**1. Introduction**

Stem cells reside within a specific extracellular microenvironment, which consists of a com‐ plex mixture of soluble and insoluble, short- and long-range signals [1]. Extracellular matrix (ECM) to which stem cells adheres is one of the microenvironmental parameters regulated stemcell fates [2–4]. Once moving outside of their niche, stem cells will quickly lose their develop‐ mental potential, which limits the application of stem cell therapy [5]. Besides, mounting evidence on stem cells and their niche indicates that transplanted stem cells are unable to survive and

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adapt atthe siteof administrationwhere there is lackoffunctionalvascularnetworktotransport blood, supply oxygen and nutrients, and remove metabolites [6].

Through enhancing cell retention and engraftment after transplantation, modulating stem cell fate, and promoting functional vasculature formation, co-transplantation stem cells with natural or synthetic ECM that mimic natural extracellular milieu could be a potentially powerful tool to break the current bottleneck and maximize the effectiveness of stem cell therapy [7–9]. These strategies provide considerable hope for the development of stem cell therapy in degenerative diseases. This chapter will provide the insights into the interaction between stem cells and ECM, as well as current knowledge and involvement of stem cell therapy. Moreover, we will discuss the strategy of co-transplantation stem cells and ECM for tissue regeneration with enhanced therapeutic efficacy.
