Stem Cell Niches
From the Series: Embodied Ecologies
“Inside every stem cell is an organ waiting to happen.” This statement, drawn from a recent article in Nature Methods (Eisenstein 2018, 19), suggests that stem cells lie in waiting, suspended until something comes along to bring out the potential organ within. For postgenomic stem cell science, what enables this to happen is the stem cell’s microenvironment. The bodily milieu has itself become a technology with which researchers can mimic normal and pathological organ growth in the laboratory. Paradoxically, as concerns about the Anthropocene inspire cautionary tales of human interference in the environment, manipulation of the bodily microenvironment is today viewed as the greatest promise of regenerative medicine. Stem cell researchers use notions of embodied ecologies to model development, study disease, and biomedically intervene in aging and injured bodies.
Like many other life sciences, stem cell science is in the midst of a postgenomic reorientation. As with trends in epigenetics or microbiome studies, stem cell researchers are now turning their attention to cell–microenvironment interaction (Laplane 2016). This new emphasis conceives of stem cells as relational entities, which acquire their capacities from signals received from their milieu. This shift has considerable consequences for how scientists practice their work. Those I worked with in labs in Europe and the United States not only engage biology as technology (Landecker 2007; Franklin 2013), turning biological entities into tools; they also use the particular microenvironment where stem cells reside, or what scientists call the stem cell niche, as a tool for manipulating cellular biology. The cellular niche itself becomes a technology.
This postgenomic reorientation taps into a longer history of attempting to realize the regenerative potential of stem cells. Since the field began twenty years ago, when the first human embryonic stem cell line was isolated, advocates have argued that the promise of stem cell science lies in the bioscientific understanding of phenotypic gene expression. Knowing which biological processes turn a stem cell into a stem cell, or a skin cell into a skin cell, could be applied to repairing the increasingly frail bodies of aging societies (Cooper 2006). The promise of custom-making “spare body parts” in the lab with which to cure devastating diseases has been leveraged to counter ethical contestation around embryo research, and it has motivated people to donate tissues for research (Svendsen 2011; Thompson 2013). The promise of biotechnological control has long spurred people to seek solutions for societal issues, such as an aging population, in stem cells.
The contemporary focus on the cell–niche interaction has already created new tools. Laboratory-grown organoids are minute, three-dimensional clusters of cells that resemble organs in anatomical architecture and biological function. Scientists can now grow these tiny organs for an increasing number of bodily systems, such as gut, liver, and brain, to study bodily development and disease in the laboratory. Organoids have brought tissue organization outside the body and into the culture dish, opening up previously hidden biological processes to scientific scrutiny. Some have suggested that organoids may even make research more ethical, replacing test organisms and trial populations with patient-specific in vitro test systems.
Back in 2015, a scientist I call Berta showed me how to grow gut organoids. After preparing the suspension of gut stem cells, she instructed me that the most critical step is to build their niche. The culture dish should emulate the bodily niche, what Hannah Landecker (2004, 151) describes as “building a new type of body in which to grow a cell.” Enriching the medium with growth factors and thawing the Matrigel to mimic the stiffness of gut tissue, Berta carefully assembled the gut microenvironment in a dish so that the stem cells could develop into mini-intestines. “What you're aiming for is an intact droplet of Matrigel, containing all of the [stem cells] in the middle,” she told me, her eyes fixed on the pipette with which she squirted drops of gooey Matrigel. “And then you have the medium just float around it,” she added before tiptoeing to the incubator, so that her painstakingly assembled in vitro niches would not be disturbed. The story of Berta’s niche-making illustrates how the bodily niche is at once imagined as both natural microenvironment and human intervention.
That week in 2015, Berta’s mini-intestines did not grow from the carefully assembled stem cell cultures. In fact, she had never expected this particular batch to succeed. She had deliberately exposed the cells to chemical and radiation injury in order to establish whether the cultures would still be able to give rise to organoids after exposure. By doing so, Berta had replicated not a healthy but a pathological niche found in patients with diseases associated with the intestinal tract. The organoid had allowed Berta to model a situated biological condition, thought to be representative of the conditions that specific patients in specific places experience.
Organoids, controlled through the niches that scientists make for them, can thus model what Margaret Lock has called local and situated biologies. Drawing a distinction between the two terms, Lock (2017) proposes the latter to draw attention to the fact that, in the Anthropocene, everyone is affected by human-induced environmental changes. Yet beneath this universal exposure are differentially stratified local biologies that put some populations more at risk of detrimental health outcomes than others. My research suggests a complementary approach: postgenomic stem cell science uses related notions of situatedness and localization to emulate environmental impacts from inside and outside the bodily ecosystem. This allows scientists to study which microenvironments are inductive of pathological change, and which microenvironments may be engineered to allow bodies to heal. How will knowledge generated from these cell–niche interaction studies be applied in a stratified world, where unequal burdens of toxic exposure and unequal access to healthy environments becomes more and more apparent?
Research for this post was funded by the Wenner-Gren Foundation, grant no. #8953, and the Wellcome Trust, grant no. #100606/Z/12/Z. I am grateful to Noémie Merleau-Ponty, Gabriela Hertig, and Samuel Lengen for their feedback on the text.
Cooper, Melinda. 2006. “Resuscitations: Stem Cells and the Crisis of Old Age.” Body and Society 12, no. 1: 1–23.
Eisenstein, Michael. 2018. “Organoids: The Body Builders.” Nature Methods 15: 19–22.
Franklin, Sarah. 2013. Biological Relatives: IVF, Stem Cells, and the Future of Kinship. Durham, N.C.: Duke University Press.
Landecker, Hannah. 2004. “Building ‘a new type of body in which to grow a cell’: Tissue Culture at the Rockefeller Institute, 1910–1914.” In Creating a Tradition of Biomedical Research: Contributions to the History of the Rockefeller University, edited by Darwin H. Stapleton, 151–74. New York: Rockefeller University Press.
_____. 2007. Culturing Life: How Cells became Technologies. Cambridge, Mass.: Harvard University Press.
Laplane, Lucie. 2016. Cancer Stem Cells: Philosophy and Therapies. Cambridge, Mass.: Harvard University Press.
Lock, Margaret. 2017. “Recovering the Body.” Annual Review of Anthropology 46: 1–14.
Svendsen, Mette N. 2011. “Articulating Potentiality: Notes on the Delineation of the Blank Figure in Human Embryonic Stem Cell Research.” Cultural Anthropology 26, no. 3: 414–37.
Thompson, Charis. 2013. Good Science: The Ethical Choreography of Stem Cell Research. Cambridge, Mass.: MIT Press.