Table 1.

A comprehensive overview of the current available alternatives to recreate the stem cell microenvironment in vitro for clinical applications.

Component of the native stem cell niche microenvironment	Function in vivo	Corresponding component in vitro	Most recent alternatives
Extracellular matrix (ECM)	Physical adhesion; Cell orientation; Stem cell fate	Scaffolds or matrices (2D or 3D) Coating substrates	Hydrogels [39, 40]; Synthetic peptides (RGD) [73]; Micro- and nanotopographic biomimetic scaffolds [20, 74]
Chemical microenvironment	Provides fundamental nutrients (salts, ions, lipids, etc.); Buffering system	Cell culture medium	Cell-type-specific chemically defined (serum-free) culture medium [75, 76]
	Adhesion factors; Protection from shear forces; Cell proliferation	Fetal bovine serum (FBS)	Human platelet lysates [77]; Human pooled AB serum [78]; Human umbilical cord blood serum [71]; Recombinant human serum albumin [72]; Serum-free (or reduced FBS) culture systems [79]
	Cell proliferation	Feeder cells; Growth factors	Feeder-free systems [44]; Recombinant human growth factors [80]
	Cell metabolism and survival	Oxygen	Bioreactor-controlled oxygen perfusion [51, 81]