Great interest remains in finding new and emerging therapies for the treatment of male and female pattern hair loss. The autologous fat grafting technique is >100 years old, with a recent and dramatic increase in clinical experience over the past 10–15 years. Recently, in 2001, Zuk et al published the presence of adipose-derived stem cells, and abundant research has shown that adipose is a complex, biological active, and important tissue. Festa et al, in 2011, reported that adipocyte lineage cells support the stem cell niche and help drive the complex hair growth cycle. Adipose-derived regenerative cells (also known as stromal vascular fraction [SVF]) is a heterogeneous group of noncultured cells that can be reliably extracted from adipose by using automated systems, and these cells work largely by paracrine mechanisms to support adipocyte viability. While, today, autologous fat is transplanted primarily for esthetic and reconstructive volume, surgeons have previously reported positive skin and hair changes posttransplantation. This follicular regenerative approach is intriguing and raises the possibility that one can drive or restore the hair cycle in male and female pattern baldness by stimulating the niche with autologous fat enriched with SVF. In this first of a kind patient series, the authors report on the safety, tolerability, and quantitative, as well as photographic changes, in a group of patients with early genetic alopecia treated with subcutaneous scalp injection of enriched adipose tissue. The findings suggest that scalp stem cell-enriched fat grafting may represent a promising alternative approach to treating baldness in men and women.
Male and female pattern of hair loss (MPHL and FPHL) is characterized by progressive thinning of the scalp hair. MPHL affects half or more of males before the age of 50 years.1–6 In women, FPHL is a common condition characterized by diffuse thinning and reduction of hair density in the frontal and mid-scalp and crown with retention of the hairline. Prevalence of FPHL increases with age, and ~50% of women experience FPHL by age 50.7–9 Great interest remains in finding new and emerging therapies for the treatment of MPHL and FPHL. Treatment options for men and women with hair loss include medical therapy, hair transplant surgery, low-level laser therapy, hair systems, micropigmentation of the scalp, and topical concealer fibers.10–17 These options are not without shortcomings, and thus researchers are always looking for new and alternative therapies.18–23 One emerging area of clinical and scientific focus lies in exploring the role of adipose tissue (fat), and specifically autologous adipose transplantation, in the complex, hair growth cycle. While modern efforts to seek a treatment for pattern baldness have been ongoing for decades, autologous fat grafting is a technique practiced for over a century. The procedure has enjoyed a recent and dramatic increase in clinical experience over the past 10–15 years, and this resurgence in clinical activity has been, in part, driven by the findings of Zuk et al, reporting the presence of adipose-derived stem cells (ADSCs).24 Subsequently, abundant research has supported the fact that adipose is a biologically active, a complex, and an important tissue. In the context of the scalp, Festa et al reported that adipocyte lineage cells support the stem cell niche and help drive the hair growth cycle, while Shin et al documented the role of ADSC-conditioned media in promoting hair growth in female pattern alopecia.25,26 Today, autologous fat is transplanted primarily for an esthetic and reconstructive volume effect and, traditionally, rates of graft retention have been widely varied and a number of strategies have been applied to increase this rate of graft take.27 One such strategy is to enrich the adipose with stromal vascular fraction (SVF), a heterogeneous group of generally well-characterized multinucleated cells that can be reliably extracted from adipose by using automated systems. These cells work largely by paracrine mechanisms to support adipocyte viability.27 Beyond volumization, many surgeons have reported positive skin and hair changes posttransplantation.28,29 This background spurred these authors to ask if one could drive or restore the hair cycle by transplanting adipose enriched with SVF to the scalp in patients with MPHL and FPHL. In this pilot case series, the authors’ first experience and findings are reported.
