Library · Biology & lab methods
What Cell Culture & Co-Culture Engineering got wrong, from 63 theses
Summary written by a model from the records below: Cell culture and co-culture engineering efforts frequently encounter performance trade-offs, spatial competition, and physiological mismatches across diverse culture formats. Across microbial, mammalian, and tissue models, researchers struggle with interspecies competition, media incompatibilities, transport limitations, and poor translation to in vivo conditions. These records come from graduate theses, 2021 to 2025, each labeled with its degree where the repository states it, and each links to its thesis. They were extracted by language models reading the full text, so treat each as a lead to read, not a verdict.
Plus 10 problems the authors left open, listed at the end.
Failure modes, by theses reporting them
Select a mode to jump to its records.
Synthetic microbial consortia underperform single strain monocultures
Multi-strain co-cultures and division of labor consortia achieved lower growth rates, final biomass, and degradation performance than isolated monocultures. Resource competition and negative interspecies interactions prevented engineered communities from exceeding single-strain metabolic and functional capacities.
Tried and failed
bacterial coculture for biodegradation applied to single-compound xylene degradation. Outcome: worse than baseline. Reason: coculture exhibited lower removal efficiency than single-strain monoculture
Study of a Bacterial Coculture for Benzene, Toluene, Ethylbenzene and Xylene Degradation · York University · Master's
Tried and failed
division of labour in microbial consortia applied to stress tolerance in engineered yeast. Outcome: worse than baseline. Reason: consortia exhibited lower growth and reduced stress tolerance compared to co-expressing monocultures under oxidative stress
Engineering division of labour in Yarrowia lipolytica to relieve the metabolic burden of polysaccharide degradation · Imperial · PhD
Tried and failed
synthetic microbial consortium division of labour applied to heterologous polysaccharide degradation in yeast. Outcome: worse than baseline. Reason: two-strain consortium showed significantly lower growth than single-strain co-expression monocultures
Engineering division of labour in Yarrowia lipolytica to relieve the metabolic burden of polysaccharide degradation · Imperial · PhD
Tried and failed
increasing heterologous gene copy number applied to division of labour microbial consortia. Outcome: worse than baseline. Reason: increasing copy numbers did not increase the growth advantage of the consortium over the co-expressing monoculture
Engineering division of labour in Yarrowia lipolytica to relieve the metabolic burden of polysaccharide degradation · Imperial · PhD
Tried and failed
bacterial coculture for biodegradation enzyme induction applied to aromatic hydrocarbon degradation. Outcome: worse than baseline. Reason: coculture exhibited several-fold lower catabolic enzyme activity compared to single-strain baselines
Study of a Bacterial Coculture for Benzene, Toluene, Ethylbenzene and Xylene Degradation · York University · Master's
Lost to a baseline
F1 & WT co-culture had a lower AUC (5162.25) than the halved F1 mono-culture benchmark (5807.11) at 10 mM succinate.
Investigating the role of chemotaxis in the natural source zone depletion of petroleum hydrocarbons · Imperial · PhD
Lost to a baseline
Single ethylbenzene degradation achieved 85% removal by coculture, slightly beaten by S. fonticola (97%) and M. esteraromaticum (92%) monocultures.
Study of a Bacterial Coculture for Benzene, Toluene, Ethylbenzene and Xylene Degradation · York University · Master's
Lost to a baseline
Single xylene degradation by coculture removed 14 mg/L (62%), losing to M. esteraromaticum monoculture alone which achieved 22.5 mg/L removal (87-88%).
Study of a Bacterial Coculture for Benzene, Toluene, Ethylbenzene and Xylene Degradation · York University · Master's
Lost to a baseline
Autotrophic and mixotrophic microalgal consortia reached a final biomass density almost two-thirds lower than the Chlorella vulgaris monoculture (density <0.4 g/L vs >0.4 g/L, p<0.05).
Contaminants of Emerging Concern Treatment by Microalgae: The Status and Future of Phycoremediation · Queen's University · Master's
Lost to a baseline
Single-amylase strain Y8TO1 outperformed both the double-amylase monoculture Y8TT18TO1 and the consortium Y8TT1+Y8TO1 in OD600 at 18 and 24 hours in flasks.
