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Quiescence: A Simple and Effective Strategy to Enhance Stem Cell Survival?

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Review of “Quiescence Preconditioned Human Multipotent Stromal Cells Adopt a Metabolic Profile Favorable for Enhanced Survival under Ischemia” from Stem Cells by Stuart P. Atkinson

Low survival and engraftment following cell transplantation into nutrient- and oxygen-deficient injury sites represent important barriers to the success of stem cell-based regenerative therapies [1]. The implementation of a wide range of often complex strategies has led to improvements in cell survival and function [2], although countless laboratories are still on the lookout for simpler and more effective techniques.

Has that search now come to an end? A recent Stem Cells study from the laboratory of Delphine Logeart-Avramoglou (Paris Diderot University, France) has demonstrated that lowering the energy demands of mesenchymal stem cells (MSCs) by forcing them into a quiescent state may be an effective means to address low host nutrient and oxygen levels and,  hence, to improve cell survival and function [3].

Is quiescence the simple and effective strategy the stem cell therapeutics field has been searching for?

Serum deprivation (SD) for 48 hours shifted MSCs into a quiescent state in which cells remained metabolically healthy but non-proliferative with greatly reduced levels of RNA and protein synthesis. Interestingly, this quiescence preconditioning afforded MSCs increased viability under low oxygen and low glucose conditions and, upon reintroduction to standard culture conditions, SD-MSCs exhibited levels of proliferation, protein secretion, and differentiation similar to freshly derived MSCs. Moving in vivo, the study discovered that quiescence preconditioning also mediated enhanced survival and function of MSCs at early time points (one week) post-implantation in mice. 

Subsequent assessments of signaling pathways and metabolic profiling suggested that the inhibition of energy-sensing mTOR signaling, the stimulation of autophagy, and a metabolic shift from oxidative phosphorylation to glycolysis created a metabolic profile adept at withstanding metabolic stress and, in combination, mediated the advantages associated with quiescence preconditioning of MSCs.

This exciting study suggests that the induction of quiescence just might be a simple and effective strategy to enhance cell survival and enhance MSC-based therapeutics. The induced metabolic shift appears to afford MSCs an enhanced stress survival profile while also maintaining the secretion and differentiation profiles necessary for their therapeutic capabilities. This strategy has the potential to lower costs and increase therapeutic outcomes for patients undergoing MSC-based therapeutic treatments; can other stem cell populations also take advantage?

Discussion Points

  • Does stem cells quiescence boost longer-term survival and function?
  • Can quiescent pre-conditioning aid survival in other stem cell types?
  • Are the anti-inflammatory and immunomodulatory functions of MSCs also maintained in the short term?

References

  1. Becquart P, Cambon-Binder A, Monfoulet LE, et al. Ischemia is the prime but not the only cause of human multipotent stromal cell death in tissue-engineered constructs in vivo. Tissue Eng Part A 2012;18:2084-2094.
  2. Patel ZS and Mikos AG. Angiogenesis with biomaterial-based drug- and cell-delivery systems. J Biomater Sci Polym Ed 2004;15:701-726.
  3. Moya A, Larochette N, Paquet J, et al. Quiescence Preconditioned Human Multipotent Stromal Cells Adopt a Metabolic Profile Favorable for Enhanced Survival under Ischemia. STEM CELLS 2017;35:181-196.