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

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.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0944-8) contains supplementary material, which is available to authorized users.

Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model

“…Of the 1694 articles identified in Scopus, after screening, 771 articles were excluded (416 reviews, 106 publications before 2000, 50 publications in other languages, and 199 duplicated in Pubmed search), and after assessing eligibility, 910 articles were excluded (287 reported no data about HSC and 623 reported no data about noninvasive imaging); thus, only 13 articles were included from this database. In total, only 21 nonduplicate full text articles were included in this review [9,11,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34], as depicted in Figure 1.…”

“…The hematopoietic stem cell (HSC) extraction and isolation process used in the selected studies is described in detail in Table 1. Of the 21 selected studies, nine (43%) [16,[18][19][20]23,25,28,32,34] studies used mice as a cell donor for bone marrow transplant (BMT), seven studies (33%) used humans as a cell donors [9,11,21,24,26,27,33], two studies (10%) used rat cells [29,30], and the remaining studies used other cell donors, such as fish [17], axolotl [22], and dogs [31], corresponding 5% for each study. Regarding the source of the cells, the majority of studies (53%) [16,[18][19][20]23,25,[28][29][30][31][32] used bone marrow; however, the study by Ushiki [25] used bone marrow and spleen cells, and the second main source of cells was the umbilical cord used in five studies (24%) [9,11,24,27,33], followed by peripheral blood, which was used in two studies (10%) [21,26].…”

“…Regarding the source of the cells, the majority of studies (53%) [16,[18][19][20]23,25,[28][29][30][31][32] used bone marrow; however, the study by Ushiki [25] used bone marrow and spleen cells, and the second main source of cells was the umbilical cord used in five studies (24%) [9,11,24,27,33], followed by peripheral blood, which was used in two studies (10%) [21,26]. Furthermore, the study by Lopes [22] used liver and spleen cells, the study by Astuti [17] collected the renal marrow cells from zebrafish, and the study by Sweeney [34] obtained cells from embryonic cells. Of eleven studies that used rodents as cell donors, the age of the animals was, on average, 8 weeks [18,20,23,25,30], ranging from 6 [18] to 10 [20] weeks, and the use of male rodents [29][30][31][32] was more prevalent than of female rodents [18], though two studies [23,28] used both genders.…”

“…The main method used for harvesting stem cells from animals in the selected studies was flushing (29%) [18,29,30,32], followed by maceration (21%) [22,23,28]. The other studies reported the methods of differentiation from embryonic cells [34] and femoral bone marrow aspiration in live animals [31]. Of the studies that used humans as cell donors, only one study [26] reported the apheresis method for harvesting stem cells.…”

“…To study the dynamics of hematopoietic reconstitution, in which cells localize deep inside hematopoietic organs and other tissues, different modalities of molecular imaging are used for HSC tracking and engraftment, such as (i) optical imaging represented by bioluminescence imaging (BLI) [9,11,[16][17][18][19][20] and fluorescence imaging (FLI) [21][22][23][24][25], (ii) nuclear imaging represented by positron emission tomography (PET) [26][27][28] and single-photon emission computed tomography (SPECT) [29][30][31], and (iii) magnetic resonance imaging (MRI) [32][33][34].…”