Engineering division of labour in Yarrowia lipolytica to relieve the metabolic burden of polysaccharide degradation · Imperial · PhD
Lost to a baseline
F1 & cheA co-culture had lower area under curve (AUC 8594.99) than the F1 mono-culture baseline (AUC 11614.22) at 10 mM succinate due to cell collisions or competition.
Investigating the role of chemotaxis in the natural source zone depletion of petroleum hydrocarbons · Imperial · PhD
Lost to a baseline
In 2% starch (no xylan), the monoculture Y8TO1TA1XC achieved higher OD600 (24.49) than all three DOL consortia (generalist 14.27, orthogonal 15.10, cross-feeding 16.33).
Engineering division of labour in Yarrowia lipolytica to relieve the metabolic burden of polysaccharide degradation · Imperial · PhD
Lost to a baseline
Double-amylase monoculture YTG18TO1 outperformed the YTG1+Y8TO1 consortium in growth rate (0.226 hr-1 vs 0.095 hr-1) and carrying capacity (45.467 vs 21.434 OD600).
Engineering division of labour in Yarrowia lipolytica to relieve the metabolic burden of polysaccharide degradation · Imperial · PhD
Lost to a baseline
Single-amylase strain YTO1 outperformed both the double-amylase monoculture YTT3TO1 and the consortium YTT3+YTO1 in OD600 at 24 hours.
Engineering division of labour in Yarrowia lipolytica to relieve the metabolic burden of polysaccharide degradation · Imperial · PhD
Three dimensional scaffolds and organoids suffer from transport limitations and handling complexity
Hydrogel encapsulation and 3D organoid platforms frequently caused lower cellular metabolism, reduced differentiation efficiency, and restricted nutrient diffusion compared to simpler cultures. These 3D architectures also introduced difficulties with cell retrieval, imaging quantification, and spatial growth control.
Lost to a baseline
3D differentiation in all STH formulations resulted in significantly lower O4+ oligodendrocytes (STH-2: 13.63%, STH-3: 17.30%) compared to 2D laminin culture baseline (23.24%).
Towards Improved Myelination: Engineering Bioinstructive Scaffolds for Schwann Cell Differentiation and Shear-Thinning Hydrogels for Oligodendrocyte Progenitor Therapy · University at Buffalo · PhD
Lost to a baseline
2D cultures displayed significantly higher resazurin turnover and higher initial AP activity (~1.6 pmol/min vs 0.2–0.4 pmol/min) compared to 3D cryogel cultures
Osteogene Differenzierung von mesenchymalen Stammzellen des Fettgewebes auf vier verschiedenen 3D-Trägermaterialien im Vergleich zu einer 2D-Kultur · Tübingen · PhD
Lost to a baseline
2D monolayer culture produced substantially higher urea (up to 3.120 µg/10^6 cells/h) compared to 3D bioreactor culture (max 0.502 µg/10^6 cells/h).
Wiederbesiedlung einer azellularisierten Lebermatrix mit primären porcinen Hepatozyten sowie Kultivierung in einem Bioreaktor · Tübingen · PhD
Lost to a baseline
2D monolayer demonstrated active galactose consumption (up to 1.72 mg/10^6 cells in first 24 h) whereas bioreactor 3D cultures showed zero elimination.
Wiederbesiedlung einer azellularisierten Lebermatrix mit primären porcinen Hepatozyten sowie Kultivierung in einem Bioreaktor · Tübingen · PhD
Considered and rejected
Considered and rejected: 3D ECM scaffold construct culture for primary AML assays was rejected/bypassed in favour of a 2D thin-film ECM scaffold due to low cellular recovery and retrieval issues from dense 3D pores.
Modelling Bone Marrow Extracellular Matrix Interactions Reveal CD36-Dependant Vulnerabilities in Acute Myeloid Leukemia · York University · Master's
Considered and rejected
Considered and rejected: Rejected 3D cell culture in favor of 2.5D culture due to imaging complexity, difficult nucleic acid/protein retrieval, and non-reproducibility issues.
Combining extracellular matrix hydrogels and electrical stimulation to influence macrophage polarisation · Nottingham · PhD
Considered and rejected
Considered and rejected: Rejected 3D organoid/microsphere culture protocols in favor of 2D monolayer cultures to enable high-throughput screening and automated immunocytochemical quantification, despite lower otic cell yields.
