Age related changes of the extracellular matrix and stem cell maintenance.

Aging is characterized by reduced tissue and organ function, regenerative capacity, and accompanied by a decrease in tissue resident stem cell numbers and a loss of potency. The impact of aging on stem cell populations differs between tissues and depends on a number of non cell-intrinsic factors, including systemic changes associated with immune system alterations, as well as senescence related changes of the local cytoarchitecture. The latter has been studied in the context of environmental niche properties required for stem cell maintenance. Here, we will discuss the impact of the extracellular matrix (ECM) on stem cell maintenance, its changes during aging and its significance for stem cell therapy. We provide an overview on ECM components and examples of age associated remodeling of the cytoarchitecture. The interaction of stem cells with the ECM will be described and the importance of an intact and hospitable ECM for stem cell maintenance, differentiation and stem cell initiated tissue repair outlined. It is concluded that a remodeled ECM due to age related inflammation, fibrosis or oxidative stress provides an inadequate environment for endogenous regeneration or stem cell therapies. Means to provide adequate ECM for stem cell therapies and endogenous regeneration and the potential of antioxidants to prevent ECM damage and promote its repair and subsequently support regeneration are discussed.