Nanotechnology for Regenerative Medicine: Nanomaterials for Stem Cell Imaging

Aniruddh Solanki; John D Kim; Ki-Bum Lee

Disclosures

Nanomedicine. 2008;3(4):567-578. 

In This Article

Abstract and Introduction

Abstract

Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of microenvironmental signals and novel methods to track and guide transplanted stem cells. The application of nanotechnology to stem cell biology would be able to address those challenges. This review details the current challenges in regenerative medicine, the current applications of nanoparticles in stem cell biology and further potential of nanotechnology approaches towards regenerative medicine, focusing mainly on magnetic nanoparticle- and quantum dot-based applications in stem cell research.

Introduction

The recent emergence of nanotechnology has set high expectations in biological science and medicine; many scientists now predict that nanotechnology can solve many key questions concerning biological systems that transpire at the nanoscale. Nanomedicine, defined broadly as the approach of science and engineering at the nanometer scale towards biomedical applications, has been drawing considerable attention in the area of nanotechnology.[1] Given that the sizes of functional elements in biology are in the nanometer scale range, it is not surprising that nanomaterials interact with biological systems at the molecular level.[2] In addition, nanomaterials have novel electronic, optical, magnetic and structural properties that cannot be obtained from either individual molecules or bulk materials. These unique features can be tuned precisely to explore biological phenomena through numerous innovative techniques. One of the major goals of biology is to address the spatial-temporal interactions of biomolecules at the cellular and integrated systems level.[3] However, to apply nanotechnology to biology and medicine, several conditions must be considered:

  • Nanomaterials must be designed to interact with proteins and cells without interfering with their biological activities

  • Nanomaterials must maintain their physical properties after surface modification

  • Nanomaterials must be nontoxic

Cells are single living units of organisms that receive the input signals from disease and injury and then return the output signals to their microenvironments. Conventional experimental studies for specific cellular responses are typically conducted on large cell populations, which inevitably produce data measured from an inhomogeneous distribution of cellular responses. Unless cellular responses and processes are isolated from inhomogeneous signals at the single cell level, it would be extremely difficult to elucidate the intricate cellular systems and to analyze the complex dynamic signaling transductions. Furthermore, conventional biomedical approaches reveal very little concerning genotypic aspects that transcend into cell phenotypes. Thus, to better understand and control the responses of cells towards external stimuli at the single cell or single molecule level, it is imperative to characterize the full range of cell behaviors (e.g., self-renewal, differentiation, migration and apoptosis).

Recently, stem cells have gained much attention for the treatment of devastating injuries and damage caused by degenerative diseases, diabetes and aging.[4] Stem cells self-renew for long periods of time and then further differentiate into specialized cells and tissues on stimulation by appropriate microenvironmental cues. They are typically categorized as embryonic stem cells (ESCs) or tissue-specific adult stem cells, depending on their origin and differentiation capability. ESCs, which originate from the inner-cell mass of the blastocyst-stage embryo, are able to differentiate into all cell lineages found in the three primary germ layers of the embryo (e.g., endoderm, mesoderm and ectoderm).[5] Although it has been shown that human ESCs (hESCs) can differentiate into many interesting cell types, such as cells of heart, brain or bone,[5] the therapeutic potential of hESCs has not been fully realized owing to numerous restrictions, including biological issues concerning immunogenicity and rejection and social issues concerning ethics and morality.[6,7] Adult stem/progenitor cells (e.g., mesenchymal [MSCs], hematopoietic and neural stem cells [NSCs]) reside in mature tissue compartments and are known to function as the replication resources for cell renewal during normal homeostasis of tissue regeneration. In contrast to ESCs, adult stem cells can only proliferate for a few passages and their differentiation ability is limited to certain cell types, depending on where they are located (e.g., bone marrow, brain or epithelial tissues).[8]

Intrinsic regulators (e.g., growth factors and signaling molecules) and cellular microenvironments, such as extracellular matrices (ECMs), are two prime factors that have critical roles in the regulation of stem cell behaviors. To harness the unique potential of stem cells, it is important to understand the functions of intrinsic regulators and extracellular microenvironments during stem cell fate.[9] Furthermore, to fully achieve the therapeutic promise of stem cells, several critical issues (see "Critical Issues for the Therapeutic Applications of Stem Cells") need to be addressed.

Nanostructures and nanomaterials can interact intrinsically with biological systems at the single molecular level with high specificity. The unique properties of nanomaterials and nanostructures can be particularly useful in controlling intrinsic stem cell signals and in dissecting the mechanisms underlying embryonic and adult stem cell behavior (Figure 1).

Regulation of stem cell fate by microenvironmental signals and the corresponding applications of nanotechnology. ECM: Extracellular matrix.

Herein, we have summarized nanotechnology approaches for stem cell research and have further addressed some of the challenges concerning these research efforts. Owing to the extensive scope of the topic and space limitations, we have focused primarily on cellular imaging from the numerous applications of nanotechnology in stem cell biology.

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