Table 4.

Comparison of advantage, disadvantage, and bottleneck of techniques used for increasing the colonization of the lesion area by systemically administered MSCs

Method	Advantages	Disadvantages	Bottleneck
Pretreatment	Easy to perform No need for special equipment	No selective influence on specific cell characteristics The need for in‐depth phenotypical and functional analysis of cells after the procedure	The need for perfect repeatability of the procedure to ensure identical result Susceptible to multitude of environmental factors
Genetic modifications	Selective influence on the expression of a target gene Highly efficient	Low cell survival The risk of insertional mutagenesis Often requires special equipment The use of biological vehicles reduces safety of the procedures and hinders clinical translation	Difficult to maintain the balance between the efficiency of the procedure and the degree of cell damage Requires very solid optimization step Permanent overexpression of a given protein causing unpredictable, long‐term effects
Cell membrane engineering	Low time‐consuming High effectiveness Selective influence on cell properties	Temporal effect of modification	Scarce data from in vivo studies Difficult to select a single antigen to be modified given the complexity of the processes leading to cell homing
Changing the properties of the target tissue	Does not require the selection of a single molecule to drive cell homing Requires only a minimum level of cell modification (e.g., tagging)	Exposes a large area of the recipients’ body to field activity and changes induced thereby Tissue changes may persist long after transplantation and may cause side effects Requires specialized equipment	Maintenance of the balance between the Intensity of the applied field (increasing the inflow of cells) and the degree of tissue exposure to fields’ influence Necessity for careful verification of in vivo effect the field exerts on the tissue