Table 3 Overview of modification techniques

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