Stem Cell Approaches to Treating Cutaneous Radiation Syndrome

Bojan Milic
March 10, 2015

Submitted as coursework for PH241, Stanford University, Winter 2015

Cutaneous Radiation Syndrome

Fig. 1: An electron microscope image of a mesenchymal stem cell. (Courtesy of R. M. Hunt. Source: Wikimedia Commons)

Since the advent of the nuclear age following the success of the Manhattan Project in 1945, humanity has been faced with the potential threat of exposure to large quantities of ionizing radiation as a result of nuclear warfare, medical accidents, incidents at nuclear reactors, or even acts of terrorism. [1,2] Exposure of human skin to ionizing radiation of doses in excess of 20 Gray (Gy) leads to the development of a serious skin condition referred to as Cutaneous Radiation Syndrome (CRS). [3]

With such high doses of radiation, the vascular system of the affected area of the skin becomes damaged to the point that the affected skin tissue is no longer able to receive sufficient nutrients or levels of oxygen to survive. [4] Not only does the affected tissue become necrotic as a result, but the necrosis spreads to the surrounding (previously healthy) tissue by diminishing the quantity of nutrients and oxygen available to skin adjacent to the necrotic tissue. [3,4] As the symptoms of CRS emerge in a patient and necrosis develops, surgical removal of the affected area (and possibly amputation in the case of the affected skin being located on the limbs) is often necessary to prevent potentially fatal spreading of the necrotic lesion. [3,4]

Stem Cells as a Therapeutic Approach

In recent years, extensive medical research has pointed towards the possibility of implementing a variety of stem-cell-based therapies in treating and managing the development of CRS. [3,4] Here, I provide a brief summary of a few stem cell approaches to treating CRS that are either currently being implemented or may be clinically introduced in the near future.

It is clear that the extent of the damage to skin tissue characteristic of CRS compromises the ability of existing cells to repair and regenerate the damaged tissue. [3,4] The underlying principle of using stem cells in treating CRS is that these stem cells are able to, in essence, compensate for the loss of the regenerative capabilities of the patient's own skin tissue. [3,4] Indeed, bone-marrow-derived mesenchymal stem cells (MSCs), similar to the one depicted in Fig. 1, have already been used to treat CRS patients successfully, either alone or in combination with surgical procedures. [3,4] Understanding the precise molecular mechanisms by which the MSCs act in skin tissue healing and regeneration remains an open question, although recent research suggests that various growth factors and chemokines generated by MSCs are the most likely candidates. [3,4]

Recent research in the minipig model has demonstrated that adipocyte-derived stem cells (ASCs) could be yet another therapeutic avenue to treating CRS. [3,4] Similarly to MSCs, ASCs produce numerous paracrine factors which are, at present, understood to aid the healing of radiation-damaged tissue. [3] One of the key advantages of ASCs is that they can be easily collected from the adipose tissue of the CRS patient, even multiple times if necessary, without adversely impacting the condition of the patient. [3]

Yet another approach to wound healing might involve the use of induced pluripotent stem cells (iPSCs). [4] These iPSCs, which have the capability of differentiating into any other cell type, can be generated by reprogramming differentiated cells using as few as 3 or 4 factors (first demonstrated using the Yamanaka factors, namely Sox2, Oct4, Klf4, and c-Myc). [5] However, much work remains to be done in understanding how to control the differentiation of these cells to avoid uncontrolled growth leading to cancer before the use of iPSCs can be considered in clinically treating CRS patients. [4]

© Bojan Milic. The author grants permission to copy, distribute and display this work in unaltered form, with attribution to the author, for noncommercial purposes only. All other rights, including commercial rights, are reserved to the author.


[1] B. Milic, "Symptomatic Development of Acute Radiation Syndrome," Physics 241, Stanford University, Winter 2015.

[2] J. Lee, "Acute Radiation Syndrome," Physics 241, Stanford University, Winter 2012.

[3] D. Riccobono et al., "Application of Adipocyte-Derived Stem Cells in Treatment of Cutaneous Radiation Syndrome," Health Phys. 103, 120, (2012).

[4] R. Tamarat et al., "Stem Cell Therapy: From Bench to Bedside," Radiat. Prot. Dosimetry 151, 633, (2012).

[5] K. Takahashi and S. Yamanaka, "Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors," Cell 126, 663, (2006).