Human fetal tissue is critical for biomedical research.

Human fetal tissue and cells derived from fetal tissue are crucial for biomedical research. Fetal tissues and cells are used to study both normal development and developmental disorders. They are broadly applied in vaccine development and production. Further, research using cells from fetal tissue is instrumental for studying many infectious diseases, including a broad range of viruses. These widespread applications underscore the value of fetal tissue research and reflect an important point: cells derived from fetal tissues have capabilities that cells from other sources do not. In many cases, increased functionality of cells derived from fetal tissues arises from increased proliferative capacity, ability to survive in culture, and developmental potential that is attenuated in adult tissues. This review highlights important, representative applications of fetal tissue for science and medicine.

Progressive trends in prenatal genetic screening / Tendencias progresivas en el cribado genético prenatal

According to the global report on birth defects in 2021, it is estimated that 8 million children are born with birth defects of genetic origin annually. These birth defects vary in their degree of severity; where some types are mild and do not require treatment but others may necessitate lifelong medications or even cause instant death just after birth. That is why prenatal screening is doubtless necessary to detect such genetic defects before birth aiming to drop the tragedy of these children off. Recently, this approach has been developing towards non-invasive techniques that reduce the risk of miscarriage, which was common in the old-fashioned invasive ones. Non-invasive Prenatal Tests (NIPTs) like Chromosomal Microarray Analysis (CMA) and cell-free fetal DNA (cffDNA) caused a breakthrough in the screening methods of chromosomal aneuploidies. Thanks to their benefits, NIPTs are considered a fundamental clinical approach for pregnant women’ screening in multiple countries. Thence, this paper gives prominence to the recentness of NIPTs along with each’s assets, liabilities, and prospective recommendations. In addition, it would demonstrate the importance of modern molecular technologies like next-generation sequencing (NGS) which are enforced for the appliance of NIPTs. (AU)

Según el informe mundial sobre anomalías congénitas de 2021, se estima que anualmente nacen 8 millones de niños con anomalías congénitas de origen genético. Estos defectos de nacimiento varían en su grado de severidad; donde algunos tipos son leves y no requieren tratamiento, pero otros pueden necesitar medicamentos de por vida o incluso causar la muerte instantánea justo después del nacimiento. Por eso es sin duda necesario el cribado prenatal para detectar tales defectos genéticos antes del nacimiento con el fin de acabar con la tragedia de estos niños. Recientemente, este enfoque se ha ido desarrollando hacia técnicas no invasivas que reducen el riesgo de aborto espontáneo, que era común en las antiguas invasivas. Las pruebas prenatales no invasivas (NIPT) como el análisis de micromatrices cromosómicas (CMA) y el ADN fetal libre de células (cffDNA) provocaron un gran avance en los métodos de detección de aneuploidías cromosómicas. Gracias a sus beneficios, las NIPT se consideran un enfoque clínico fundamental para la detección de mujeres embarazadas en múltiples países. Por lo tanto, este documento destaca la actualidad de los NIPT junto con los activos, pasivos y recomendaciones prospectivas de cada uno. Además, demostraría la importancia de las tecnologías moleculares modernas, como la secuenciación de próxima generación (NGS), que se aplican para la aplicación de NIPT. (AU)

Fetal tissue donation for research at the time of abortion: A qualitative study of individuals who experienced an abortion in Hawaii in 2018-19.

OBJECTIVES: This qualitative study explores how individuals recently experiencing abortions feel about donating fetal tissue for research. In addition, we sought to identify motivating or discouraging factors that influence decision making for these individuals. STUDY DESIGN: We recruited individuals living in Hawaii who reported undergoing an abortion in the previous 6 months for one-on-one semi-structured interviews as part of a broader study investigating views on peri-abortion research practices and protections. We devoted approximately 15 minutes of each 1-hour interview to discussing the donation of aborted fetal tissue for research. We double coded transcribed interviews and identified themes related to fetal tissue donation. RESULTS: We interviewed 25 respondents and identified 4 themes. (1) Individuals viewed fetal tissue donation as an opportunity to help others. (2) Respondents preferred for aborted fetal tissue to be used rather than discarded. (3) Respondents viewed the fetal tissue to be an extension of themselves, so informed consent is critical. (4) Information found online promotes mistrust of fetal tissue handling. CONCLUSIONS: Individuals who have had an abortion are open to fetal tissue donation for research purposes. Pre-abortion counseling could be improved by clarifying the process of fetal tissue handling and, when available, discussing options for fetal tissue donation. IMPLICATIONS: Informed pregnant individuals who have had an abortion appear to be supportive of fetal tissue research and their views can differ from the concerns of ethicists, politicians, and scientists. The perspective of the individuals donating fetal tissue should be included in future discussions of fetal tissue research.

