Bioengineering strategies to accelerate stem cell therapeutics

Abstract

Although only a few stem cell-based therapies are currently available to patients, stem cells hold tremendous regenerative potential, and several exciting clinical applications are on the horizon. Biomaterials with tuneable mechanical and biochemical properties can preserve stem cell function in culture, enhance survival of transplanted cells and guide tissue regeneration. Rapid progress with three-dimensional hydrogel culture platforms provides the opportunity to grow patient-specific organoids, and has led to the discovery of drugs that stimulate endogenous tissue-specific stem cells and enabled screens for drugs to treat disease. Therefore, bioengineering technologies are poised to overcome current bottlenecks and revolutionize the field of regenerative medicine.

Fig. 1 ∣. Challenges in translating stem cell therapies with potential bioengineered solutions.

a, Present challenges culturing stem cells include maintenance of the stem cell state ex vivo^,,,,- and efficient expansion of naive stem cells^,,,. b, To fully realize the potential of stem cells, reliable protocols for altering cell state must be developed, including differentiation of stem cells to mature cell types^- and reprogramming of somatic cells to pluripotent stem cells^,. c, Conventional cell delivery approaches do not address crucial obstacles in cell transplantation therapies, including maintaining the viability and potency of stem cells during injection^-, providing a supportive microenvironment for the cells after implantation^,-, and controlling the fate of the cells by providing cues to guide regeneration in vivo^,. Engineering approaches are being applied to design materials to address these challenges.

Fig. 2 ∣. Recapitulating niche interactions to direct stem cell fate.

Various biochemical and biophysical factors within the stem cell microenvironment combine to modulate cellular behaviours. Careful design of materials for stem cell culture and transplantation can effectively control matrix properties, such as biochemical composition, mechanics and degradation, as well as soluble factor signalling and cell-cell contact to regulate stem cell fate.

Fig. 3 ∣. Impact of bioengineering on stem cell advances currently in the clinic or on the horizon.

a, b, Hydrogel-based culture systems, such as intestinal organoid cultures, have enabled identification of promising drugs to treat cystic fibrosis^, (a), while others are used to target endogenous stem cells within tissues to restore hearing^, and augment strength^, (b). c, Treatments in clinical trials that could achieve greater efficacy by using engineered scaffolds to culture and transplant cells include ES and iPS cell-derived retinal epithelial cells to restore vision to macular degeneration patients^- and skin grafts of genetically corrected epidermal stem cells to save patients from a deadly skin blistering disease.