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Controlling Stem Cells with an Engineered DNA Culture System

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Review of “Instructing cells with programmable peptide DNA hybrids” from Nature Communications by Stuart P. Atkinson

The extracellular matrix (ECM) that surrounds stem cells represents a dynamic and heterogeneous environment and plays a significant role in controlling cell fate [1, 2]. An in vitro tunable ECM matrix for stem cell culture may enable the detailed study of stem cell interactions and may permit the production of enhanced biomaterials displaying ECM-like characteristics for regenerative purposes. Now, researchers from the lab of Samuel I. Stupp (Northwestern University, Chicago, USA) report that engineered DNA strands may represent the means to achieve such a culture system [3]!

The system designed by Freeman et al. consists of immobilized DNA surface strands and complementary bioactive strands, which are fused to ECM protein/peptide factors such as mitogens or cell surface receptors. The system is deemed to be “on” when the complementary surface and bioactive strand bind to each other, while the addition of a targeted single stranded (ss) DNA strand or enzyme can disrupt DNA strand binding and switch the signal to “off” and regenerate the surface strand for another signal. Additionally, the strands can be designed to switch “off” (i.e., separate) in response to differing ssDNA stimuli, so allowing the presence of more than one bioactive strand and thereby offering a highly dynamic and tunable ECM system.

The authors tested their engineered ECM system with neural stem cells (NSCs) and two different surface strands; one displaying an NSC-differentiation enhancing factor and the other displaying an NSC-proliferation enhancing factor. Excitingly, NSCs neurospheres migrated away from each other when exposed to the ECM surface expressing the differentiation enhancing factor, but regathered as this signal was switched off.

The authors note that their system should facilitate the study of stem cell:niche interactions and provide a starting point for the generation of “rationally designed dynamic regenerative biomaterials” that may aid the production of functional and transplantable tissue constructs. Stay tuned to the Stem Cells Portal to discover the future fate of this exciting new technology!

References

  1. Frantz C, Stewart KM, and Weaver VM. The extracellular matrix at a glance. J Cell Sci 2010;123:4195-4200.
  2. Hynes RO. The extracellular matrix: not just pretty fibrils. Science 2009;326:1216-1219.
  3. Freeman R, Stephanopoulos N, Alvarez Z, et al. Instructing cells with programmable peptide DNA hybrids. Nat Commun 2017;8:15982.