COVID-19 and vertical transmission: assessing the expression of ACE2/TMPRSS2 in the human fetus and placenta to assess the risk of SARS-CoV-2 infection.

BACKGROUND: Pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, but little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a prerequisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. METHODS: We performed a retrospective analysis of a single cell data repository. The data were then validated at both gene and protein level by performing RT-qPCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues. FINDINGS: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels only in the fetal intestine and kidney, and is not expressed in the fetal lung. The placenta also does not co-express the two proteins across the second trimester or at term. INTERPRETATION: This dataset indicates that the lungs are unlikely to be a viable route of SARS-CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the gastrointestinal tract is likely to be susceptible to infection due to its high co-expression of both proteins, as well as its exposure to potentially infected amniotic fluid. TWEETABLE ABSTRACT: This work provides detailed mechanistic insight into the relative protection & vulnerabilities of the fetus & placenta to SARS-CoV-2 infection by scRNAseq & protein expression analysis for ACE2 & TMPRSS2. The findings help to explain the low rate of vertical transmission.

Rescuing human fetal tissue research in the United States: A call for additional regulatory reform.

Research using human fetal tissue has saved millions of lives through vaccines and other advances, but was markedly restricted by federal regulations in 2019. Although the restrictions were partially reversed in 2021, additional regulatory changes are needed to prevent further damage to essential research programs while preserving protection for human subjects.

Pregnant Individuals' Views on Fetal Tissue Research in the United States.

OBJECTIVE: Fetal tissue research has driven significant medical advances but remains publicly contentious in the United States. The views of pregnant individuals in the United States regarding the donation of fetal tissue offer an important and previously unexplored perspective on this issue. METHODS: We conducted a secondary analysis of data from two separate, broader qualitative studies. Pregnant and recently pregnant individuals (N=79) from clinical sites at the University of North Carolina at Chapel Hill, Johns Hopkins University, and Massachusetts General Hospital were interviewed individually using a semi-structured guide addressing a range of issues related to infectious disease research and pregnancy, including the acceptability of fetal tissue research. Interviews were transcribed, coded, and analyzed for emergent themes. RESULTS: Among this sample of predominantly Black (61%), reproductive-aged pregnant and recently pregnant participants, the majority (72%) generally supported fetal tissue research. The following three themes were identified: choice, respect, and meaning. Respondents discussed the deeply personal nature of decisions surrounding fetal tissue research, emphasizing the importance of informed consent and respect for the person's emotional state when approaching for consent. The ways in which participants regarded how to respectfully handle fetal tissue also shaped views about the acceptability of donation, both for and against. For many participants, fetal tissue donation to research represented one way of ascribing meaning to pregnancy termination or loss. CONCLUSION: Among this diverse sample of pregnant and recently pregnant individuals, most were supportive of fetal tissue donation for research. A better understanding of pregnant individuals' views on this topic may lead to policies and practices that are congruent with the needs and values of people facing decisions regarding the disposition of fetal remains.

Transforming trash to treasure Cultural ambiguity in foetal cell research.

BACKGROUND: Rich in different kind of potent cells, embryos are used in modern regenerative medicine and research. Neurobiologists today are pushing the boundaries for what can be done with embryos existing in the transitory margins of medicine. Therefore, there is a growing need to develop conceptual frameworks for interpreting the transformative cultural, biological and technical processes involving these aborted, donated and marginal embryos. This article is a contribution to this development of frameworks. METHODS: This article examines different emotional, cognitive and discursive strategies used by neurobiologists in a foetal cell transplantation trial in Parkinson's disease research, using cells harvested from aborted embryos. Two interviews were analysed in the light of former observations in the processing laboratories, using the anthropologist Mary Douglas's concept of pollution behaviour and the linguist, philosopher, psychoanalyst and feminist Julia Kristeva's concept of the abjective to explain and make sense of the findings. RESULTS: The findings indicate that the labour performed by the researchers in the trial work involves transforming the foetal material practically, as well as culturally, from trash to treasure. The transformation process contains different phases, and in the interview material we observed that the foetal material or cells were considered objects, subjects or rejected as abject by the researchers handling them, depending on what phase of process or practice they referred to or had experience of. As demonstrated in the analysis, it is the human origin of the cell that makes it abjective and activates pollution discourse, when the researchers talk of their practice. CONCLUSIONS: The marginal and ambiguous status of the embryo that emerges in the accounts turns the scientists handling foetal cells into liminal characters in modern medicine. Focusing on how practical as well as emotional and cultural strategies and rationalizations of the researchers emerge in interview accounts, this study adds insights on the rationale of practically procuring, transforming and utilizing the foetal material to the already existing studies focused on the donations. We also discuss why the use and refinement of a tissue, around which there is practical consensus but cultural ambiguity, deserves further investigation.

