Advances and prospect of nanotechnology in stem cells

Abstract

In recent years, stem cell nanotechnology has emerged as a new exciting field. Theoretical and experimental studies of interaction between nanomaterials or nanostructures and stem cells have made great advances. The importance of nanomaterials, nanostructures, and nanotechnology to the fundamental developments in stem cells-based therapies for injuries and degenerative diseases has been recognized. In particular, the effects of structure and properties of nanomaterials on the proliferation and differentiation of stem cells have become a new interdisciplinary frontier in regeneration medicine and material science. Here we review some of the main advances in this field over the past few years, explore the application prospects, and discuss the issues, approaches and challenges, with the aim of improving application of nanotechnology in the stem cells research and development.

Keywords: Nanomaterials; Nanostructure; Nanotechnology; Regeneration medicine; Stem cells.

Figure 1

Establishment of human ESCs (hESCs) showing (a–f) early stages of human embryo development, (g) established hESCs line. In vitro differentiation of hESCs toward hepatocyte-like cells showing (h) hESCs derived embryoid bodies, (i–j) hematopoietic differentiation, (k) endothelia differentiation, (l) neuron differentiation, (m) hepatocytes differentiation, (n) ips cells

Figure 2

Magnetism-engineered iron oxide (MEIO) nanoparticles and effects of their magnetic spin on MRI. a TEM images of MnFe₂O₄ (MnMEIO), Fe₃O₄ (MEIO), CoFe₂O₄ (CoMEIO), and NiFe₂O₄ (NiMEIO). All nanoparticles were synthesized to be ~12 nm with narrow size distributions (0 < ~8%). Scale bar, 50 nm. b Mass magnetization values of MFe₂O₄ nanoparticles. In face-centered cubic lattices of oxygen, the magnetic spins at On sites aligned in parallel with the direction of the external magnetic filed whereas those at Td sites aligned antiparallel. MnFe₂O₄ had the highest mass magnetization value, with a magnetic spin magnitude of 5 μg (ef) T2-weighted spin echo MR images, their color maps and relaxivity (R2) of a series of MEIO nanoparticles at 1.5 T. In f, the R2 of CLIO is also presented, for comparison. Consistent with the mass magnetion results, MnMEIO showed the strongest MR contrast effect (that is, darkest MR image, violet in color map) and had the highest R2 coefficient. Mass magnetization value, MR contrast and R2 coefficient gradually decreased as M2+ changed from Mn²⁺ to Fe²⁺, to Co²⁺ and to Ni²⁺[31]

Figure 3

Various designs of multimodal QD probes. ab Quantum dots having different molecules for target-specific interaction, and, attached to the surface, paramagnetic lipids, and chelators for nuclear-spin labeling. c The silica sphere has QDs and paramagnetic nanoparticles inside and target-specific groups attached to the outside. d The structure of a multimodal QD probe, based on silica-shelled single-QD micelles [40]

Figure 4

TEM images of a FMCNPs b MNPs and c quantum dots. d FMCNPs are aligned in a magnetic field obtained with a fluorescent microscope3. The arrows are added to clearly show the orientation of the magnetic field. The inset image is obtained without a magnetic filed. e Fluorescent microscope image of FMCNPs inside murine ECC stem cells, scale bar: 10 μm [53]

Figure 5

Drawing and transmission electron microscopy (TEM) image (a) and Prussian blue-positive cells (b) showing nanoparticles inside the cell (arrow). c: T2-weighted image of a rat spinal cord injected with nanoparticle-labeled MSCs. Arrowheads mark the injection sites, arrow the lesion populated with cells; Implanted nanoparticles labeled mouse ESCs were labeled with SPIO (eg). Cells were grafted intravenously. In vivo MRI was used to track their fate (h). Prussian blue staining confirmed the presence of iron oxide nanoparticles inside the cells (f). After 4 weeks post-implantation, grafted cells migrated to the lesion site and formed teratomas composed of tissue of all three germ layers (lm); In vitro differentiation of quantum dots labeling of hESCs (d) into neurons (i), hematopoietic cells (j) and endothelia cells (k) [44]

Figure 6

Apoptosis of HEK293 cells induced by SWCNTs. a morphological changes of HEK293 cells cultured with 25 μg/mL SWCNTs for 3 days; a0: showing cells become round and floating with apoptotic characterizatics; control: showing normal morphological cells; a1: showing nodular structure composed of SWCNTs and apoptotic cells; a2: showing apoptotic cells attached by SWCNTs. b1: DNA electrophoresis of cells cultured with 25 μg/mL SWCNTs for 1–5 days, M: molecular Marker; no. 1–5 denote the results of cells cultured for day 1–5, respectively; b2: DNA electrophoresis results of control cells cultured for day 1–5; c: the cell cycle distribution of HEK293 cells cultured with 25 μg/mL SWCNTs for 4 days, the percentage of sub-G1 cells (apoptosis cells) was 43.5% [77]

Figure 7

Schematic diagram depicting the directed growth of MSCs on large-scale carbon nanotube patterns. a patterning of non-polar 1-octadecanethiol (ODT) SAM while leaving some bare Au area. b Selective adsorption and precision alignment of CNTs directly onto a bare Au surface. c Passivation of the exposed bare Au surface between the aligned CNTs with ODT. d Directed growth of MSCs onto the carbon nanotube patterns [85]

Figure 8

a MSC adhesion on various nanostructures and self-assembled monlayer (SAM) on Au or SiO₂ surfaces. MSC spreading was characterized by measuring the cell area in actin filament fluorescence images. The surfaces studied are SWCNTs on Au (SWCNT/Au), SWCNTs on cystamine SAM on Au (SWCNT/Cys), SWCNTs on MHA SAM on Au (CNT/MHA), SWCNTs on APTES SAM on SiO₂ (CNT/APTES), ZnO nanowires on Au (ZNO/Au), V₂O₅ nanowires on cysteamine SAM on Au (V₂O₅/Cys), OTS SAM on SiO₂ (OTS/SiO₂), and APTES SAM on SiO₂ (APTES/SiO₂). b Fluorescence microscope image of actin filaments in MSCs adsorbed onto SWCNT patterns on Au surface. SWCNTs were adsorbed onto bare Au with ODT SAM as passivation layer. c Optical microscope image of MSCs adhered ontp mwCNTs/ODT SAM patterns (50 μm wide mwCNT regions and 100 μm wide ODT regions) with ODT passivation after 24 h of cell culture. The mwCNT regions appear as dark areas around the MSCs. d Elongation of MSCs on bulk swCNT substrates or swCNT line patterns as in (b). e Fluorescence microscope image of vinculins represaenting focal adhesions of MSC adsorbed onto swCNT patterns on Au. f Immunofluorescence image of the fibronectins adsorbed on the swCNT patterns on Au substrate [85]