Magnetic targeting as a strategy to enhance therapeutic effects of mesenchymal stromal cells

Abstract

Mesenchymal stromal cells (MSCs) have been extensively investigated in the field of regenerative medicine. It is known that the success of MSC-based therapies depends primarily on effective cell delivery to the target site where they will secrete vesicles and soluble factors with immunomodulatory and potentially reparative properties. However, some lesions are located in sites that are difficult to access, such as the heart, spinal cord, and joints. Additionally, low MSC retention at target sites makes cell therapy short-lasting and, therefore, less effective. In this context, the magnetic targeting technique has emerged as a new strategy to aid delivery, increase retention, and enhance the effects of MSCs. This approach uses magnetic nanoparticles to magnetize MSCs and static magnetic fields to guide them in vivo, thus promoting more focused, effective, and lasting retention of MSCs at the target site. In the present review, we discuss the magnetic targeting technique, its principles, and the materials most commonly used; we also discuss its potential for MSC enhancement, and safety concerns that should be addressed before it can be applied in clinical practice.

Recent Progress in Stem Cell Modification for Cardiac Regeneration

“…To date, magnetic particles have been used in several in vitro and preclinical studies [ 80 – 84 ]. However, some safety concerns need to be addressed before wide clinical translation.…”

“…However, some safety concerns need to be addressed before wide clinical translation. In particular, increased iron concentrations can increase the intracellular level of free radicals (in a dose-dependent manner) [ 84 ]. Moreover, the application of strong magnetic fields can have enhancing or inhibiting effects on biological systems or lead to the formation of toxic aggregates from intracellularly located magnetic particles [ 84 – 86 ].…”

“…In particular, increased iron concentrations can increase the intracellular level of free radicals (in a dose-dependent manner) [ 84 ]. Moreover, the application of strong magnetic fields can have enhancing or inhibiting effects on biological systems or lead to the formation of toxic aggregates from intracellularly located magnetic particles [ 84 – 86 ]. In addition, certain limitations should be taken into account when using magnetic nanoparticles for imaging of transplanted SCs: it is difficult to distinguish between magnetized viable and dead cells; and long-term MRI-based follow-up of injected cells is compromised due to the leakage of iron particles or their uptake by macrophages [ 23 , 77 , 87 ].…”

The Potential of Intrinsically Magnetic Mesenchymal Stem Cells for Tissue Engineering

“…Magnetic targeting relies on magnetization of MSCs followed by in vivo targeting with the aid of magnetic fields with the aim to allow and retain the maximum number of cells administered to reach the site of required repair, allowing limitation of the cell number and volume injected [ 58 ]. Typically, this may be with an external magnet [ 59 , 60 ] but increasingly magnetic implants are being developed, as in the orthopedic field where insertion of magnetic scaffolds with or without permanent magnets can be used to aid healing of massive bone defects and chondro-osseous defects [ 61 ]. In vivo guidance of the magnetized MSCs by external static magnetic fields for magnetic targeting can be through the use of permanent magnets or electromagnets, although permanent magnets are likely to be preferred since they are portable, reach higher field strengths compared to electromagnets of similar size, and do not require a power supply or cooling system.…”

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

“…Since the heart is a higly perfused organ, 90 -99% of transplanted cells are typically lost within the first 1 to 2 hours [460][461][462][463][464]. Magnetic cell targeting techniques facilitate guidance of transplanted cells to the site of interest and improve cell retention [465]. For example, magnetic targeting of CDCs led to a 4-fold increase of cell engraftment after injection into ischemic rat hearts [466].…”