Erzeugung von otischen Vorläuferzellen aus humanen induzierten pluripotenten Stammzellen · Tübingen · PhD
Considered and rejected
Considered and rejected: 3D spheroid co-culture was abandoned in favor of 2D culture because spheroid formation and macrophage integration varied dramatically across lung cancer cell lines and was too labor intensive.
Exploiting Multi-Cell Type Cultures to Elucidate Tumor Cell Features That Impact Macrophage Phenotype · UT Southwestern · PhD
Considered and rejected
Considered and rejected: 3D brain assembloids deferred in favor of 2D mixed neural cultures for scalability and cost-effectiveness in proof-of-concept testing.
ApoE isoforms modulate SARS-CoV-2 neurological infection and confer differential risks for infection-driven early AD pathogenesis through vascular injury · Johns Hopkins · Master's
Tried and failed
layered hydrogel sandwich culture applied to in vitro organoid growth regulation. Outcome: unstable. Reason: stem cell zones lacked intrinsic feedback control, resulting in uncontrolled exponential fission unlike in vivo
Tissue intrinsic properties of regeneration in homeostasis and injury in the mammalian small intestine · Harvard · PhD
Tried and failed
high-density cell encapsulation in hydrogel scaffolds applied to 3D tissue culture scaffold. Reason: Spatial constraints and cell crowding prevented cellular proliferation and growth within the matrix.
Development of a three-dimensional in vitro vascularized human skin equivalent employing collagen/keratin hydrogels · UT Austin · PhD
Tried and failed
decellularised tissue extracellular matrix hydrogels applied to organoid cell culture. Outcome: worse than baseline. Reason: demonstrated inferior performance for organoid culture compared to standard reconstituted basement membrane matrix
Extracellular matrix hydrogels for endometrial regeneration · Imperial · PhD
In vitro culture environments fail to replicate in vivo physiology and dynamics
Static and isolated culture models failed to replicate the dynamic mechanical forces, tissue architecture, and multi-lineage signaling found in living organisms. As a result, in vitro systems generated artifacts, misestimated drug and metabolic dynamics, and failed to predict organismal phenotypes.
Tried and failed
monoculture susceptibility assays in nutrient-rich media applied to predicting multispecies community composition under stress. Outcome: did not generalise. Reason: In vitro single-species susceptibility tests fail to capture interspecies interactions and complex ecological dynamics in polymicrobial communities
IDENTIFYING MICROBIAL BIOMARKERS OF CYSTIC FIBROSIS HEALTH AND DISEASE · Georgia Tech · PhD
Tried and failed
static 3D hydrogel cell culture applied to modeling in vivo cellular secretomes. Outcome: did not generalise. Reason: Without dynamic fluid perfusion, static 3D cultures phenotypically clustered with 2D static cultures rather than in vivo models
High-throughput 3D on-chip potency assay for cell therapy products · Georgia Tech · PhD
Tried and failed
in vitro high-throughput droplet co-culture assays applied to predicting in vivo microbial coexistence outcomes. Outcome: did not generalise. Reason: In vitro media failed to recapitulate host environment dynamics allowing coexistence in vivo but not in vitro
Bacterial Interspecies Interactions and Microbial Community Assembly · MIT · PhD
Tried and failed
ex vivo tissue co-culture induction applied to helminth egg hatching. Outcome: no signal. Reason: Human colon biopsies and stool failed to trigger egg hatching in vitro
Characterisation of Host- Parasite- Microbiota Interactions that Drive Hatching in Trichuris Species · Cambridge · PhD
Tried and failed
in vitro culturing to replicate volatile emission differences applied to host-associated microbial isolates. Outcome: no signal. Reason: isolated culture plates did not reproduce differential volatile profiles observed in vivo
WHEN FLOWERS PLAY DEAD: MICROBES AS ARCHITECTS OF A ‘DECEPTIVE’ FLORAL PHENOTYPE · Cornell · PhD
Tried and failed
ex vivo microbial culture metabolic screening applied to cholesterol reduction by gut microbiota. Outcome: no signal. Reason: ex vivo stool cultures failed to reproduce in vivo metabolic conversion to coprostanol
LIPID-DEPENDENT DIET-MICROBIOME-HOST INTERACTIONS · Cornell · PhD
Tried and failed
incorporating in vitro degradation rates into compartmental models applied to whole-organism chemical uptake modeling. Outcome: did not generalise. Reason: in vitro cell culture metabolism rates greatly overestimated in vivo degradation, drastically underpredicting tissue bioaccumulation
Organic carbon-mineral interactions with implications on water reuse and carbon cycling · University of Nevada, Reno · PhD
Lost to a baseline
Conventional static cell cultures fail to replicate dynamic mechanical and biochemical stimuli present in vivo compared to perfusion/rotating bioreactors
The promise of tissue engineering and regenerative medicine in the future of transplant surgery · Boston University · Master's
Considered and rejected
Considered and rejected: Rejected relying on in vitro / cell-culture nanoparticle delivery assays because they poorly predict in vivo delivery in adult animals.
