IMR-90 cells are a line of normal human lung fibroblasts, originally derived from fetal tissue in 1977, that have become one of the most widely used cell lines in aging, cancer, and genomics research. Their appeal lies in their normality: unlike the immortalized tumor-derived lines that dominate many laboratory shelves, IMR-90 cells carry a standard human chromosome set (46,XX) and age predictably in culture, eventually stopping division in a process called replicative senescence. That combination of genetic normalcy and built-in aging makes them an unusually versatile tool for studying how human cells grow old, respond to damage, and resist cancer.
Where IMR-90 Cells Come From
The line was established at the Institute for Medical Research in Camden, New Jersey, which gives the cells their name. They were isolated from the lung tissue of a clinically normal 16-week-gestation female fetus. Because fetal tissue yields cells with a long but finite replication capacity, the resulting culture could be expanded, frozen at early passages, and distributed to labs worldwide while remaining genetically stable for a useful number of doublings. IMR-90 cells are commercially available from repositories like the American Type Culture Collection (ATCC) and the Coriell Institute, and they have appeared in thousands of published studies across dozens of fields.
A 2025 genome project produced chromosome-level, phased assemblies covering about 6.0 billion base pairs for IMR-90, confirming the 46,XX karyotype and identifying more than 50,000 structural variants when compared to the most complete human reference genome. Most of those variants were unique to the cell line and present on only one copy of each chromosome, underscoring that even “normal” cells carry a substantial load of private genomic variation.1Nucleic Acids Research. Haplotype-resolved genome assemblies of BJ and IMR-90 human fibroblast cell lines reveal extensive structural variation and enable reanalysis of historical sequencing data
The Consent Question Behind the Line
IMR-90 cells were established in an era before formal research-use consent for clinical biospecimens was standard practice. That means the original tissue donor and her family almost certainly did not provide explicit consent for the cells to be used the way they have been. When the genome assembly team wanted to publicly release the full IMR-90 sequence, an institutional review board had to weigh whether sharing the data could identify the donor or her relatives, and whether that posed risks to them or to their community.2Nucleic Acids Research. Haplotype-resolved genome assemblies of BJ and IMR-90 human fibroblast cell lines reveal extensive structural variation and enable reanalysis of historical sequencing data – Section: Ethics statement The review ultimately allowed data sharing, but the situation echoes broader debates about legacy cell lines and informed consent that researchers working with any historically derived human material have to grapple with.
A Workhorse for Senescence Research
If there is one area where IMR-90 cells have left the deepest mark, it is the study of cellular senescence, the state in which a cell permanently stops dividing but remains alive, metabolically active, and capable of influencing its neighbors. Senescence matters because it is both a barrier against cancer (cells that cannot divide cannot form tumors) and a contributor to aging (accumulated senescent cells drive chronic inflammation in tissues). IMR-90 cells enter senescence reliably, making them a go-to model for dissecting the process from multiple angles.
Researchers trigger senescence in IMR-90 cells in several ways. The most straightforward is simply letting them divide until they exhaust their replicative capacity. But labs often want senescence on a faster, more controlled schedule. One popular method is oncogene-induced senescence, where cells are engineered to switch on a cancer-promoting gene like RAS or Raf. In the late 1990s, researchers showed that activating a form of the Raf kinase in IMR-90 cells halted division within two days and triggered hallmarks of senescence, including the well-known senescence-associated beta-galactosidase staining, within five to six days.3Genes & Development. Senescence of human fibroblasts induced by oncogenic Raf A refined version of the approach uses an inducible RAS system in IMR-90 cells treated with tamoxifen, producing a coordinated wave of senescence that recapitulates growth arrest and the senescence-associated secretory phenotype, the cocktail of signaling molecules that senescent cells pump into their surroundings.4PubMed. IMR90 ER:RAS: A Cell Model of Oncogene-Induced Senescence
Other triggers include irradiation and drug treatment. A proteomic study used X-irradiation, inducible RAS, and the HIV protease inhibitor atazanavir to drive senescence in IMR-90 cells and then cataloged the secreted proteins, identifying hundreds of factors that senescent cells release, many of which had not been linked to senescence before.5PLOS Biology. A proteomic atlas of senescence-associated secretomes for aging biomarker development Work like this has turned IMR-90 cells into a reference platform for understanding how senescent cells communicate with surrounding tissue, a question with direct relevance to age-related diseases and to the emerging field of senolytic drugs designed to clear senescent cells.
