Regenerative Medicine in Cosmetic Dermatology

Regenerative medicine encompasses innovative therapies that allow the body to repair or regenerate aging cells, tissues, and organs. The skin is a particularly attractive organ for the application of novel regenerative therapies due to its easy accessibility. Among these therapies, stem cells and platelet-rich plasma (PRP) have garnered interest based on their therapeutic potential in scar reduction, antiaging effects, and treatment of alopecia.

Stem cells possess the cardinal features of self-renewal and plasticity. Self-renewal refers to symmetric cell division generating daughter cells identical to the parent cell.¹ Plasticity is the ability to generate cell types other than the germ line or tissue lineage from which stem cells derive.² Stem cells can be categorized according to their differentiation potential. Totipotent stem cells may develop into any primary germ cell layer (ectoderm, mesoderm, endoderm) of the embryo, as well as extraembryonic tissue such as the trophoblast, which gives rise to the placenta. Pluripotent stem cells such as embryonic stem cells have the capacity to differentiate into any derivative of the 3 germ cell layers but have lost their ability to differentiate into the trophoblast.³ Adults lack totipotent or pluripotent cells; they have multipotent or unipotent cells. Multipotent stem cells are able to differentiate into multiple cell types from similar lineages; mesenchymal stem cells (MSCs), for example, can differentiate into adipogenic, osteogenic, chondrogenic, and myogenic cells.⁴ Unipotent stem cells have the lowest differentiation potential and can only self-regenerate. Herein, we review stem cell sources and their therapeutic potential in aesthetic dermatology.

Multipotent Stem Cells

Multipotent stem cells derived from the bone marrow, umbilical cord, adipose tissue, dermis, or hair follicle bulge have various clinical applications in dermatology. Stem cells from these sources are primarily utilized in an autologous manner in which they are processed outside the body and reintroduced into the donor. Autologous multipotent hematopoietic bone marrow cells were first successfully used for the treatment of chronic wounds and show promise for the treatment of atrophic scars.^5,6 However, due to the invasive nature of extracting bone marrow stem cells and their declining number with age, other sources of multipotent stem cells have fallen into favor.

Umbilical cord blood is a source of multipotent hematopoietic stem cells for which surgical intervention is not necessary because they are retrieved after umbilical cord clamping.⁷ Advantages of sourcing stem cells from umbilical cord blood includes high regenerative power compared to a newborn’s skin and low immunogenicity given that the newborn is immunologically immature.⁸

Another popular source for autologous stem cells is adipose tissue due to its ease of accessibility and relative abundance. Given that adipose tissue–derived stem cells (ASCs) are capable of differentiating into adipocytes that help maintain volume over time, they are being used for midface contouring, lip augmentation, facial rejuvenation, facial scarring, lipodystrophy, penile girth enhancement, and vaginal augmentation. Adipose tissue–derived stem cells also are capable of differentiating into other types of tissue, including cartilage and bone. Thus, they have been successfully harnessed in the treatment of patients affected by systemic sclerosis and Parry-Romberg syndrome as well in the functional and aesthetic reconstruction of various military combat–related deformities.^9,10

Adipose tissue–derived stem cells are commonly harvested from lipoaspirate of the abdomen and are combined with supportive mechanical scaffolds such as hydrogels. Lipoaspirate itself can serve as a scaffold for ASCs. Accordingly, ASCs also are being utilized as a scaffold for autologous fat transfer procedures in an effort to increase the viability of transplanted donor tissue, a process known as cell-assisted lipotransfer (CAL). In CAL, a fraction of the aspirated fat is processed for isolation of ASCs, which are then recombined with the remainder of the aspirated fat prior to grafting.¹¹ However, there is conflicting evidence as to whether CAL leads to improved graft success relative to conventional autologous fat transfer.^12,13

The skin also serves as an easily accessible and abundant autologous source of stem cells. A subtype of dermal fibroblasts has been proven to have multipotent potential.^14,15 These dermal fibroblasts are harvested from one area of the skin using punch biopsy and are processed and reinjected into another desired area of the skin.¹⁶ Autologous human fibroblasts have proven to be effective for the treatment of wrinkles, rhytides, and acne scars.¹⁷ In June 2011, the US Food and Drug Administration approved azficel-T, an autologous cellular product created by harvesting fibroblasts from a patient’s own postauricular skin, culture-expanding them in vitro for 3 months, and reinjecting the cells into the desired area of dermis in a series of treatments. This product was the first personalized cell therapy approved by the US Food and Drug Administration for aesthetic uses, specifically for the improvement of nasolabial fold wrinkles.¹⁸

In adults, hair follicles contain an area known as the bulge, which is a site rich in epithelial and melanocytic stem cells. Bulge stem cells have the ability to reproduce the interfollicular epidermis, hair follicle structures, and sebaceous glands, and they have been used to construct entirely new hair follicles in an artificial in vivo system.¹⁹ Sugiyama-Nakagiri et al²⁰ demonstrated that an entire hair follicle epithelium and interfollicular epidermis can be regenerated using cultured bulge stem cells. The cultured bulge stem cells were mixed with dermal papilla cells from neonatal rat vibrissae and engrafted into a silicone chamber implanted on the backs of severe combined immune deficient (SCID) mice. The grafts exhibited tufts of hair as well as a complete interfollicular epidermis at 4 weeks after transplantation.²⁰ Thus, these bulge stem cells have the potential to treat male androgenic alopecia and female pattern hair loss. Bulge stem cells also have been shown to accelerate wound healing.²¹ Additionally, autologous melanocytic stem cells located at the hair follicle bulge are effective for treating vitiligo and are being investigated for the treatment of hair graying.²²