Editorial Feature

The Discovery of Stem Cells Through Confocal Microscopes

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The plasticity of embryonic stem cells is widely understood; however, adult stem cells have traditionally been considered less capable of this same characteristic. To confirm whether this assumption is valid, and ultimately to identify any adult stem cells that can be induced into distinct types of cells, researchers have turned to confocal microscopy.

Embryonic vs. Adult Stem Cells

Until recently, embryonic stem cells (ES) were thought to be the only type of pluripotent cells capable of self-renewal, proliferation, and tissue regeneration. Comparatively, adult stem cells have often been considered less superior compared to ES in terms of their regenerative and differentiative potential to the tissues in which they inhabit.

Adult liver cells, for example, can regenerate lost liver tissue following a hepatectomy procedure. Similarly, keratinocyte precursor cells play an active role in wound healing processes. However, neither of these adult stem cells have been shown to have the ability to regenerate tissue outside of their originating location.

Recent advancements in adult stem cell research have determined that these specific stem cells exhibit a greater level of plasticity than previously recognized. In fact, researchers have found that adult stem cells originating from one tissue can contribute to the regeneration of both the tissues in which they reside, as well as other tissues at distal sites.

Applications of Confocal Microscopy for Stem Cell Research

Stem cell biology research has been largely dependent on molecular bioassays, such as Western blots. However, these assays are often limited in their ability to measure the stem cell compartment adequately.

As a result of the inherent limitations associated with these molecular bioassays, researchers have turned to both fluorescence and confocal microscopy techniques to gain a more representative image of the biological complexity of stem cells.

Cardiac Regenerative Medicine

One of the primary goals of cardiac regenerative medical research is to discover adequate ways in which heart failure can be treated prior to deciding that a heart transplant is necessary. To this end, recent advancements in cardiac regenerative medicine have found that a number of different cardiomyocytes, including mesenchymal stem cells (MSCs), cardiac progenitor cells (CPCs) and neural crest-derived stem cells (NCSCs), exhibit an impressive regenerative capacity that can be applied as stem cell therapy for the treatment of severe heart failure.

To fully elucidate the regenerative potential of these cardiomyocyte stem cells, researchers have largely relied on confocal laser scanning microscopy (CLSM). CLSM provides researchers a multidimensional view of stem cells that is not compromised by any potential overlapping signals.

Furthermore, CLSM allows users to easily focus on a specific region of interest within the cell for both in vivo and in vitro sample types. When coupled with a spectral imaging system, CLSM can distinguish between specific wavelengths of the object, thereby reducing the appearance of any non-specific background signals and improving the reliability of this imaging tool.

Hair Follicle Stem Cells

Early work performed by a group of researchers at the University of California San Diego (UCSD) found that hair follicle stem cells containing nestin, which is an intermediate protein filament and neural progenitor cell marker, can bulge out from the hair follicle and differentiate into various neuronal cells including neurons, glia, keratinocytes, smooth muscle cells, and melanocytes.

To confirm these in vitro findings, these researchers utilized confocal microscopy to obtain high-resolution imaging of transgenic mice. By using this microscopy technique, the researchers were able to track the movement of stem cells within the whiskers in real-time. Upon analysis of the obtained images, the researchers determined the fate of some nestin-expressing hair follicle stem cells to ultimately contribute to the formation of the hair follicle sensory nerve.

Sources

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  • Fuira, L., Cicalese, A., Rancati, I., Bianchini, P., Diaspro, A., & Faretta, M. (2010). Stem Cell Biology in Cancer Research. Leica Microsystems. https://www.leica-microsystems.com/science-lab/stem-cell-biology-in-cancer-research/.
  • Fujita, J., Hemmi, N., Tohyama, S., Seki, T., Tamura, Y., & Fukuda, K. (2013). Practical Application of Confocal Laser Scanning Microscopy for Cardiac Regenerative Medicine. InTech. DOI: 10.5772/55864.
  • Duong, J., Mii, S., Uchugonova, A., Liu, F., Moossa, A. R., & Hoffman, R. M. (2012). Real-time confocal imaging of trafficking of nestin-expressing multipotent cells in mouse whiskers in long-term 3-D histoculture. In Vitro Cellular & Developmental Biology. Animal 48(5); 301-305. DOI: 10.1007/s11626-012-9514-z.

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Benedette Cuffari

Written by

Benedette Cuffari

After completing her Bachelor of Science in Toxicology with two minors in Spanish and Chemistry in 2016, Benedette continued her studies to complete her Master of Science in Toxicology in May of 2018. During graduate school, Benedette investigated the dermatotoxicity of mechlorethamine and bendamustine, which are two nitrogen mustard alkylating agents that are currently used in anticancer therapy.

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