Real‐time monitoring and control of soluble signaling factors enables enhanced progenitor cell outputs from human cord blood stem cell cultures
Bibliographic record
Abstract
Monitoring and control of primary cell cultures is challenging as they are heterogenous and dynamically complex systems. Feedback signaling proteins produced from off-target cell populations can accumulate, inhibiting the production of the desired cell populations. Although culture strategies have been developed to reduce feedback inhibition, they are typically optimized for a narrow range of process parameters and do not allow for a dynamically regulated response. Here we describe the development of a microbead-based process control system for the monitoring and control of endogenously produced signaling factors. This system uses quantum dot barcoded microbeads to assay endogenously produced signaling proteins in the culture media, allowing for the dynamic manipulation of protein concentrations. This monitoring system was incorporated into a fed-batch bioreactor to regulate the accumulation of TGF-β1 in an umbilical cord blood cell expansion system. By maintaining the concentration of TGF-β1 below an upper threshold throughout the culture, we demonstrate enhanced ex vivo expansion of hematopoietic progenitor cells at higher input cell densities and over longer culture periods. This study demonstrates the potential of a fully automated and integrated real-time control strategy in stem cell culture systems, and provides a powerful strategy to achieve highly regulated and intensified in vitro cell manufacturing systems.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".