Emerging Nanotechnology for Stem Cell Therapy
Varun Khurana1, Deep Kwatra3, Sujay Shah2, Abhirup Mandal3, Ashim K. Mitra3
1Nevakar LLC, Bridgewater, NJ, United States; 2INSYS Therapeutics Inc, Chandler, AZ, United States; 3University of Missouri—Kansas City, Kansas City, MO, United States
Contents
- 1. Introduction 85
- 2. Application of Nanoparticles in Isolation of Stem Cells 86
- 3. Application of Nanoparticles in Stem Cell Tracking 89
- 4. Role of Nanotechnology in Regulating Microenvironment of Stem Cells: Potential Roles
in Tissue Engineering 93
- 5. Nanoparticles as Macromolecular Delivery Systems for Stem Cells 96
- 6. Future Prospects and Challenges Facing the Field 100
References 100
INTRODUCTION
Stem cells are specialized cells within tissues that possess two distinct properties of selfrenewal and also the ability to differentiate into a wide variety of cell types with specialized lineages [1]. Their ability to divide into a progenitor cell that does not differentiate further, while simultaneously generating another cell that either differentiates or multiplies into specialized cells gives these cells their “Stem”ness [2]. Stem cells can display different properties depending on their source and timing of collection, and their capabilities to generate different lineages (pluripotent vs. multipotent). Broadly, these cells can be classified as embryonic stem cells and adult stem cells [3]. Embryonic stem cells are usually derived from early animal or human embryos. In a culture with the right conditions, they are capable of multiplying indefinitely and are pluripotent, i.e., giving rise to specialized cells. Adult stem cells or somatic stem cells, on the other hand, are generally multipotent, and capable of generating only a subset of lineages, which are usually restricted to the tissue from which these cells derived.
The capability of stem cells to differentiate into different lineages render these cells attractive candidates in multiple therapies such as injury repairs, tissue regeneration, neurodegeneration, cardiac diseases, osteoarthritis, rheumatoid arthritis, and diabetes. These properties also render these cells candidate for pharmacological and toxicological tests, as well as drug screening tools. Although stem cells hold a lot of promise in the field of regenerative medicine, there are a number of obstacles that limit their utility. Some of
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Emerging Nanotechnologies for Diagnostics, Drug Delivery, and Medical Devices
ISBN 978-0-323-42978-8, http://dx.doi.org/10.1016/B978-0-323-42978-8.00005-X these limitations are moral, ethical, and legal, based on the origin of these stem cells particularly, in the case of embryonic stem cells. Some of these issues can be addressed by utilizing induced pluripotent stem cells, derived from somatic cells possessing characteristics similar to embryonic stem cells [4,5]. There are technical limitations, such as the lack of suitable techniques to efficiently understand and control microenvironment of the stem cells. The signals lead to orderly transduction of targeted transplanted stem cells [5,6]. This retention and short survival rate of transplanted cells in the damaged tissues result in limited utility [7]. Table 5.1 provides a list of stem cells and their scope for the targeted delivery of anticancer therapeutics. Nanotechnology has led to several advancements in stem cell therapy by addressing some of these issues [8].
Nanotechnology refers to the engineering and development of materials, carrier systems, or devices at molecular scale primarily between 1 and 1000 nm in diameter. Although there have been multiple applications of nanotechnology in drug delivery, implants, and medical devices, its utilization in stem cell—based therapies is more recent. With the advent of improved and safer nanomaterials such systems can be applied to medical applications. Simultaneously, there have been advances in the application of stem cells in regenerative medicine along with improvement in techniques for isolation and maintenance of stem cells. As both these technologies have advanced, a better synergy has appeared between the two leading to enhanced nanotechnology-based stem cell therapies [9]. One of the major applications of nanotechnology in the area of stem cell research involves tracking the movement of stem cells that have been transplanted. Another major application of nanotechnology is an improved delivery and targeting of stem cells. Stems cells transplanted by nanocarriers have improved survival rates since these cells are established in safer microenvironment through the release of survivalenhancing biomolecules. A mechanism by which nanoparticles can provide a suitable microenvironment for stem cells is to serve as carriers or cocarriers for biologically active molecules, such as adhesion factors and growth factors. Moreover, nanostructures can improve stem cell transplantation and differentiation. Furthermore, nanoparticle delivery systems can be designed for intra—stem cell delivery of DNA, RNA, siRNA, proteins, peptides, or drug molecules capable of regulating stem cell differentiation [9,10].
In this chapter, we discuss how advances in nanotechnology played a role in enhancing stem cell research, mainly in the terms ofapplication in the isolation and traces ofstem cells. Moreover, regulation ofproliferation/differentiation ofstem cells, intracellular delivery of macro- or micromolecules in stem cells, and their application in tissue engineering and regeneration are described in this chapter.
