Understanding and leveraging cell metabolism to enhance mesenchymal stem cell transplantation survival in tissue engineering and regenerative medicine applications

Abstract : In tissue engineering and regenerative medicine, stem cell-specifically, mesenchymal stromal/stem cells (MSCs)-therapies have fallen short of their initial promise and hype. The observed marginal, to no benefit, success in several applications has been attributed primarily to poor cell survival and engraftment at transplantation sites. MSCs have a metabolism that is flexible enough to enable them to fulfill their various cellular functions and remarkably sensitive to different cellular and environmental cues. At the transplantation sites, MSCs experience hostile environments devoid or, at the very least, severely depleted of oxygen and nutrients. The impact of this particular setting on MSC metabolism ultimately affects their survival and function. In order to develop the next generation of cell-delivery materials and methods, scientists must have a better understanding of the metabolic switches MSCs experience upon transplantation. By designing treatment strategies with cell metabolism in mind, scientists may improve survival and the overall therapeutic potential of MSCs. Here, we provide a comprehensive review of plausible metabolic switches in response to implantation and of the various strategies currently used to leverage MSC metabolism to improve stem cell-based therapeutics. Significance statement: Lack of success of stem cell-based therapies has been largely attributed to the massive cell death observed post-transplantation, which is caused by the metabolic shock these cells experience as they transition from in vitro to a hostile, injured site in vivo. The metabolism in mesenchymal stem cells (MSCs), specifically, is highly sensitive to cellular and environmental cues. In order to improve cell survival rate posttransplantation, it is important that scientists understand, and take into account, the needs and demands of MSC metabolism as they design the next generation of MSC-based therapies.