Environmental preconditioning rejuvenates adult stem cells' proliferation and chondrogenic potential

Abstract

Adult stem cells are a promising cell source for cartilage regeneration. Unfortunately, due to donor age and ex vivo expansion, stem cell senescence becomes a huge hurdle for these cells to be used clinically. Increasing evidence indicates that environmental preconditioning is a powerful approach in promoting stem cells’ ability to resist a harsh environment post-engraftment, such as hypoxia and inflammation. However, few reports organize and evaluate the literature regarding the rejuvenation effect of environmental preconditioning on stem cell proliferation and chondrogenic differentiation capacity, which are important variables for stem cell based tissue regeneration. This report aims to identify several critical environmental factors such as oxygen concentration, growth factors, and extracellular matrix and to discuss their preconditioning influence on stem cells’ rejuvenation including proliferation and chondrogenic potential as well as underlying molecular mechanisms. We believe that environmental preconditioning based rejuvenation is a simpler and safer strategy to program pre-engraftment stem cells for better survival and enhanced proliferation and differentiation capacity without the undesired effects of some treatments, such as genetic manipulation.

Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section

“…Given the varying stages of degeneration and microenvironments that exist in vivo, it will be important to tailor or design treatments for individuals. One way to achieve this could be to condition stem cells prior to implantation by acclimatizing them to patient specific in vivo microenvironmental milieu, which may include inflammatory cytokines, acidity, oxygen or nutrient deprivation . These treatments must be assessed using appropriate in vitro and ex vivo culture conditions which mimic those of the degenerate niche to assess the likely behavior and survival of transplanted cells prior to progressing to in vivo testing …”

Stepwise preconditioning enhances mesenchymal stem cell-based cartilage regeneration through epigenetic modification

“…In view of the similar phenomena as in our previous studies 11,12 we speculated that the multipotency of MSCs could be modulated by means of epigenetic regulation. Increasing evidences indicate that environmental preconditioning could promote the tolerance of stem cells to adverse post-injection/implantation environment, such as hypoxia and inflammation 21 . Growth factors such as fibroblast grow factor (FGF) composed one of the critical environmental factors shown significant effects on stem cells' rejuvenation including proliferation 22,23 and chondrogenic potential 24,25 .…”

Leaping the hurdles in developing regenerative treatments for the intervertebral disc from preclinical to clinical

“…Culture conditions are also essential to consider during expansion of cells for biobanking of IVD cells for regenerative approaches. Expansion conditions, including passage number, oxygen tension, supplements, and osmolality have been shown to influence the cell phenotype and as such influence the regenerative capacity and differentiation of mesenchymal stromal cells and NP cells . These conditions can be tuned, either to achieve optimal regenerative performance or to achieve an NP phenotype that resembles better the NP cells present within a degenerative niche.…”