Telomere Shortening in Real Time
Each time a cell divides, the protective caps at the ends of its chromosomes, called telomeres, get a little shorter. When they become critically short, the cell treats the unprotected chromosome ends as damage and enters senescence. IMR-90 cells lack a mechanism to rebuild their telomeres, so they are a clean system for watching this erosion happen. A 2024 study using long-read sequencing measured telomere lengths across population doublings in an IMR-90 derivative and found that the average bulk telomere length fell from about 4,276 base pairs at an early passage to roughly 2,746 base pairs at a late passage, a loss of around 39 base pairs per doubling.6Nature Communications. High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer That steady, measurable decline makes the cells useful for calibrating telomere-measurement technologies and for testing whether interventions can slow or accelerate the shortening rate.
Epigenomic Landscapes and Chromatin Remodeling
Beyond the DNA sequence itself, cells regulate which genes are accessible through chemical modifications to histones (the proteins around which DNA is wrapped) and to the DNA itself. IMR-90 cells have been central to mapping these patterns. A landmark comparison of chromatin modifications in embryonic stem cells and IMR-90 fibroblasts found that nearly a third of the genome differs in chromatin structure between the two, with large blocks of repressive histone marks expanding dramatically in the fibroblasts.7PubMed Central. Distinct epigenomic landscapes of pluripotent and lineage-committed human cells Those findings helped establish just how extensively chromatin is remodeled as cells commit to a specific identity.
The epigenomic story continues during senescence. When oncogene-induced senescence is triggered in IMR-90 cells, chromatin reorganizes into dense structures called senescence-associated heterochromatin foci. A recent study found that growing IMR-90 cells under low-oxygen conditions increased histone methylation, which protected histones from being clipped by an enzyme and prevented those heterochromatin foci from forming normally. That finding links oxygen levels, an often-overlooked variable in cell culture, to the epigenetic changes that define the senescent state.8Nucleic Acids Research. Hypoxia increases methylated histones to prevent histone clipping and heterochromatin redistribution during Raf-induced senescence
Reprogramming IMR-90 Cells to Pluripotency
One of the more dramatic things you can do with a differentiated cell is erase its identity and turn it back into something resembling an embryonic stem cell, a process called reprogramming. IMR-90 cells were among the first human somatic cells successfully reprogrammed to induced pluripotent stem cells (iPSCs), and they remain a standard starting material for testing new reprogramming methods. Researchers have coaxed IMR-90 cells into iPSCs using adenoviral delivery of reprogramming factors, producing colonies that stained positive for pluripotency markers within just a few days of transduction.9Biology Open. Co-expression networks in generation of induced pluripotent stem cells
Other groups have shown that the same reprogramming works with non-viral, mRNA-based methods, with IMR-90-derived colonies sustaining over 37 passages on feeder cells and passing various pluripotency tests.10Stem Cell Research. Generation of human induced pluripotent stem cells using non-synthetic mRNA Low oxygen conditions also boost reprogramming efficiency in IMR-90 cells, with cultures kept at two or five percent oxygen producing more iPSC colonies than those at normal atmospheric oxygen.11Cell Stem Cell. Stage-Specific Role of Hypoxia-Inducible Factors during Human Pluripotent Stem Cell Reprogramming The consistent performance of IMR-90 cells across these varied protocols makes them a benchmark when evaluating whether a new reprogramming strategy actually works.
