UCLA researchers in the Department of Bioengineering at Samueli School of Engineering developed bioengineering approaches that can significantly promote cell reprogramming with higher efficiency. This invention is important for basic science, disease modeling, therapeutic testing, and cell engineering for regenerative medicine applications.

BACKGROUND: Cell reprogramming is a major advancement in biology which is widely applied in regenerative medicine, disease modeling and drug screening. Induced pluripotent stem cells (iPSCs) can be generated from somatic cells by the forced expression of Oct4, Sox2, KLF4 and c-Myc (OSKM) and/or other factors. On the other hand, direct reprogramming is the process of converting one cell type into a very distantly related cell type without proceeding through an intermediate pluripotent stage. However, the reprogramming efficiency is generally low for almost all cell types. To address these needs, we develop bioengineering approaches to enhance the efficiency of cell reprogramming and CRISPR-mediated gene activation.

INNOVATION: This invention involves using an innovative microfluidic device, specific cytoskeletal and adhesion inhibitors, synthetic matrix with well-defined mechanical properties, and three-dimensional (3D) spheroids to significantly promote cell reprogramming with much higher efficiency: (1) microfluidic system applies mechanical squeezing on cells to increase the chromatin accessibility for cell reprogramming; (2) viscoelastic synthetic matrix increases chromatin plasticity; (3) small molecules that reduces the intracellular tension can enhance chromatin accessibility; (4) 3D spheroids of cells can enhance cell reprogramming.

POTENTIAL APPLICATIONS:

• Scientific research tool
• Disease modeling and therapeutic testing
• Cell engineering for regeneration of tissues and therapies

ADVANTAGES:

• A high-throughput device which can process one million cells in one hour.
• 7-fold increase in the reprogramming efficiency compared to the control group.
• Synthetic matrix with well define mechanical properties (stiffness and viscoelasticity)can increase cell plasticity and enhance the efficiency of cell reprogramming
• The 3D niche of spheroids makes the system scalable and adaptable for various cell reprogramming applications.

DEVELOPMENT-TO-DATE: Researchers have demonstrated that the integrated microfluidic, synthetic matrix, and three-dimensional spheroid platform significantly enhances cell reprogramming efficiency in vitro using human and mouse fibroblasts. The system has been validated through quantitative and functional assays.

Related Papers (from the inventors only):

• Song, Y., Soto, J., Chen, B. et al. Transient nuclear deformation primes epigenetic state and promotes cell reprogramming. Nat. Mater. 21, 1191–1199 (2022). https://doi.org/10.1038/s41563-022-01312-3
• Song, Y et al. Biphasic regulation of epigenetic state by matrix stiffness during cell reprogramming. Science Advances 10 (7), eadk0639 (2024). https://www.science.org/doi/full/10.1126/sciadv.adk0639
• Wu, Y et al. Viscoelastic extracellular matrix enhances epigenetic remodeling and cellular plasticity. Nature Communications 16 (1), 4054 (2025). https://www.nature.com/articles/s41467-025-59190-7

Keywords: cell reprogramming, induced pluripotent stem cells, iPSCs, induced neuronal cells, iN cells, microfluidic device, 3D spheroids, lab-on-chip, polydimethylsiloxane, synthetic matrix, regeneration, research tool, small molecules