of future research projects, highlights Laura. This material is now available for genetic and protein studies, immunohistochemistry, genetic polymorphism, gene expression and expression of different proteins.
The search is to have representative material of rare and non-rare diseases, so that, given the probability of research clarifying a certain diagnosis, prognosis and treatment, it is possible to select the best samples. A significant number of samples helps to detect weaknesses common to more than one material evaluated.
Laura's expectation is to gradually achieve a systematic and universal collection of placentas, but not just placentas. Also from other biological materials during pregnancy, collecting blood and urine from women during prenatal care, childbirth and postpartum, to correlate these findings with pregnancy complications.
At Caism, some studies are already underway in this direction, coordinated by the professor at the Faculty of Medical Sciences (FCM) at Unicamp José Guilherme Cecatti, with a sample of women who begin prenatal care without complications, from whom blood and even hair are collected to store in biobank.
In studies of maternal morbidity, the obstetrician comments that she is also interested in pregnancies with pre-eclampsia (when blood pressure is high), one of the most significant complications in pregnancy and one of the biggest causes of maternal morbidity and mortality in Brazil and in countries around the world. low and middle income. In addition to hypertension, pre-eclampsia is characterized by proteinuria – excessive loss of protein in the urine – in women after 20 weeks of gestation.
During her postdoctoral studies at Washington University, in St. Louis, USA, Laura studied women with severe pre-eclampsia to try to understand what triggers it and what immunological mechanisms cause it. She hopes to collaborate on the topic and intensify the international partnership and with colleagues from the Department of Tocogynecology at FCM.
The biobank will lead to many discoveries, the obstetrician believes. “When you have biological material stored, when a complication appears that you cannot explain, such as the Zika Virus or even pre-eclampsia, you can re-study that material from women during pregnancy and childbirth. It is also possible to obtain material from a pool of women who were pregnant in a given month, if a new epidemic occurs, for example, and thus investigate other hypotheses”, he emphasizes.
Collection
Caism pathologist Geisi Russano explains that the Women's Hospital biobank is a very complete collection. In terms of tissues, to date there have been something close to 500 samples collected, including blood and tissue, frozen at -80º C. “When I talk about frozen tissue, I am referring to the placenta and breast tissue. Soon, we will also have ovaries,” she reveals.
Everything is very organized, according to the pathologist. All biological materials are stored in barcoded tubes. Another thing: when there are temperature fluctuations in the freezers that store them, at least three doctors are contacted by email in order to resolve the problem.
The Caism biobank was approved by the National Research Ethics Commission (Conep) and all works that intend to use its samples are approved by the Caism Research Committee and the FCM Research Ethics Committee (CEP).
Patients who agree to donate material to this biobank sign a consent form, which explains what the biobank is, how the material is stored and the research that can be carried out with it. The biobank is always linked to research, points out Geisi, however the priority is diagnosis, especially in cases of Oncology.
Before biobanks were formed in the USA, in the 1990s, research was more laborious, always carried out in biorepositories and mostly in paraffin blocks. “Today, with frozen tissue, a good quantity and quality of DNA and RNA samples can be obtained”, he guarantees.
Laura recalls that, if a researcher wanted to analyze a placenta from a Zika patient in the past, they had to write a project, prove that it was essential, follow these women, collect their material and be responsible for storing and processing the samples. “Today, if the intention is to study Zika, it is now possible to have access to all cases collected and stored in the biobank, as long as they follow ethical criteria and are approved.”
Caism has excellent quality material, Geisi guarantees, and can be stored indefinitely, for decades or centuries. “We have two refrigerators at -80º C, one at -150º C and a refrigerator at -20º C, where the macromolecules are stored. With all this care and cutting-edge research, the best results are certainly yet to come,” he reflects.