Reproducibility Crisis, Meet Cell Mimics – A Timely Solution to a Persistent Challenge

Every day, new ideas and innovations bring us closer to breakthroughs in how we diagnose, treat, and potentially cure diseases. Reproducibility, or the ability to replicate a scientific study and get results consistent with previous findings, is fundamental to advancing scientific research. Without reproducibility, scientists can’t verify conclusions, detect errors, or build on what’s already been discovered. Simply put, for scientists to realize the potential of their research, it must be repeatable and consistent.

A Fundamental Issue: Biological Materials are Inherently Variable

But there’s a problem; many studies published in scientific journals cannot be repeated. This lack of reproducibility, dubbed the reproducibility or replication crisis, threatens to slow scientific progress, while also wasting time, money, and resources. The cost of irreproducible data is estimated to be a staggering $28.2B USD and biological reagents and reference materials account for 36.1% of this total¹.

Figure 1. Estimated US preclinical research spend and categories of errors that contribute to irreproducibility (From Freedman et al. 2018¹) .

Fortunately, scientists are working together and devising ways to improve reproducibility in research. It’s a complex problem and while there isn’t a single root cause, the variability of biological materials is a significant factor.

How Biological Variability Impacts Reproducibility

Differences in cell lines, donor-derived materials, reagents, and handling protocols can create inconsistencies from lab to lab, making it difficult to reproduce experimental results. One major contributor to the replication crisis is the use of misidentified or contaminated cell lines—they can skew data, lead to incorrect conclusions, and make replication nearly impossible. Even when researchers follow the same procedures, variability in reagents and materials can cause unexpected failures, leading to wasted time, resources, and research funding^2,3.

Compounding the problem, extended cell culture can result in genetic drift. This can introduce genetic changes that compromise reproducibility and hinder the clinical translation of findings (Figure 2).

Figure 2: Slingshot Biosciences’ scientists performed an experiment using our TruCytes™ CD19 antigen density control to measure CD19 expression in Raji cells over 6 passages. There was a noticeable decrease in CD19 antigen density as early as passage 2.

In the cell therapy space, antigen density on target cells shapes drug potency and effector cell response. Donor material as controls often come with inherent donor-to-donor differences. Factors like age, ethnicity, gender, and more, can influence primary cell behavior and lead to inconsistencies in experimental outcomes.

Precision-Engineered Cell Mimics as a Viable Alternative

Precision-engineered cell mimics are an exciting innovation that can address reproducibility challenges associated with biological materials. These cell mimics replicate the properties of biological cells with unmatched scalability, uniformity, and lot-to-lot consistency. Unlike biological cells, cell mimics demonstrate enhanced closed vial stability (up to 18 months), reducing the need for ongoing maintenance and offering a convenient, cost-effective, off-the-shelf solution. Slingshot Biosciences’ cell mimics are engineered using semiconductor precision, scalability and speed. Compared to biological controls, cell mimics offer significantly higher scalability and lower lot-to-lot variability. For example, in a head-to-head, lot-to-lot comparison of TruCytes™ Lymphocytes Subset Control versus commercially available peripheral blood mononuclear cells (PBMCs), TruCytes™ cell mimics demonstrated significantly less variability, with CVs between 0.1% and 5.7% population percentages, whereas PBMC controls showed CVs ranging from 1.6% to 36.6% . Check out the data in this Application Note.

Table 1: Comparison of biological materials and Slingshot Biosciences’ cell mimics across key parameters such as variability, availability, stability, traceability, and cost.

With a standardized and consistent alternative to biological cells, researchers can achieve more reproducible results within, and across different labs with confidence. Cell mimics have applications in quality control, instrument validation, diagnostics, clinical trial research, and cell therapy development and manufacturing.

Moving Science Forward

While the reproducibility crisis in science is complex and not easily solved, advances like Slingshot Bioscience’s cell mimics are helping to reduce variability and enhance consistency. By implementing these tools, researchers can focus on scientific breakthroughs instead of bottlenecks. It’s time to move beyond the limitations of biological controls and embrace innovations that can make science more reproducible while reducing costs.

Accelerate beyond traditional controls with Slingshot cell mimics. Learn more.

References

1. Freedman LP, Cockburn IM, Simcoe TS. The Economics of Reproducibility in Preclinical Research [published correction appears in PLoS Biol. 2018 Apr 10;16(4):e1002626. doi: 10.1371/journal.pbio.1002626.]. PLoS Biol. 2015;13(6):e1002165. Published 2015 Jun 9. doi:10.1371/journal.pbio.1002165
2. Hughes P, Marshall D, Reid Y, Parkes H, Gelber C. The costs of using unauthenticated, over-passaged cell lines: how much more data do we need? [published correction appears in Biotechniques. 2008 Jan;44(1):47]. Biotechniques. 2007;43(5):. doi:10.2144/000112598
3. Teixeira da Silva JA. Incorrect cell line validation and verification. Ann Transl Med. 2018;6(7):136. doi:10.21037/atm.2018.02.23