Adipose cells organized in small clusters under the reticular dermis closely interact with hair follicular cells and regulate the hair cycle. Intradermal adipocyte progenitor cells are activated toward the end of the telogen phase to proliferate and differentiate into mature adipocytes. These cells, surrounding the hair follicles, secrete signaling molecules that control the progression of the hair cycle. Diseases associated with defects in adipocyte homeostasis, such as lipodystrophy and focal dermal hypoplasia, lead to alopecia. In this review, we discuss the potential influence of stromal vascular fraction from adipose tissue in the management of alopecia as well as its involvement in preclinical and clinical trials.
Adipose tissue is a loose connective tissue composed of cells supported by an intracellular matrix as well as by vascular, lymphatic, and neural networks.1 The major cellular component of fat tissue is the adipocyte; however, a variety of other cell types are found as well, collectively labeled as stromal vascular fraction (SVF).2 SVF was first isolated by Zuk et al3 in 2001 from lipoaspirate obtained by liposuction. Specifically, SVF contains mature cells (e.g., fibroblasts, smooth muscle, endothelial, blood cells), progenitor cells (e.g., preadipocytes and endothelial, vascular, and hematopoietic progenitors), and, most importantly, stem cells (e.g., mesenchymal and hematopoietic stem cells, pericytes, and supra-adventitial cells), which are also known as adipose tissue-derived stromal cells (ASCs).4, 5
It has been found that some of the SVF cell types possess regenerative and anti-inflammatory potentials in damaged tissues due to their ability to secrete growth factors and anti-inflammatory molecules.6,7 Mesenchymal stem cells (MSCs) have also been isolated from other sources, such as bone marrow,8 the placenta,9 muscle,10 or blood.11 However, the greater the abundance of adipose tissue in the human body, the significantly higher the yield of MSCs is compared to other tissues.12 Furthermore, the simplicity of harvesting has made fat one of the most important sources for such cells.
As a result, SVF has attracted substantial attention for its potential use in regenerative medicine in various fields, including internal medicine,13–15 orthopedics,16 plastic and general surgery,17–19 and wound healing.7 More recently, the potential role of SVF in hair growth has been investigated for its anticipated contribution to alopecia management. Scalp hair is a key element in the appearance of the individual in addition to the thermoregulation and protection of the skin. Cases of alopecia can be classified by the distribution of hair loss as either diffuse, patterned, or patchy and by the absence or presence of scarring. A thorough description of the etiopathogenesis, diagnosis, and treatment options is presented elsewhere.20,21
Androgenic alopecia is the most common form of alopecia, affecting an estimated 80 percent of men and 50 percent of women by the age of 70 years.22,23 It is classified as a nonscarring patterned form of alopecia and is characterized by bitemporal recession, a gradual loss of hair in the frontoparietal region in men, and a diffuse hair thinning with preservation of frontal hairline in women.22 The underlying mechanism is believed to be a higher concentration of dihydrotestosterone (DHT) to androgen-sensitive hair follicles, causing thinning of the dermal papillae and shortening of the anagen phase.24,25 Current well-established treatment modalities focus on reducing the androgenic effects on hair follicles (5a-reductase inhibitors), stimulating hair growth (minoxidil), or transferring androgen-independent hair to the affected scalp (hair transplantation).23
Diseases associated with defects in adipocyte production, such as in lipodystrophy and focal dermal hypoplasia, leads to alopecia.26,27 Dermal adipocytes are organized in small clusters under the reticular dermis and interact with the hair follicular cells regulating the hair cycle.28 Intradermal adipocyte progenitor cells are stimulated at the end of the telogen phase, multiplying and differentiating into mature adipocytes, which then surround the hair follicles and secrete signaling molecules, such as platelet-derived growth factor (PDGF), leptin, adiponectin, and bone morphogenetic protein 2.29 The expression of these molecules induces the anagen phase of the hair cycle and promotes hair growth.29
The purpose of this review is to provide a synopsis of different SVF isolation methods and the involved components and to provide a description of possible mechanisms for SVF contribution to tissue remodeling and regeneration. It also presents a critical outline of the research concerning the application of SVF and its constituents in the treatment of hair loss where the applied SVF is expected to support the dermal adipose tissue.