Substrates for clinical applicability of stem cells

Table 1 Benefits and shortcomings of Matrigel, extracellular matrix proteins, synthetic peptides, synthetic polymers and hydrogels

Substrate	Advantages	Disadvantages
Matrigel	Allows feeder-free cell culture	Xenogeneic origin[6]
	Inexpensive	Undefined components[6]
	Long-term hESCs culture[7,8]	Pathogenic contamination risk[4]
		Neu5Gc immunogenic epitope[5]
		Batch-to-batch variability[6]
ECM proteins	See subsections below	Batch-to-batch variability
Vitronectin		Degradation upon sterilization
rhLM-332		Pathogenic contamination risk
LM-E8		Not-Scalable[30]
rh E-cadherins-Fc protein		High production cost[30]
Fibronectin		Immunogenicity risk[17]
Vitronectin	Long-term hESC culture (> 30 passages)[15]	Degradation upon sterilization
	αVβ5 integrin receptor mediated cell attachment[13]	Not-Scalable[16,30]
		High production cost[30]
rhLM-332	High α6β1 integrin affinity[18]
LM-E8	Smaller, easily purified, higher purity vs 780 ku laminins[20]	Not-Scalable[30]
	Better stem cell adhesion than Matrigel and intact laminins[20]	High production cost[30]
	ROCK inhibitor Y-27632 not needed[20]
rh E-cadherins-Fc protein	hESC self-renewal, maintenance and pluripotency comparable to Matrigel™[26]	Low cell adherence vs Matrigel[26]
Synthetic peptides	No batch-to-batch variation[36]	High production costs[47,48]
	Immunogenicity risk avoided[37]	Sterilization difficulties[47]
	Since chemically synthesized	Easily degradable[47]
	Long-term hESCs culture[32,37,44]	Labor intensive cell passaging
		Limited scale-up potential of 2D platform[51]
Synthemax surface	Gamma irradiation sterilization[39]
	2 yr shelf-life[39]
	hESCs cryopreserved and thawed on substrate[38]
	Scalable[38]
	Long-term hESCs culture[38-40]
Synthetic polymers	Inexpensive[45,47]	Limited scale-up potential of 2D platform
PMVE-alt-MA	Easy and rapid fabrication[45,49]
PMEDSAH	Highly manipulable[47]
APMAAm	Long-term substrate stability[46]
Polyacrylates
Chitosan-alginate polymers
(pDTEc) polymer scaffolds
Hydrogels	In-vivo 3D type environment[58]	Difficult to analyze cells embedded in hydrogels
	Thermoresponsive and pH sensitive properties[54,55,58]
(AEtMA-Cl)- DEAEA based		Enzymatic release of cells from hydrogel[57]
PDEAAm-based
HA-based
Alginate-collagen based
PEG-based
PPP-based

hESC: Human embryonic stem cell; ECM: Extracellular matrix; LM: laminins; PMVE-alt-MA : Poly(methyl vinyl ether-alt-maleic anhydride); PMEDSAH: poly[2-(methacryloyloxy)ethyl dimethyl-(3-sulfopropyl)ammonium hydroxide]; APMAAm: Aminopropyl methacrylamide; pDTEc: Poly(desaminotyrosyl tyrosine ethyl ester carbonate); AEtMA-Cl: 2-(acryloyloxyethyl) trimethylammonium chloride; HA: Hyaluronic acid; PDEAAm: Poly(N,N-diethylacrylamide); PEG: Polyethylene glycol; PPP: Platelet poor plasma; 2D: Two dimensional.