Review
Some applications of nanotechnologies in stem cells research

https://doi.org/10.1016/j.mseb.2009.09.018Get rights and content

Abstract

Stem cell based tissue engineering therapies involve the administration of ex vivo manipulated stem cell populations with the purpose of repairing and regenerating damaged or diseased tissue. Currently available methods of monitoring transplanted cells are quite limited. To monitor the outcomes of stem cell therapy longitudinally requires the development of non-destructive strategies that are capable of identifying the location, magnitude, and duration of cellular survival and fate. The recent development of imaging techniques offers great potential to address these critical issues by non-invasively tracking the fate of the transplanted cells. This review offers a focused presentation of some examples of the use of imaging techniques connected to the nanotechnological world in research areas related to stem cells. In particular investigations will be considered concerning tissue-engineered bone, treatment of intervertebral disc degeneration, treatment by human stem cells of muscular dystrophy of Duchenne in small animal models and the repair of spinal cord injuries.

Introduction

Tissue engineering and regenerative medicine are an emerging research area that promises new therapeutic techniques for the repair and replacement of tissues and organs that have lost functions due to ageing, disease, damage, and congenital defects [1], [2], [3]. Clinical applications have already begun to repair a wide variety of tissues, such as blood, skin, cornea, cartilage, and bone.

Imaging techniques are serving an increasingly important role in the rigorous characterization of biomaterial properties and function. Sophisticated 2D imaging technologies have been developed to complement histological evaluation and probe complex biological events occurring at the interface between tissues and biomaterials [4], [5], [6]. However, there is a clear need for high resolution 3D imaging technologies that reveal the spatial distribution of tissues forming within porous biomaterials in vitro and in vivo. Moreover, for regeneration of vascularized tissues such as bone or muscle, the ability to quantify 3D vascular ingrowth would be tremendously valuable, particularly for studies exploring the potential to enhance regeneration via therapeutic angiogenesis strategies [7].

The imaging modality that has been most extensively applied for this purpose, particularly for bone tissue engineering studies [8], [9], [10], [11], is high resolution X-ray computed tomography (CT). CT provides rapid reconstruction of 3D images and quantitative volumetric analysis of X-ray attenuating materials or tissues.

In the perspective of clinical translation of stem cell research, it would be advantageous to develop new techniques to detect donor cells after transplantation to track their fate and thus better understand their role in regeneration of damaged and diseased tissues.

Several groups have reported on successful labeling of mesenchymal pig [12] and mouse embryonic stem cells [13] with nanoparticles of iron oxide (SPIO). These particles are used as contrast agents for magnetic resonance imaging (MRI) [14], [15], [16]. It appears that cells that are able to incorporate SPIO intracellularly are readily detectable with MRI allowing in vivo tracking of such “tagged” cells [17]. MRI can provide a non-invasive and repeated three-dimensional visualization of transplanted “tagged” stem cells in organs, making it particularly attractive for imaging studies [18].

The aim of this review, therefore, is to present some of recent progress obtained by using innovative and non-invasive imaging techniques and nanodiffraction involving nanotechnologies in research areas related to stem cells. In particular, we will provide some examples connected with bone tissue engineering, with treatment of intervertebral disc degeneration, with treatment by human stem cells of muscular dystrophy of Duchenne in small animal models muscle and with the repair of spinal cord injuries.

Section snippets

Studies by X-ray microtomography and nanodiffraction of tissue-engineered bone

Tissue engineering has emerged as a revolutionary approach to the reconstruction and regeneration of lost or damaged tissue such as bone and cartilage [1]. The fundamental premise of tissue engineering is the regeneration of tissues though the implantation of cells/tissues or stimulating cells to grow in an implanted matrix.

Present in the bone marrow stroma, the bone marrow mesenchymal stem cells (MSCs) can give rise to multiple mesodermal tissue types, including bone and cartilage [19], [20],

Study by magnetic resonance imaging of iron oxide labeled stem cells in the intervertebral disc repair

A potential application of stem cell therapy is in the treatment of intervertebral disc (IVD) degeneration, a condition that affects approximately 12 million Americans. Intervertebral disc (IVD) degeneration is a multifaceted, chronic process involving certain detrimental, progressive changes in disc composition, structure, and function occurring faster and/or with greater severity than those associated with normal aging. Such changes characteristic of IVD degeneration may include progressive

3D visualization of human stem cells for muscular dystrophy treatment

Duchenne muscular dystrophy (DMD) is a common X-linked disease characterized by widespread muscle damage that invariably leads to paralysis and death. There is currently no therapy for this disease [42], [43], [44], [45].

Attempts to repair muscle damage in Duchenne muscular dystrophy by transplanting myogenic progenitors directly into muscles are hampered by limited cell survival and the limited migration of donor cells in the muscles. The delivery of myogenic stem cells to the sites of muscle

Magnetic resonance imaging of labeled adult stem cells in the spinal cord repair

Spinal cord injury (SCI) is a severe, often life-threatening and debilitating clinical condition, with an incidence of 40 new cases per million people throughout the world each year, affecting mainly young people with a mean age of 28.6 years [55]. It is characterized by a complex of motor, sensory and autonomic dysfunctions, the degree of which is characteristic for the severity of the SCI.

Stem and progenitor cells from various sources are currently studied for their broad potential use in the

Conclusion

Stem cell based tissue engineering therapies involve the administration of ex vivo manipulated stem cell populations with the purpose of repairing and regenerating damaged or diseased tissue.

Our results showed that for tissue-engineered bone X-ray nanodiffraction provides combined microstructural information about both mineral and organic phases, as was the case for native bone. In particular, an original methodology was proposed very recently for semi-quantitative analysis, allowing the

Acknowledgements

The authors wish to acknowledge the EU Network of Excellence project Knowledge based Multicomponent Materials for Durable and Safe Performance (KMM-NoE) under the contract no. NMP3-CT-2004-502243 and the Program PRIN N2005022411 for financial support.

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