Biomedical Engineering Reference
In-Depth Information
result of a prolonged inflammatory phase. This has propelled scientists to look toward the
highly complex integumentary system, made up of numerous stem-cell populations and
matrix components, to play a vital role in skin development and repair [8].
Skin procurement and grafting has been an area of interest since 1869 when Jacques-
Louis Reverdine performed the first successful “fresh” skin allograft [9]. Skin allografting is
a tissue transplant technique where skin is taken from a cadaver and placed into a recipient
[10]. Autografting uses the same technique, but takes tissue from other parts of the patient's
body. Though both techniques are still readily used, associated significant drawbacks make
these treatments less than ideal. Allografts carry immunogenic risks associated with the
implantation of foreign tissue, while autografts carry risks of donor site morbidity and
require the creation of a secondary surgical site [10].
Adult Stem Cells for Skin Regeneration
Tissue engineering provides an alternative treatment method that utilizes the skin's regener-
ative properties in combination with cells and biomaterials to regenerate tissue. Adult stem
cells are an attractive cell source for skin regeneration due to the variety of cells that make
up skin tissue. Ideally, stem cells would be able to differentiate into different cell types,
resulting in complete healing of the skin. Stem cells, with the unique ability to self-renew
and differentiate, provide the basis for stem-cell-based therapies. Stem cells give rise to func-
tion-specific daughter cells, which are genetically identical to the parent cell and thus can be
used to multiply and form colonies to help grow new tissue. In recent experiments, Hocking
and Gibran, along with Chen and associates have suggested that the secretion of diffusible
proteins (also known as paracrine factors or growth and differentiation factors), is the
major mechanism by which stem cells enhance repair. Mesenchymal stem cells (MSCs),
adipose-derived stem cells (ASCs) and epithelia stem cells have all been studied for skin
tissue engineering applications.
Mesenchymal Stem Cells
Mesenchymal stem cells are found throughout the body and have been found to move away
from their initial cell niche to other parts of the body to aid in tissue repair. The hallmark
characteristic of MSCs is their ability to differentiate towards chondrogenic, adipogenic,
and osteogenic lineages. They have, however, been shown to be capable of differentiating
towards other cell types, such as neuronal, epithelial, and muscle cells [11]. Found in bone
marrow, adipose tissue, nerve tissue, umbilical cord blood, and dermis, MSCs have a plasticity
that does not induce immunoactivity in the host, making the cells an important building
block in cell therapy [12]. In a study by Chen and associates, bone-marrow-derived alloge-
neic MSCs injected into mice cutaneous wounds, were shown to express keratinocyte-specific
proteins and contributed to the formation of glandular structures after injury. The specific
role of exogenous MSCs in healing was studied by direct application of MSCs into the
wound bed [13]. Healing of full thickness wounds in normal and diabetic mice were
significantly improved with the application of MSCs. Though the number of grafted MSCs
declined, proliferative and angiogenic signals, Wnt3a, Vascular endothelial growth factor
(VEGF), and Platelet-derived growth factor receptor α (PDGFRα), remained high, implying
the recruitment of endogenous cells in healing [13]. In another study, it was found that media
taken from bone-marrow MSC cultures were rich in a vast number of cytokines. This MSC-
conditioned medium when applied to wounds, in the absence of exogenous cells, accelerated
wound healing, thus emphasizing the importance of secretory factors of MSCs [14].