DNA Damage Repair
Because IMR-90 cells are normal (non-transformed) human cells with intact DNA repair machinery, they serve as a baseline for understanding how healthy cells handle genomic insults. After exposure to gamma radiation, IMR-90 cells develop the expected foci of DNA damage markers. In experiments where a specific repair protein called p54(nrb) was knocked down, the cells could still detect damage normally but took significantly longer to clear it, with delayed repair visible at two and four hours post-irradiation before catching up by eight hours.12Nucleic Acids Research. Involvement of p54(nrb), a PSF partner protein, in DNA double-strand break repair and radioresistance
The cells have also been used to study what happens when DNA replication goes wrong. Overexpressing a replication-licensing factor in IMR-90 cells triggered checkpoint activation and double-strand breaks, but without the runaway re-replication seen in some tumor cell lines. This more restrained response confirmed that normal cells have stronger safeguards against replication errors, and further experiments showed that homologous recombination is the critical repair pathway keeping these cells alive under replication stress.13Journal of Biological Chemistry. Homologous Recombination and Microhomology-mediated End Joining Repair DNA Double-strand Breaks Induced by DNA Rereplication
Mitochondrial Dysfunction and Oxidative Stress
Senescent cells do not just stop dividing. Their mitochondria often malfunction, leaking reactive oxygen species and losing membrane integrity. IMR-90 cells have been instrumental in connecting this mitochondrial decline to the broader senescence program. One line of research showed that when RRM2B, a protein upregulated by the tumor suppressor p53 during senescence, was knocked down in IMR-90 cells, reactive oxygen species levels climbed and mitochondrial membranes lost their electrical charge, suggesting that RRM2B normally helps buffer the oxidative stress that comes with senescence.14Scientific Reports. RRM2B Suppresses Activation of the Oxidative Stress Pathway and is Up-regulated by P53 During Senescence
Environmental toxicants can also push IMR-90 cells into premature senescence via mitochondrial damage. Acrolein, a reactive compound found in cigarette smoke, induced senescence markers in IMR-90 cells alongside drops in mitochondrial membrane potential and reduced activity of several respiratory chain complexes.15PubMed. A cigarette component acrolein induces accelerated senescence in human diploid fibroblast IMR-90 cells Similarly, lipid peroxidation products, reactive molecules generated when fats break down under oxidative stress, triggered the senescence program in IMR-90 cells while simultaneously damaging mitochondrial proteins and cutting spare respiratory capacity.16PubMed Central. Lipid peroxidation products induce carbonyl stress, mitochondrial dysfunction, and cellular senescence in human and murine cells Collectively, these studies paint mitochondria as both victims and amplifiers of the damage cascade that drives cells into senescence.
Virology and Innate Immunity
Before senescence research eclipsed everything else, one of the original practical uses of human diploid fibroblast lines was growing viruses for diagnostic and vaccine purposes. IMR-90 cells support the growth of many common respiratory and other viruses, and their viral recovery rates are comparable to those of the older WI-38 and MRC-5 lines.17PubMed Central. Comparison of WI-38, MRC-5, and IMR-90 cell strains for isolation of viruses from clinical specimens
More recently, IMR-90 cells have been used to study how normal human cells detect and fight viral infection. Because they are not transformed, their innate immune signaling is intact and representative of healthy tissue. Experiments knocking down the protein PACT in IMR-90 cells showed that this protein is needed for full activation of the interferon-beta response to Sendai virus infection; without PACT, infected IMR-90 cells produced less interferon, and the culture medium they generated was less protective when transferred to fresh cells.18Cell Host & Microbe. The Double-Stranded RNA-Binding Protein PACT Functions as a Cellular Activator of RIG-I to Facilitate Innate Antiviral Response Adenovirus researchers have also used arrested IMR-90 cells to study how viral early proteins reprogram the host cell’s gene expression, using RNA sequencing to map the transcriptional changes driven by different adenovirus mutants.19PLoS One. Cellular transcriptomics of arrested normal lung fibroblasts IMR-90 infected with Human Adenovirus 5 E1A mutants
Toxicology Testing and Drug Screening
The fact that IMR-90 cells are non-tumoral lung fibroblasts gives them a specific role in toxicology: they can serve as the “normal cell” control when researchers want to know whether a compound is selectively toxic to cancer cells or harmful to healthy tissue as well. A study of carnosic acid, a plant-derived compound, tested its effects on both a lung cancer cell line and IMR-90 cells, examining differences in cell cycle arrest, apoptosis, and molecular signaling between the two.20PubMed. Carnosic acid exhibits antiproliferative and proapoptotic effects in tumoral NCI-H460 and nontumoral IMR-90 lung cells The cells play a similar role in nanomaterial safety research, where they have been used to evaluate how plastic nanoparticles are taken up and whether they cause DNA damage or cytotoxicity in normal lung tissue.21PubMed. Comparison of Genotoxicity and Cytotoxicity of Polyvinyl Chloride and Poly(methyl methacrylate) Nanoparticles on Normal Human Lung Cell Lines