Translational Design of Lipid Nanoparticles (LNPs) to Deliver mRNA Therapies to Solid Tumors and to the Lungs · Georgia Tech · PhD
Considered and rejected
Considered and rejected: Rejected using cultured monocytic cell lines (THP-1, U937) for mechanistic studies because they failed to replicate in vivo monocyte signaling and VEGF splicing.
Control of the collateral formation of cardiovascular disease by SRPK1 · Nottingham · PhD
Considered and rejected
Considered and rejected: Tissue-cultured Mayinga 1976 GP (544I) was rejected from the final outbreak panel because its enhanced infectivity was a cell-culture artifact not representative of circulating wild virus
Investigation and characterisation of viral and host factors that impact intraspecies EBOV infectivity using a viral pseudotyping assay · Nottingham · PhD
Considered and rejected
Considered and rejected: Rejected in vitro immune co-culture killing screen because it would fail to recapitulate full multi-lineage immune surveillance architecture.
Epigenetic contributions to cancer immunosurveillance · Imperial · PhD
Extended passaging, waste buildup, and contamination cause culture instability and loss
Serial subculturing, unpurified media recycling, and high seeding densities resulted in phenotypic drift, cellular senescence, and toxic waste accumulation. Attempts to remediate severe microbial contamination with high antimicrobial concentrations caused fatal cytotoxicity and total culture loss.
Tried and failed
phenotypic differentiation assay using high passage primary cells applied to disease modeling in 3D coculture organoids. Outcome: no signal. Reason: extended serial passaging caused loss of disease-specific phenotypic distinction between cell lines
Modeling T Cell- B Cell Interaction in Rheumatoid Arthritis in a 3D Organoid System · Harvard · Master's
Lost to a baseline
Third biological repeat of LIVE/DEAD functional cell survival assay for both IL-1β and TNF-α time courses was discarded due to cell culture infection causing obscure results
Diabetes-associated Proinflammatory Mediators: The Influence on Tie Receptor Signalling in Endothelial Cells. · De Montfort University · PhD
Tried and failed
high-density in vitro cell culture seeding applied to T-cell enrichment and expansion. Outcome: worse than baseline. Reason: overcrowding and nutrient competition restricted efficient enrichment and growth
Materials to enable and enhance T-cell immunotherapies · Harvard · PhD
Tried and failed
escalating antibiotic and antimycotic treatment concentrations applied to contaminated 3D primary organoid cultures. Reason: failed to eliminate heavy infection and caused cytotoxicity leading to growth cessation or culture loss
Establishing 3D models for the study of intra-tumoural heterogeneity and response to chemotherapy in high grade serous ovarian cancer · Imperial · PhD
Tried and failed
organoid co-culture for disease modeling applied to patient-derived glioma transcriptional states. Outcome: worse than baseline. Reason: suspected genetic drift prevented recapitulation of patient canonical transcriptional meta-programs
Human Brain Organoids for Studying Malignant Cell States and Intercellular Communication in Human Glioma · MIT · PhD
Lost to a baseline
Established organoid culture success rate reached only ~10% (>= passage 5), underperforming the 50% reported by Mullenders et al. (2019) and 70% (>= passage 6) by Lee et al. (2018)
Veränderungen von Expressionsmerkmalen in Blasentumor-Organoiden während Langzeitkultivierungen · Tübingen · PhD
Tried and failed
direct media recycling without supplementation or purification applied to mammalian cell culture. Outcome: worse than baseline. Reason: nutrient depletion and metabolic waste accumulation decreased viable cell density
Recycling and Regeneration of Spent Perfusion Media via Ion Concentration Polarization · MIT · PhD
Tried and failed
serial cell culture passaging applied to primary mammalian fibroblast line maintenance. Reason: loss of cell viability and culture loss due to passaging issues and microbial contamination
Purification of Mammalian Vimentin via the Reassembly of BJ5TAa IF Method · Harvard · Master's
