Potential role of tracing stem cell transplantation and effects on the immune cell function of ferumoxytol combining with heparin and protamine in vivo/in vitro

Abstract

Cell labeling and tracing have played an increasingly important role in the field of stem cell transplantation. Nanocomplexes combining three Food and Drug Administration (FDA)-approved drugs: heparin (H), protamine (P), and ferumoxytol (F) (HPF nanocomplexes) display high labeling efficiency in human adipose tissue-derived stem cells (hADSCs), but their biological safety has not been determined. In this study, we tested the labeling efficiency of HPF in hADSCs through in vitro cytotoxicity studies and in vivo murine preclinical studies using HPF-labeled hADSCs. The labeling process did not cause cell apoptosis and had little effect on cell proliferation. In vivo magnetic resonance imaging (MRI) showed that the HPF-labeled cells produced a hypointense signal that did not affect liver and kidney functions. However, after injection of HPF-labeled cells into mice, lymphocyte transformation testing showed that T and B lymphocyte proliferation was significantly increased. These findings suggest that extensive safety testing of HPF nanocomplexes is necessary; the process to evaluate HPF as an investigative new drug application could therefore be postponed.

The Story of Ferumoxytol: Synthesis Production, Current Clinical Applications, and Therapeutic Potential

“…Zhao and colleagues conducted a study, finding that implanting HPH‐labeled human adipose tissue‐derived stem cells into the body impacts immune cell function, primarily resulting in a significant increase in T and B lymphocyte proliferation. [ 102 ] This finding suggests that it is necessary to conduct more extensive biosafety tests on HPF nanocomposites. Compared to in vitro labeling, in vivo labeling seems to be safer, as it can avoid some regulatory issues and is more likely to facilitate clinical translation.…”

Recent Progress on Heparin–Protamine Particles for Biomedical Application

“…After pioneering work, fundamental and preclinical studies have been conducted on the clinical use of the heparin–protamine–ferumoxytol cell labeling system for MRI [ 92 , 93 , 94 , 95 ]. A preclinical study optimized the labeling protocol and investigated the efficacy for MRI and the safety/toxicity of this cell labeling system [ 92 ].…”

Chronic Kidney Diseases and Nanoparticle Therapeutics

“…Therefore, drugs are incorporated into nanocarriers and could be used for drug targeting [16]. Nanocomplexes/nanoparticles are also used as kidney disease markers and are therapeutically more feasible [17].…”