How Matrix Stiffness Changes Everything
Cells do not grow in a vacuum; they sit on and interact with an extracellular scaffold whose physical properties feed back into cell behavior. IMR-90 cells have been particularly useful for showing that the stiffness of that scaffold matters enormously. Lung fibroblasts grown on soft substrates mimicking healthy lung tissue exert very little force on their surroundings, while the same cells on stiff substrates mimicking fibrotic lung tissue ramp up their contractile forces dramatically. The growth factor TGF-beta, a major driver of fibrosis, amplifies this effect on stiff surfaces but has almost no impact on soft ones, even though the initial signaling response inside the cell is the same either way.22PubMed Central. Improved throughput traction microscopy reveals pivotal role for matrix stiffness in fibroblast contractility and TGF-β responsiveness
The regulatory proteins YAP and TAZ help explain the connection. On stiff matrices, both proteins accumulate in the nuclei of fibroblasts, switching on programs for matrix production and cell contraction. On compliant matrices resembling normal lung, they stay out of the nucleus and those fibrotic programs remain off. Knocking down both YAP and TAZ reduced matrix synthesis, contraction, and proliferation selectively on stiff surfaces, with no effect on compliant ones.23PubMed Central. Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis And the stiffness variable extends to senescence itself: when IMR-90 cells were made senescent by the chemotherapy drug doxorubicin on substrates of different stiffness, the secretory profiles and gene expression patterns were distinct depending on the substrate, with stiff surfaces favoring collagen-enriched signatures.24PubMed Central. Substrate stiffness dictates unique doxorubicin-induced senescence-associated secretory phenotypes and transcriptomic signatures in human pulmonary fibroblasts These findings have practical implications for anyone growing IMR-90 cells: the plastic dishes used in most labs are far stiffer than any tissue in the body, meaning that standard culture conditions may push the cells into a partially activated fibrotic state that does not reflect their behavior in a living lung.
How IMR-90 Cells Compare to WI-38 and MRC-5
IMR-90 cells are not the only normal human lung fibroblast line available. WI-38 (established in 1962) and MRC-5 (established in 1966) are older alternatives, and labs sometimes treat the three as interchangeable. For many purposes they are: all three are diploid, all senesce, and all support similar virus growth. But there are differences worth knowing about. A direct comparison found that IMR-90 cells entered crisis by around generation 20, while MRC-5 and WI-38 cells stayed healthy until generation 36, giving those older lines a longer usable lifespan in culture.25PubMed Central. Comparison of WI-38, MRC-5, and IMR-90 cell strains for isolation of viruses from clinical specimens That shorter window is a practical nuisance for labs doing routine viral diagnostics but is less of an issue for senescence researchers who specifically want cells approaching their replicative limit.
In terms of biochemical responses, the three lines overlap substantially. Proteasome inhibition, for instance, produced a senescence-like phenotype in IMR-90, MRC-5, and WI-38 cells alike.26PubMed. Proteasome inhibition induces a senescence-like phenotype in primary human fibroblasts cultures Still, because the three lines come from different donors with different genetic backgrounds, they are not truly interchangeable at the genomic level, and findings from one should ideally be confirmed in at least one of the others.
Single-Cell Heterogeneity Within Senescent Populations
One of the surprises that has emerged from modern genomics is that senescence is not a single uniform state. When researchers performed single-cell RNA sequencing on IMR-90 cells over a 12-day senescence time course, they found substantial heterogeneity in gene expression both within individual time points and across the full trajectory.27bioRxiv. A Single Cell Time Course of Senescence Uncovers Discrete Cell Trajectories and Transcriptional Heterogeneity In other words, a flask of “senescent IMR-90 cells” is not a uniform population. Different cells take different molecular routes to reach growth arrest, and they end up expressing different sets of genes once they get there. That heterogeneity matters for anyone trying to target senescent cells therapeutically, because a drug that kills one subtype might leave another untouched.
This kind of single-cell resolution would have been impossible when IMR-90 cells were first established in the 1970s. The fact that the same cell line is still generating genuinely new biological insights nearly half a century later speaks to its enduring value as a model system, and to how much of cell biology depends not just on having the right cells, but on having the right technology to interrogate them.