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Page 2 of 14 Velasquillo et al. Plast Aesthet Res 2020;7:31 I http://dx.doi.org/10.20517/2347-9264.2020.30

INTRODUCTION
According to the National Cancer Institute, degenerative disease is a pathology in which the function or
[1]
structure of the affected tissues or organs worsens over time . Unfortunately, neither most degenerative
diseases nor craniofacial congenital malformation diseases have a cure, so they evolve until patients
become severely disabled. Since stem cells became an alternative treatment, they have changed the course
of these diseases. Their applications are currently being tested and have shown positive results in several of
these diseases.

Stem cells are cells with self-renewal and differentiation abilities. Mesenchymal stem cells (MSC) are adult
stem cells that are not hematopoietic and can be found in several tissues, such as adipose tissue, bone
marrow, and umbilical cord, to mention some examples. According to the International Society for Cell
Therapy (ISCT), MSC must (1) be plastic-adherent; (2) express CD105, CD73, and CD90; (3) lack CD45,
[2]
CD34; and (4) differentiate into osteoblasts, adipocytes, and chondroblasts ; however, these criteria do
[3]
not suffice to justify their therapeutic potential . Besides their differentiation ability, MSC have paracrine
[4,5]
activity in angiogenesis, cellular activation/proliferation, and immunomodulation . Since they were first
introduced in 1970 by Friedenstein, MSC have changed the treatment of individuals with orthopedic,
hematologic, oncologic, ophthalmologic and dermatologic conditions. They have been used mainly to
replace cell lines that have been lost or destroyed or to modify the behavior of other cells.

In this paper, we will briefly describe the applications of MSC in common degenerative and congenital
diseases in Mexico.

DEFINING THE REGENERATIVE POTENTIAL OF MSC BEYOND BIOLOGY
For many years, the use of autologous cells isolated directly from biopsies was the only alternative for tissue
engineering applications. Fully differentiated cells tend to lose cellular features if they are exposed to a
constant cellular division. These cellular features include changes in the extracellular matrix (ECM), protein
synthesis, altered metabolism, and dedifferentiation. Regenerative therapies commonly need a high number
of cells, leading to the search of cells with high regenerative potential and no risk of morphological features
loss. Mesenchymal stromal cells have become a promising alternative since they are one of the first cells in
[3]
cellular lineage with unlimited fashion propagation and an extensive differentiation ability .

The analysis of the potential of MSC for therapeutic purposes can be conducted at different stages.
Typically, the mesenchymal phenotype according to the ISCT criteria should be verified; however,
additional surface markers have been described, which include being positive for CD29, and negative
for CD14, CD11b CD19, CD79 alpha, and HLA-DR surface markers. Differentiation protocols can
also be analyzed based on the expression of these markers in chondrogenic, adipogenic, or osteogenic
lineages. For example, osteogenic differentiation can be confirmed with alkaline phosphatase activity,
calcium release after osteogenic stimulation, catalase (osteoclast inhibitor), and glutathione peroxidase 3
[6]
(osteogenic biomarker) expression . Transcriptional analysis at mRNA levels is another alternative to track
the therapeutic potential of MSC. It is possible to estimate cellular growth and colony-forming potential
quantifying the MSC marker STRO-1 and the platelet-derived growth factor receptor A (PDGFR-alpha). A
transcriptional increase of Twist-related protein-1 (TWIST-1) and Twist-related protein-2 (DERMO-1) has
[7]
also been described as crucial for MSC growth and development .

There has been a continuous debate about whether autologous or heterologous cells are the most adequate
source of MSC in regenerative therapies for congenital and craniofacial diseases. Their immunomodulatory
ability is a relevant aspect exerted through the inhibition of T-cell proliferation, which regulates the
immune response, and is also involved in the alloimmune response. Autologous MSC have been shown
to decrease in vitro alloimmune response in host autologous cells in transplanted murine models. It has