Harnessing conserved signaling and metabolic pathways to enhance the maturation of functional engineered tissues

Neal I Callaghan; Lauren J Durland; Ronald G Ireland; J Paul Santerre; Craig A Simmons; Locke Davenport Huyer

doi:10.1038/s41536-022-00246-3

Harnessing conserved signaling and metabolic pathways to enhance the maturation of functional engineered tissues

NPJ Regen Med. 2022 Sep 3;7(1):44. doi: 10.1038/s41536-022-00246-3.

Authors

Neal I Callaghan^{1

2

3}, Lauren J Durland^{4

5}, Ronald G Ireland^{4

6}, J Paul Santerre^{4

6

7

8}, Craig A Simmons^{4

6

8}, Locke Davenport Huyer^{9

10

11}

Affiliations

¹ Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, M5G 1M1, Canada. [email protected].
² Institute of Biomedical Engineering, Faculty of Applied Science and Engineering, University of Toronto, Toronto, ON, M5S 3G9, Canada. [email protected].
³ Faculty of Medicine, Dalhousie University, Halifax, NS, B3H 2Y9, Canada. [email protected].
⁴ Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, M5G 1M1, Canada.
⁵ Department of Molecular Genetics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.
⁶ Institute of Biomedical Engineering, Faculty of Applied Science and Engineering, University of Toronto, Toronto, ON, M5S 3G9, Canada.
⁷ Faculty of Dentistry, University of Toronto, Toronto, ON, M5G 2L3, Canada.
⁸ Department of Mechanical and Industrial Engineering, Faculty of Applied Science and Engineering, Toronto, ON, M5S 3G8, Canada.
⁹ Department of Applied Oral Sciences, Faculty of Dentistry, Dalhousie University, Halifax, NS, B3H 4R2, Canada. [email protected].
¹⁰ School of Biomedical Engineering, Faculties of Medicine and Engineering, Dalhousie University, Halifax, NS, B3H 4R2, Canada. [email protected].
¹¹ Department of Microbiology & Immunology, Faculty of Medicine, Dalhousie University, Halifax, NS, B3H 4R2, Canada. [email protected].

Abstract

The development of induced-pluripotent stem cell (iPSC)-derived cell types offers promise for basic science, drug testing, disease modeling, personalized medicine, and translatable cell therapies across many tissue types. However, in practice many iPSC-derived cells have presented as immature in physiological function, and despite efforts to recapitulate adult maturity, most have yet to meet the necessary benchmarks for the intended tissues. Here, we summarize the available state of knowledge surrounding the physiological mechanisms underlying cell maturation in several key tissues. Common signaling consolidators, as well as potential synergies between critical signaling pathways are explored. Finally, current practices in physiologically relevant tissue engineering and experimental design are critically examined, with the goal of integrating greater decision paradigms and frameworks towards achieving efficient maturation strategies, which in turn may produce higher-valued iPSC-derived tissues.

Publication types

Review