A manganese porphyrin-based T1 contrast agent for cellular MR imaging of human embryonic stem cells

Abstract

MRI for non-invasive cell tracking is recognized for enabling pre-clinical research on stem cell therapy. Yet, adoption of cellular imaging in stem cell research has been restricted to sites with experience in MR contrast agent synthesis and to small animal models that do not require scaled-up synthesis. In this study, we demonstrate the use of a gadolinium-free T1 contrast agent for tracking human embryonic stem cells. The agent, MnPNH2, is an easily synthesized manganese porphyrin that can be scaled for large cell numbers. MRI was performed on a 3 T clinical scanner. Cell pellets labeled at different MnPNH2 concentrations for 24 hours demonstrated a decrease in T1 relaxation time of nearly two-fold (P < 0.05), and cellular contrast was maintained for 24 hours (P < 0.05). Cell viability (Trypan blue) and differentiation (embryoid body formation) were unaffected. Cell uptake of Mn on inductively coupled plasma atomic emission spectroscopy corroborated MRI findings, and fluorescence microscopy revealed the agent localized mainly in cell-cell boundaries and cell nuclei. Labeled cells transplanted in rats demonstrated the superior sensitivity of MnPNH2 for in-vivo cell tracking.

Iron (III)-Quercetin Complex: Synthesis, Physicochemical Characterization, and MRI Cell Tracking toward Potential Applications in Regenerative Medicine

“…To avoid this interference, an alternative bright-contrast cell tracking process using paramagnetic T1 contrast agents was applied in preclinical settings. Examples of T1 contrast agents identified as Gd-DTPA (Magnevist, FDA approved) and gadodiamide (Omniscan, FDA approved), as well as manganese porphyrin-based contrast agents, such as MnAMP, MnPNH 2 , and MnEtP, were applied in preclinical settings [ 104 , 110 – 112 ]. Amongst T1 cell-labeling agents, there have been a plethora of approaches based on both gadolinium (Gd) and manganese.…”

Porphyrin as Diagnostic and Therapeutic Agent

“…An in vitro experiment of the DDNP-SPIONs binding to β-amyloid aggregates showed that the combination (DDNP-SPIONs) induced the fluorescence enhancement of the DDNP-SPIONs. The research by Venter et al, 2018 [9], on gadolinium free Mn porphyrin amine as a MRI contrast agent for T1-based cellular imaging and tracking of human embryonic has shown great potential of porphyrins as contrast agents as their study reported on the oncological capabilities of chelated porphyrins.…”

“…Progressive research on porphyrins within these fields has resulted in great scientific and industrial interest in porphyrins, metalloporphyrins, and their related compounds. The bio-application of porphyrins has thus expanded into bio-sensors, fluorescence tracking, in vivo MRI, and PET/CT imaging to photo-immuno-therapy [8,9]. Porphyrins have shown great potential within the medical imaging field (or techniques that create visual representation of the interior of the body for clinical and medical intervention) due to their pharmacological properties such as low toxicity, high tumor uptake, and the possibility of forming complexes with metals.…”

Bright Ferritin—a Reporter Gene Platform for On-Demand, Longitudinal Cell Tracking on MRI

“…This exogenous labeling approach, however, works well only for short-term studies and cannot attain the desired capability for monitoring over the long term. Multiple factors underlie this shortcoming, foremost of which are label dilution upon cell division, leakage of contrast agent from cells ( Venter et al., 2018 ), and non-specific labeling of macrophages that take up contrast agents released from dying cells ( Ma et al., 2015 ). Longitudinal cell tracking requires a method that provides sustained contrast specific to the viable cells of interest.…”