Tracking embryonic hematopoietic stem cells to the bone marrow: nanoparticle options to evaluate transplantation efficiency

Sean K Sweeney,Nicholas Zavazava,Jose G Assouline,Gohar S Manzar

doi:10.1186/s13287-018-0944-8

Abstract

BackgroundAs the prevalence of therapeutic approaches involving transplanted cells increases, so does the need to noninvasively track the cells to determine their homing patterns. Of particular interest is the fate of transplanted embryonic stem cell-derived hematopoietic progenitor cells (HPCs) used to restore the bone marrow pool following sublethal myeloablative irradiation. The early homing patterns of cell engraftment are not well understood at this time. Until now, longitudinal studies were hindered by the necessity to sacrifice several mice at various time points of study, with samples of the population of lymphoid compartments subsequently analyzed by flow cytometry or fluorescence microscopy. Thus, long-term study and serial analysis of the transplanted cells within the same animal was cumbersome, making difficult an accurate documentation of engraftment, functionality, and cell reconstitution patterns.MethodsHere, we devised a noninvasive, nontoxic modality for tracking early HPC homing patterns in the same mice longitudinally over a period of 9 days using mesoporous silica nanoparticles (MSNs) and magnetic resonance imaging.ResultsThis approach of potential translational importance helps to demonstrate efficient uptake of MSNs by the HPCs as well as retention of MSN labeling in vivo as the cells were traced through various organs, such as the spleen, bone marrow, and kidney. Altogether, early detection of the whereabouts and engraftment of transplanted stem cells may be important to the overall outcome. To accomplish this, there is a need for the development of new noninvasive tools.ConclusionsOur data suggest that multifunctional MSNs can label viably blood-borne HPCs and may help document the distribution and homing in the host followed by successful reconstitution.

Highlights

As the prevalence of therapeutic approaches involving transplanted cells increases, so does the need to noninvasively track the cells to determine their homing patterns
Embryonic stem (ES) cell-derived Hematopoietic progenitor cell (HPC) efficiently uptake mesoporous silica nanoparticles when incubated with cationic protamine sulfate Our laboratories developed a series of protocols for the generation and characterization of HPCs from mouse ES cells
The cells are confirmed as HPCs by their expression of the hematopoietic progenitor cell markers CD41 and CD45 (Fig. 1d), as well as that of the hematopoietic stem cell markers c-Kit and Sca-1 (Fig. 1e)

Summary

Introduction

As the prevalence of therapeutic approaches involving transplanted cells increases, so does the need to noninvasively track the cells to determine their homing patterns. The early homing patterns of cell engraftment are not well understood at this time. Clinical treatment may involve transplant of allogeneic hematopoietic stem cells (HSCs). ES cells can give rise to multipotent HPCs that can generate all hematopoietic lineages upon engraftment while being educated in the host’s own thymus, effectively eliminating the risk for GvHD. These cells are poorly immunogenic and antigenic, giving them an “immuno-privileged” status that precludes immunosuppressive measures normally requisite for regular HSC transplant procedures [3]. Such work highlights the potential for ES cell-derived HPCs in transforming transplantation dynamics by reconstituting a host’s immune system with its own derivatives

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