Tried and failed
serial subculturing of anaerobic enrichment cultures applied to chemolithoautotrophic microbial communities. Outcome: no signal. Reason: metabolic activity failed to sustain after transfer into fresh synthetic growth media
Coupled iron reduction-ammonium oxidation (Feammox) in alkaline soils polluted with nitrogen · Saskatchewan · Master's
Lost to a baseline
Cultured adipose endothelial cells from the castrated male mouse cohort were lost due to contamination and rendered unusable for Seahorse metabolic assays
Examining Sex Differences of Adipose Endothelial Cells and the Effects of Foxo1 Deletion · York University · PhD
Considered and rejected
Considered and rejected: Abandoned human intestinal organoid culture after repeated protocol and media modifications failed across four patient tissue preparations, switching to established murine organoids.
Der Einfluss von Teduglutid auf die epitheliale Homöostase im Dünn- und Dickdarm · Tübingen · PhD
Considered and rejected
Considered and rejected: Rejected batch style bioreactors due to accumulation of metabolic waste and inability to maintain cultures for weeks to months.
FODMAP availability modulates the influence of the microbiota on visceral afferent neuron activation · Queen's University · Master's
Two dimensional monocultures fail to sustain differentiated phenotypes and multicellular functions
Isolated monolayer cultures lacked heterotypic interactions and physical cues, leading to phenotypic convergence, attachment loss, and impaired functional responses. Extended 2D passaging also compromised the ability of cells to form organized structures or maintain lineage-specific differentiation.
Tried and failed
single cell type monoculture in vitro applied to spontaneous network bursting on microelectrode arrays. Outcome: no signal. Reason: isolated motor neurons lacked synaptic partners necessary to generate correlated spontaneous firing and bursting
Enrichment for V1 interneurons from mouse embryonic stem cells and evaluation of de novo network formation · UT Austin · PhD
Tried and failed
single-cell-type monoculture assays applied to drug-induced fluid drainage response. Outcome: no signal. Reason: functional response to drug required heterotypic cell-cell interactions present only in co-culture
Tissue-engineered in vitro models for studying lymphatic morphogenesis, pathogenesis, and drug delivery · Cornell · PhD
Considered and rejected
Considered and rejected: Rejected harvesting CN monocultures beyond D50 without astrocyte coculture due to loss of cell attachment and morphology.
Investigating selective neuronal vulnerability in Alzheimer’s and Parkinson’s disease with induced pluripotent stem cells · Oxford · PhD
Tried and failed
2D monolayer cell culture applied to developmental cell phenotype differentiation. Outcome: no signal. Reason: Monolayer culture caused expression profiles to converge, masking differential gene expression present in 3D culture
Characterising embryonic stem cell-derived tenocytes and determining the changing role of scleraxis during tendon development · Cambridge · PhD
Tried and failed
organoid derivation after extended 2D monolayer culture applied to primary cancer cells. Outcome: no signal. Reason: cells maintained in 2D culture for over 24-48 hours lost the capacity to form 3D organoids
Establishing 3D models for the study of intra-tumoural heterogeneity and response to chemotherapy in high grade serous ovarian cancer · Imperial · PhD
Tried and failed
2D monolayer cell culture applied to acidic metabolite cytotoxicity screening. Reason: cells lost 50% viability under physiological lactic acid concentrations unlike 3D tissue models
Tried and failed
2D in vitro cell culture and passaging applied to primary mouse endometrial epithelial cells. Reason: poor cell viability and lack of attachment during passaging
Extracellular matrix hydrogels for endometrial regeneration · Imperial · PhD
Considered and rejected
Considered and rejected: Rejected relying on 2D human myoblast cultures alone for contractile studies, choosing 3D bioengineered microtissues/bundles to enable aligned sarcomeric organization.
