Table 3.

Overview of modification techniques

Modification strategy	Advantages	Disadvantages
MSCs for drug delivery	Easily performed in culture	Short cell life after engraftment
	GMP grade existing drugs more readily available	Drug effects on stem cell itself
		Not possible to load all drugs
		Required short interval between loading and administration
Anti-microbial enhancement	Allows specific targeting of identified pathogens	Of less relevance outside infectious disease
Licensing strategies	Rely on endogenous mechanisms	Full licensing environment difficult to recreate
	Proven cryopreservation compatibility
Hypoxia priming	Enhances cell proliferation during manufacture as well as efficacy	Requires specific manufacturing equipment
Differentiation prior to engraftment		Can be long and difficult manufacturing process
Gene modifications	A wide range of possible therapeutic proteins can be expressed	Unpredictable effects of transgene on stem cell
		Risk of stem cell mutagenesis with some vector options
Small molecule priming	Inexpensive and simple methodology	Possible off-target effects on MSC
	Wide availability of GMP compounds
EV enhancement	Increased safety / lower immunogenicity due to no cell involved	Heterogeneity within EV batches due to culturing and isolation methods
	Easier storage and delivery of therapeutic	Large scale production still problematic