Stem cells are a unique population of undifferentiated biological cells that have the capacity to self-renew and differentiate into different cell types. They play a central role in the field of regenerative medicine, aimed at the repair and replacement of diseased cells, tissues and organs through the transplantation of healthy cells and tissues; in particular, stem cells [1
]. Plastic surgery shares several of the same principles with regenerative medicine, historically functioning on a more macroscopic level by using a patient's own tissue to restore and enhance the body. As our understanding of cellular regenerative therapies progresses, plastic surgeons may soon have the option of utilizing a single autologous cellular source for the regeneration of different tissue types.
There are several different types of stem cells that have been considered for clinical applications. Embryonic stem cells (ESCs) have the greatest regenerative "potential" being that they are naturally pluripotent and can differentiate into all adult cellular types. The successful isolation and culture of human ESCs has allowed investigators to gain a much better understanding of the capabilities of these cells to regenerate different tissue types [2
]. ESC research, however, has been restricted by controversy surrounding the origin and isolation of these cells. Additional obstacles include safety concerns over potential tumorigenicity [3
] and immunocompatibilty [4
]. These issues, as well as the ethical barriers have significantly limited the clinical applicability of ESCs at this time.
Adult stem cells such as mesenchymal stem cells (MSCs) circumvent many of the ethical and technical issues associated with ESCs as they can be isolated from developed tissues including bone marrow, fat, and skin (bone marrow stromal cells [BMSCs], adipose tissue-derived stem cells [ADSCs], and adult skin stromal cells [ASSCs], respectively) [5
]. However, these cells are multipotent, and are therefore restricted to the cell lineage in which they reside. Regardless, adult stem cells are a highly useful cell population in regenerative medicine as their ease of isolation, multilineage differentiation, and potential for autologous transplantation makes them a favorable candidate for clinical translation.
The creation of induced pluripotent stem cell (iPSC) lines, or adult somatic cells reprogrammed into pluripotent cells, has allowed researchers to utilize the differentiation capabilities of ESCs, while avoiding the ethical issues associated with ESC isolation. iPSCs share many similar properties with ESCs including expression of certain stem cells genes and proteins, chromatin methylation patterns, potency and differentiability [6
]. Importantly, iPSCs can be created from several different, easily accessible cell types [7
]. However, clinical translations of iPSC therapies still have noteworthy challenges. Generation of iPSCs has a low reprogramming efficiency [11
] and requires the introduction of exogenous transcription factors with viral vectors [6
] or through other significant ex vivo
manipulations of cells [12
]. This process has led to concerns over the stability of these cell lines [14
] and the possibility of chromosomal aberrations [15
], preventing safe use in human trials currently.
ADSCs have recently been investigated as a source of multilineage precursor cells [16
], and are particularly promising for regenerative therapies as they can be easily harvested with minimal donor site morbidity [17
]. In addition, ADSCs have a differentiation potential similar to other MSCs as well as a higher yield upon isolation and a greater proliferative rate in culture when compared to BMSCs [18
]. The discovery that ADSCs are not only precursor to adipocytes, but are multipotent progenitors to a variety of cells [21
] was a milestone that has allowed scientists to utilize the true potential of ADSCs to derive several additional cell types including osteoblasts, chondrocytes, myocytes, epithelial cells and neuronal cells [22
]. For the plastic surgeon, they are an abundant source of multipotent stem cells that can be easily accessed during many routine procedures.
Stem cells are a promising therapeutic modality for the treatment of tissue defects, malformations and disease, and an attractive tool for the enhancement of aesthetic medicine. However, scientific evidence on clinical applications is still limited and much is unknown about the safety and efficacy of stem cell therapies [23
]. Several key issues must be considered including the 1) source of stem cells, 2) efficiency of transplantation, 3) engraftment in host tissue, 4) interaction with the surrounding microenvironment, and 5) long term fate of transplanted cells. By further elucidating the current strategies for stem cell utilization, this review aims to provide a better understanding of the current state of cellular regenerative techniques in plastic surgery, the progress that remains to be made, and the appropriate direction for future research.