Research has shown the importance of follistatin, Wnt 7a, and wound healing growth factors on the stimulation of bulge cells and inter-follicular stem cells to induce hair growth. We have studied the effects of a bioengineered, non-recombinant, human cell-derived formulation, termed Hair Stimulating Complex (HSC), containing these factors to assess its hair growth activity in male pattern baldness. HSC showed in vitro Wnt activity and contained follistatin, KGF, and VEGF. The clinical study was a double-blind, placebo-controlled, randomized single site trial and was designed to evaluate safety of the HSC product and assess efficacy in stimulating hair growth. All 26 subjects tolerated the single, intradermal injection of HSC procedures well, and no signs of an adverse reaction were reported. Histopathological evaluation of the treatment site biopsies taken at 22 and 52 weeks post-treatment revealed no abnormal morphology, hamartomas, or other pathological responses. Trichoscan image analysis of HSC-treated sites at 12 and 52 weeks showed significant improvements in hair growth over the placebo. At the initial 12-week evaluation period, HSC-treated sites demonstrated an increase in hair shaft thickness (6.3%±2.5% vs. -0.63%±2.1%; P=0.046), thickness density (12.8%±4.5% vs. -0.2%±2.9%; P=0.028), and terminal hair density (20.6±4.9% vs. 4.4±4.9%; P=0.029). At one year, a statistically significant increase in total hair count (P=0.032) continued to be seen. These results demonstrate that a single intradermal administration of HSC improved hair growth in subjects with androgenetic alopecia and is a clinical substantiation of previous preclinical research with Wnts, follistatin, and other growth factors associated with wound healing and regeneration.

INTRODUCTION

Androgenetic alopecia is a widespread cosmetic and medical disorder for which there exist few treatment options. The current therapeutic strategies including surgical, pharmaceutical, and cosmetic interventions are limited in approach and success. We have developed a bioengineered human cell-derived formulation, termed Hair Stimulating Complex (HSC) that consists of a number of human growth factors and morphogens recognized to be critical to the induction and maintenance of hair follicle growth and activity. Here we report that the preparation is safe as applied and showed effectiveness in stimulating hair growth following the clinical administration of HSC to men with male-pattern baldness in a first-in-human, phase 1 clinical study.

In the HSC manufacturing process, neonatal dermal fibroblasts, which are closely related to hair follicle dermal papilla cells, are seeded onto microcarrier beads and grown in suspension culture under hypoxic conditions that simulate the embryonic environment. Under these conditions, the cells differentially express over 5,000 genes compared to cells grown in normoxic environments. Several of the upregulated genes expressed in the hypoxic cells are associated with pluripotent and follicular stem cells including LnX2, SOX21, Nestin, NFATc1, Krt15, POU5F1 (OCT4), SOX2 and Nanog. In addition, WNT7a, VEGF, FGF, KGF and follistatin are upregulated in these cells. In the adult, Wnt proteins have been found to play an essential role in induction of the dermal papilla1,2 and triggering of stem cell activity in keratinocytes3 to produce new hair follicles and growth. Follistatin is an antagonist of activin and BMP, which are involved in maintaining a slow cycling stem cell phenotype in resting hair follicles.4 The exogenous administration of Wnt proteins and follistatin to the scalp represents a novel and practical way to ameliorate and reverse androgenetic alopecia and other related hair loss disorders. The presence of Wnt proteins