Metabolic Reprogramming and Stem Cell Rejuvenation for Skeletal Muscle Regeneration after Aging · University at Buffalo · PhD
Considered and rejected
Considered and rejected: Rejected using 2D monolayer culture to study developmental divergence between adult and fetal tenocytes due to phenotypic convergence/drift.
Characterising embryonic stem cell-derived tenocytes and determining the changing role of scleraxis during tendon development · Cambridge · PhD
Lost to a baseline
Organoid diameter in mesenchyme-free defined culture conditions approached but never matched that of mesenchymal co-culture.
LUNG EPITHELIAL IDENTITY, PLASTICITY, AND FATE CHOICE DURING INJURY REPAIR AND REGENERATION · Penn · PhD
Considered and rejected
Considered and rejected: Rejected conditioned media (indirect co-culture) approaches because proliferation enhancement required direct juxtacrine EC-MuSC contact.
INVESTIGATING VASCULAR ENDOTHELIAL CELL-MUSCLE STEM CELL COMMUNICATION IN SKELETAL MUSCLE IN VIVO AND IN VITRO · Cornell · PhD
Direct co-culture causes spatial disruption, competitive overgrowth, and substrate incompatibility
Mixing multiple cell populations in direct contact caused aggressive cell types to outcompete, overgrow, or physically displace partner cells. Incompatible substrate coatings and spatial constraints further prevented proper cellular integration, domain separation, and monolayer formation.
Tried and failed
multi-node spatial aggregation of mixed neural cultures applied to engineered in vitro neural circuits. Outcome: worse than baseline. Reason: astrocytes exhibited interdigitation instead of domain separation, attenuating long-distance axonal fasciculation across nodes
Tissue Engineered Multi-Aggregate Cortical-Hippocampal Neural Networks for Pharmacological Investigations · Penn · PhD
Tried and failed
prolonged co-culture in matrix-producing host medium applied to microbial co-encapsulation viability. Reason: extended culture or high matrix-former inoculum killed encapsulated partner cells
Functional Materials Grown from Engineered Bacteria · Harvard · PhD
Considered and rejected
Considered and rejected: Single-gel co-culture (mixing organisms in one gel) was rejected in favor of spatially separated printing due to competitive growth between species
Enhancing biomolecule production through microbial engineering and advanced manufacturing · UT Austin · PhD
Considered and rejected
Considered and rejected: Direct co-culture of macrophages with DRG neurons inside microfluidics was rejected due to incompatible substrate coating requirements (PLL only vs. PLL+laminin).
Modelling changes in excitability of the peripheral nervous system using compartmentalised microfluidic culture · Nottingham · PhD
Considered and rejected
Considered and rejected: Rejected initial triple-culture strategy of plating DSEB astrocytes first with mitotic inhibitor AraC due to astrocyte overgrowth and poor neuronal adhesion.
Define the RelationSHIP: INPP5D/SHIP1 regulates inflammasome activation in human microglia · Harvard · PhD
Considered and rejected
Considered and rejected: Rejected 2D direct contact co-culture on Transwell membranes or glass because pericytes outcompete BMECs for surface attachment and physically disrupt monolayer confluence
MODELING THE HEALTHY AND DISEASED BLOOD-BRAIN BARRIER WITH IPSC-DERIVED VASCULAR CELLS · Johns Hopkins · PhD
Tried and failed
seeding aggregates onto preformed stromal cell beds applied to organoid co-culture in hydrogels. Outcome: worse than baseline. Reason: preformed cell bed prevented matrix integration and hindered differentiation
Vascularized, Immune-Infiltrated, and Perfusable Kidney Organoid-on-Chip Models · Harvard · PhD
Tried and failed
sequential dual-layer cell seeding with intervening coating applied to transwell co-culture barrier models. Reason: subsequent extracellular matrix coating and temporary media deprivation caused death of the pre-seeded cell layer
Mesenchymal Stromal Cell Manufacturing for the Identification of Immunomodulatory Properties In Acute Respiratory Distress Syndrome (ARDS) · Georgia Tech · PhD
Considered and rejected
Considered and rejected: Original 3D indirect co-culture (MSCs in insert, spheroids at bottom) was rejected because hMSCs aggregated on PET membranes and spheroids merged into a single necrotic mass.
