In serum veritas—in serum sanitas? Cell non-autonomous aging compromises differentiation and survival of mesenchymal stromal cells via the oxidative stress pathway

Abstract

Even tissues capable of complete regeneration, such as bone, show an age-related reduction in their healing capacity. Here, we hypothesized that this decline is primarily due to cell non-autonomous (extrinsic) aging mediated by the systemic environment. We demonstrate that culture of mesenchymal stromal cells (MSCs) in serum from aged Sprague–Dawley rats negatively affects their survival and differentiation ability. Proteome analysis and further cellular investigations strongly suggest that serum from aged animals not only changes expression of proteins related to mitochondria, unfolded protein binding or involved in stress responses, it also significantly enhances intracellular reactive oxygen species production and leads to the accumulation of oxidatively damaged proteins. Conversely, reduction of oxidative stress levels in vitro markedly improved MSC function. These results were validated in an in vivo model of compromised bone healing, which demonstrated significant increase regeneration in aged animals following oral antioxidant administration. These observations indicate the high impact of extrinsic aging on cellular functions and the process of endogenous (bone) regeneration. Thus, addressing the cell environment by, for example, systemic antioxidant treatment is a promising approach to enhance tissue regeneration and to regain cellular function especially in elderly patients.

Microenvironmental Views on Mesenchymal Stem Cell Differentiation in Aging

“…No other uses without permission. jdr.sagepub.com Downloaded from decreased adipogenic differentiation (Geissler et al 2013). In addition, after being treated with conditional media from young PDLSCs, aged PDLSCs demonstrate enhanced proliferation and differentiation capacities as well as promoted tissue-regenerative capability in vivo (Zheng et al 2009).…”

Autologous Platelet-Rich Plasma: A Biological Supplement to Enhance Adipose-Derived Mesenchymal Stem Cell Expansion

“…Cell expansion requires a basal medium supplemented with proteins, growth factors, and enzymes to support cell attachment and proliferation. Classical protocols use culture media supplemented with xenogeneic additives (e.g., fetal calf serum or fetal bovine serum [FBS]), 14,15 which present a potential risk of infection and immunological reaction. To reduce these risks, efforts are devoted toward the development of human allogeneic supplements (e.g., human serum, human platelet derivatives).…”

Biomaterials based strategies for skeletal muscle tissue engineering: Existing technologies and future trends

“…2D), which isolate and protect the cells from the host immune system, while at the same time allowing the outward diffusion of factors secreted by the encapsulated cells [79]. An additional issue associated with the use of MSCs is the decline in its regenerative properties with age [80,81], which is further compromised with in vitro expansion [82]. These raise questions about the efficacy of autologous cell-based approaches especially in elderly patients.…”