A Letter to President Biden and Secretary Designate of HHS Xavier Becerra: Remove Barriers to Federal Funding of Human Embryo and Fetal Tissue Research.

Human fetal tissue (HFT) has been used in biomedical research for nearly a century and has led to extraordinarily valuable discoveries that have benefitted humankind. Politicization of the use of HFT over recent years has led to the creation of numerous obstacles to scientific progress in this field. In July 2019, the imposition of redundant ethics policies was supplemented with the creation of the Human Fetal Tissue Ethics Advisory Board, which withheld funding of 13 out of 14 NIH grants that were favorably peer reviewed in the Summer of 2020. We believe that these new sets of restrictions are harmful to the goals of scientific progress and call upon the new administration of our government to allow peer review, not politics, to determine scientific merit and to reinstitute the previously existing ethics policies that were more than adequate to assure the appropriateness of human fetal tissue research.

A novel method for noninvasive diagnosis of monogenic diseases from circulating fetal cells.

OBJECTIVE: To establish a method for noninvasive fetal cell isolation from maternal blood and prenatal testing of monogenic diseases by a combination of direct sequencing and targeted NGS-based SNP haplotyping from single fetal cells. METHOD: Peripheral blood of pregnant women in two families (congenital deafness and ichthyosis) was collected. After density-based separation and immunostaining with multiple biomarkers, candidate fetal cells were identified by high-throughput imagine analysis and picked up by automation. Individual fetal cells were subjected to STR-genotyping to identify their origin. Pathogenic mutations were identified by direct Sanger sequencing, and a combination of targeted NGS and SNP haplotyping using a custom panel. All the results were compared with amniotic fluid DNA. RESULTS: Fetal trophoblasts were successfully harvested from maternal blood. STR-genotyping confirmed the fetal origin. Direct sequencing of pathogenic genetic mutations in fetal cells showed consistent results with amniotic fluid samples. For congenital deafness family, NGS-based SNP haplotyping also correctly identified the fetal haplotype. This single cell haplotyping method can be used to diagnose various genetic diseases. CONCLUSION: We have established a method for noninvasive prenatal testing of monogenic diseases from circulating trophoblast cells. This cell-based NIPT can be further applied to the prenatal diagnosis of various monogenic diseases.

A Novel Tool for Non-Invasive Fetal Electrocardiography Research: the NInFEA Dataset.

In this work, a novel open-source dataset for noninvasive fetal electrocardiography research is presented. It is composed of 60 high-quality electrophysiological recordings acquired between the 21st and the 27th weeks of gestation. For each acquisition, whose average duration is 30.5 s, 24 unipolar abdominal leads and three bipolar thoracic leads were included, along with a maternal respiration signal collected by a thoracic resistive belt. The chosen electrodes positioning map allows reproducing up to ten setups presented in the scientific literature. Each biopotential recording was acquired synchronously with the corresponding fetal cardiac pulsed-wave Doppler (PWD) signal, to provide complete information about the fetal cardiac cycle, both from the electrical and mechanical point of view.This is the first dataset allowing the non-invasive fetal ECG analysis even in early pregnancies with a ground truth about the fetal heart activity, given by the PWD signal. For this reason, it can be used to assess fetal ECG extraction algorithms requiring multiple channels, eventually including maternal references. This dataset is being released on Physionet by the end of June 2020 and will be continuously improved in the framework of the Non-Invasive Fetal ECG Analysis (NInFEA) project of the University of Cagliari (Italy).

The Ban on US Government Funding Research Using Human Fetal Tissues: How Does This Fit with the NIH Mission to Advance Medical Science for the Benefit of the Citizenry?

Some have argued that human fetal tissue research is unnecessary and/or immoral. Recently, the Trump administration has taken the drastic--and we believe misguided--step to effectively ban government-funded research on fetal tissue altogether. In this article, we show that entire lines of research and their clinical outcomes would not have progressed had fetal tissue been unavailable. We argue that this research has been carried out in a manner that is ethical and legal, and that it has provided knowledge that has saved lives, particularly those of pregnant women, their unborn fetuses, and newborns. We believe that those who support a ban on the use of fetal tissue are halting medical progress and therefore endangering the health and lives of many, and for this they should accept responsibility. At the very least, we challenge them to be true to their beliefs: if they wish to short-circuit a scientific process that has led to medical advances, they should pledge to not accept for themselves the health benefits that such advances provide.