Conflicting media and supplement requirements compromise co-culture viability
Co-cultured cell populations often required incompatible serum concentrations, growth factors, or specialized basal formulations, leading to compromised morphology and cell death. Suboptimal shared media formulations resulted in nutrient starvation or premature eradication of target cells.
Tried and failed
standard culture medium with generic supplements applied to multi-cell neural transwell co-cultures. Outcome: worse than baseline. Reason: unoptimized astrocyte supplements compromised cell morphology and viability
Regulation of intercellular communication by Alzheimer's disease genetic risk factors · Harvard · PhD
Considered and rejected
Considered and rejected: Pure neuronal cultures for Sholl dendritic analysis were rejected because neurons required serum-free media whereas co-cultured B cells required serum-rich media; reverted to mixed cortical cultures.
BDNF-Producing B Cells Mediate Plasticity in the Recovering Brain After Stroke · UT Southwestern · PhD
Considered and rejected
Considered and rejected: Rejected culture media with 0%, 1%, and 2.5% FBS for FLS co-culture due to observed cell death, poor adhesion, and cell detachment; adopted supplemented Neurobasal medium with 5% FBS instead.
Biomechanical & Biochemical Contributions Of Matrix Metalloproteinases In Joint Pain: Models, Mechanisms, & Patients · Penn · PhD
Considered and rejected
Considered and rejected: Culturing meningeal lymphatic co-cultures in AIM-V (supplemented with VEGF-C and EGF) or Neurobasal media, rejected due to significantly decreased LEC viability compared to Vasculife.
Engineered models of the lymphatic stroma to study cell and fluid transport · Virginia Tech · Doctorate
Considered and rejected
Considered and rejected: Rejected 100% breast cancer media concentration for co-culture studies because 50%/50% breast cancer/osteogenic media provided superior osteoblast viability while maintaining metastatic microenvironment factors.
Investigating Human Cell Influence on the Micromechanical Environment of a 3D-Printed Bone Tissue Model · Virginia Tech · Master's
Considered and rejected
Considered and rejected: Protocols maintaining T cell expansion medium throughout GBO–CAR T co-culture were modified to switch to GBO medium after 24 hours to prevent complete target eradication and accurately model clinical tumor persistence/resistance.
Tried and failed
human plasma-like medium cell culture applied to colorectal cancer cell lines. Reason: failed to sustain cell line growth despite supporting bacterial co-culture
Pharmacomicrobiomics in gastrointestinal cancer: the gut microbiome as modulator of anticancer therapy efficacy and predictor of therapy outcomes · Imperial · PhD
Left open by the authors
Problems the authors named and did not get to.
Left open
Co-culture ROSMAP-derived astrocytes with familial Alzheimer's disease neurons to evaluate non-cell-autonomous astrocyte responses to diseased neuronal environments. Blocker: Requires wet-lab iPSC cell culture and co-culture experimental facilities.
Contribution of SORL1 in human iPSC-derived neurons and astrocytes to Alzheimer’s disease pathogenesis · Harvard · PhD
Left open
Co-culture AKO astrocytes with AKO endothelial cells or neurons in Transwell systems to measure manganese transport, BBB permeability, and neuronal survival. Blocker: Requires wet lab facilities, specific knockout mouse cell lines (AKO astrocytes/endothelial cells), and cell culture apparatus.
THE INS AND OUTS OF MANGANESE: ROLES OF ZIP14 IN BLOOD-BRAIN BARRIER TRANSPORT AND ASTROCYTE FUNCTION · Cornell · PhD
Left open
Deconvolute cell-autonomous versus non-cell-autonomous proteostatic stress effects using pure sorted MNs, interneuron/astrocyte co-cultures, and microfluidic motor unit circuits. Blocker: Requires wet lab facilities, cell culture protocols, microfluidic devices, and biological reagents
Modulating Proteostatic Stress in Human Motor Neurons to Identify Neuroprotective Targets · Harvard · PhD
Left open
Test whether C1q depletion or CD55 inhibition reverses synaptic phenotypes in CLU-deficient triple co-cultures. Blocker: Requires a wet lab with iPSC-derived neuronal, astrocytic, and microglial co-culture platforms and complement inhibition assays.
