APPLICATION OF NANOPARTICLES IN ISOLATION OF STEM CELLS

Isolation of stem cells from a pool of differentiated cells is a critical step for eventual utilization in any biomedical work. An ideal isolation technique should be quick and easy to

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Table 5.1 Stem cells (SCs) sources [16]

Name

Sources

Advantages

Disadvantages

Embryonic SCs

Inner cell mass of the mammalian blastocyst

Pluripotent, enabling them to form derivatives of all three germ layers

• Results destruction of the embryo, making them an ethically

controversial source

• Form teratomas when transplanted

in vivo, limiting their current clinical value

Hematopoietic

SCs
  • • Bone marrow, umbilical cord, blood, and peripheral blood
  • • Embryonic SCs
  • • Induced pluripotent SCs
  • • Multipotent, can form lymphoid and myeloid blood cells
  • • Extracted in high yields
  • • Readily cryopreserved
  • • Intrinsic tumor- tropic properties

Limited differentiation potential

Mesenchymal

SCs
  • • Fetal origins (Wharton jelly and cord blood)
  • • Developing tooth bud of the mandibular third molar
  • • Adult tissues such as bone marrow and adipose tissue
  • • embryonic SCs
  • • Induced pluripotent SCs
  • • Differentiate into mesenchymal lineages that make up bone, cartilage, fat, and muscle
  • • Readily cryopreserved
  • • Many types are tumor-tropic
  • • Readily genetically manipulated
  • • Limited differentiation potential
  • • Limited yield depending on source

Neural SCs
  • • Brain, spinal cord, and retina
  • • Embryonic SCs
  • • Induced pluripotent SCs
  • • Multipotent, can give rise to neurons, astrocytes, and oligodendrocytes
  • • Tumor-tropic properties
  • • Readily genetically manipulated
  • • Limited differentiation potential
  • • Difficult to source

Continued

Table 5.1 Stem cells (SCs) sources [16]—cont'd

Name

Sources

Advantages

Disadvantages

Endothelial

SCs
  • • Bone marrow
  • • Embryonic SCs
  • • Induced pluripotent SCs
  • • Multipotent, give rise to endothelial precursor cells, which form blood and lymphoid vessels
  • • Readily cryopreserved
  • • Readily genetically manipulated

Limited differentiation potential

Induced SCs

Derived from somatic cells using reprogramming technologies
  • • Can be driven into many different cell types
  • • Creation of patient- specific cell types
  • • Can be made using various viral and nonviral methods
  • • Tumorigenicity poses a considerable clinical hurdle
  • • Heterogeneity in final induced SC population
  • • Technically challenging
  • • Low efficiency of conversion

perform to isolate the stem cells from an assortment of cellular mixtures in a cost-effective manner. Stem cells express unique biomarkers that can be utilized to isolate and purify these cells. Magnetic nanoparticles, including superparamagnetic iron oxide (SPIO) nanoparticles, are most utilized for isolation of stem cells. SPIO nanoparticles, approved for human use by the US Food and Drug Administration, have also been utilized in magnetic resonance imaging (MRI) for enhancing the contrast of cellular targets. These nanoparticles have also been extensively utilized in other biomedical applications, such as isolation and separation of cells and sample preparation [11,12], immunological assays [13], delivery of drugs and genetic material to cells and tissues [14], as well as diseases such as hyperthermia [8].

For isolation of stem cells with magnetic nanoparticles, stem cells first need to be labeled with the nanoparticles. The cells can be labeled either by attaching magnetic nanoparticles to the cell surface, or by internalizing the nanoparticles. The labeled nanoparticles can then be isolated with a combination of flow cytometry and magnetic separation. Magnetic nanoparticles in combination with CD34 antibody have been successfully applied to isolate and enrich peripheral blood progenitor cells from human. Jing et al. [15] reported conjugation of SPIO with CD34 antibody to label CD34+ stem cells. These cells are then isolated from fresh and cryopreserved clinical leukapheresis samples of human blood with a continuous quadrupole magnetic flow sorter (QMS) system. The QMS consists of a flow channel and a quadrupole magnet for cell sorting.

Emerging Nanotechnology for Stem CellTherapy 89

Strategies to promote tumor cell death

Figure 5.1 Strategies to promote tumor cell death: stem cells can be loaded with nanoparticles containing chemotherapy or imaging agents that are released in the vicinity of the tumor, either passively or in response to external stimuli.

The efficacy of this technique has been examined with seven different commercial progenitor cell labeling kits. High cell recovery and enrichment up to 60—69% purity could be obtained. Fig. 5.1 demonstrates strategies for cell-surface or intracellular loading of nanoparticles for stem cell therapy [16].
 
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