Regulation of intercellular communication by Alzheimer's disease genetic risk factors · Harvard · PhD
Left open
Investigate signaling dynamics and the effect of INPP5D-deficient microglia on human neurons using co-culture experiments. Blocker: Requires wet-lab facilities for human iPSC differentiation, neuron co-culture, and biochemical signaling assays
Define the RelationSHIP: INPP5D/SHIP1 regulates inflammasome activation in human microglia · Harvard · PhD
Left open
Elucidate the fitness contributions of the cobalamin-dependent gene cluster and Rli47 in Listeria monocytogenes during co-culture with other bacteria. Blocker: Requires wet lab microbiological experiments and co-culture assays with bacterial strains
Exploration of the transcriptomes and functional contributions of Listeria monocytogenes plasmids during food production-associated stress conditions · Iowa State · PhD
Left open
Assess the functionality and lysosomal enzyme composition of axonal versus dendritic autophagic vacuoles using microfluidic isolation chambers. Blocker: Requires a wet lab, primary neuronal cultures, microfluidic devices, and biochemical/microscopy assays.
Compartment-Specific Regulation Of Autophagy In Neurons · Penn · PhD
Left open
Test whether CLU genotype-driven phenotypes in human multi-cell co-cultures depend on an APOE4/4 microglial background versus an APOE3/3 background. Blocker: Requires a wet lab to culture and differentiate human iPSC-derived microglia and co-culture platforms.
Regulation of intercellular communication by Alzheimer's disease genetic risk factors · Harvard · PhD
Left open
Conduct pure and co-culture experiments to validate predicted direct interspecies electron transfer mechanisms. Blocker: Requires a wet lab, microbial strains, and specialized culturing apparatus.
Study of extracellular electron transfer in engineered methanogenic systems · Imperial · PhD
Left open
Perform single-cell RNA-seq on human iPSC-derived neuron, astrocyte, and microglia triple co-cultures across additional individuals. Blocker: Requires wet-lab iPSC differentiation, triple co-culture experimental models, and biological sequencing
Contribution of SORL1 in human iPSC-derived neurons and astrocytes to Alzheimer’s disease pathogenesis · Harvard · PhD
Who has worked on this
Authors of the public theses cited on this page, most-cited first.
- Eliza Atkinson · Imperial · PhD · 2024
Engineering division of labour in Yarrowia lipolytica to relieve the metabolic burden of polysaccharide degradation - Diego Alejandro Hernandez Ospina · York University · Master's · 2024
Study of a Bacterial Coculture for Benzene, Toluene, Ethylbenzene and Xylene Degradation - Alexandra Lish · Harvard · PhD · 2025
Regulation of intercellular communication by Alzheimer's disease genetic risk factors - Falk Ruven Sohl · Tübingen · PhD · 2025
Wiederbesiedlung einer azellularisierten Lebermatrix mit primären porcinen Hepatozyten sowie Kultivierung in einem Bioreaktor - Jennifer Ploski · Imperial · PhD · 2024
Establishing 3D models for the study of intra-tumoural heterogeneity and response to chemotherapy in high grade serous ovarian cancer - Cameron William Michael Murphy · Imperial · PhD · 2023
Investigating the role of chemotaxis in the natural source zone depletion of petroleum hydrocarbons - Vicky Chou · Harvard · PhD · 2022
Define the RelationSHIP: INPP5D/SHIP1 regulates inflammasome activation in human microglia - Hyo Lee · Harvard · PhD · 2022
Contribution of SORL1 in human iPSC-derived neurons and astrocytes to Alzheimer’s disease pathogenesis - Maxine Chan · Imperial · PhD · 2022
Extracellular matrix hydrogels for endometrial regeneration - Yasmin Zoe Paterson · Cambridge · PhD · 2021
Characterising embryonic stem cell-derived tenocytes and determining the changing role of scleraxis during tendon development - Eric Michael Wynne · MIT · PhD · 2025
Recycling and Regeneration of Spent Perfusion Media via Ion Concentration Polarization - Jiaqi Zou · Cornell · PhD · 2025
THE INS AND OUTS OF MANGANESE: ROLES OF ZIP14 IN BLOOD-BRAIN BARRIER TRANSPORT AND ASTROCYTE FUNCTION
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