The Anti-Aging Effects of Low Oxygen Tension Generated Multipotent Growth Factor Containing Serum

January 2017 | Volume 16 | Issue 1 | Original Article | 30 | Copyright © January 2017

Zoe Diana Draelos MD,a Jwala Karnik MD,b and Gail Naughton PhDc

aDermatology Consulting Services, High Point, NC bSuneva Medical Inc., San Diego, CA cHistogen Inc., San Diego, CA

Growth factors are a new category of ingredient found in modern cosmeceutical formulations. One novel method of obtaining cosmeceutical growth factors is the use of a bioreactor to culture neonatal broblasts on dextran microcarrier beads for 8 weeks under low oxygen tension (1-5%) mimicking embryonic conditions and eliminating the need for fetal bovine serum constituents in the final cosmetic material. This research evaluated the ingredient in a moisturizing vehicle on 40 females to determine its efficacy in improving overall facial skin appearance, as well as skin brightness, evenness, firmness, pore size, radiance, fine lines, coarse wrinkles, and blotchiness/ dispigmentation. Statistically significant improvement was seen in 90 days in skin hydration through corneometry, as well in global investigator and subject assessments. J Drugs Dermatol. 2017;16(1):30-34.


Skin appearance deteriorates with advancing age due to the cumulative insults of life in an oxygen rich environment. Oxygen radicals that are generated by UV exposure, environmental free radicals, and the processes of metabolism result in the production of reactive oxygen species that are damaging to human tissues, including the skin.1 While reactive oxygen species produce injury to all body structures, these insults are most apparent in the skin.2 These insults induce changes in the skin associated with aging that can be classified as a reduction in skin brightness, evenness, firmness, and radiance. Reductions in elasticity, increased blotchiness, and abundant fine lines are also part of this degradative process. Cosmeceutical moisturizers aim to improve skin appearance by protecting against oxygen radical induced negative attributes. One new area of research involves the manufacture and use of multipotent growth factors with subsequent formulation into facial moisturizers.3 A number of growth factor products are currently in the marketplace. These include formulations containing a mixture of growth factors and cytokines obtained from the lysate of cultured human fibroblasts.4 Another technology utilizes conditioned media from neonatal fibroblast culture.5 A third technology, the subject of this research, involves the use of multipotent growth factors derived from neonatal fibroblasts cultured in a bioreactor on dextran microcarrier beads under low oxygen conditions (1-5 %) mimicking embryonic conditions. The cells are cultured for 8 weeks without the need for fetal bovine serum constituents in the final product.The hypoxic conditioned culture medium (HCCM) is then concentrated using a 10 kDa lter and tested for sterility, as well as the following constituents: endotoxin, follistatin, and keratinocyte growth factor (KGF).6 An analysis of the HCCM material as compared to standard cell conditioned media cultured under normoxic conditions revealed that the hypoxic culture environment resulted in a 11.51 fold increase in KGF and a 4.33 fold increase in VEGFB.7 A different formulation of the multipotent growth factor has been investigated as an injectable treatment for hair regrowth and has shown safety and efficacy for a period of two years after treatment.8 A proof of concept study for facial aging was also conducted.9 The objective of this study was to determine the efficacy of a novel anti-aging serum in improving overall facial skin appearance as well as skin brightness, evenness, firmness, pore size, radiance, fine lines, coarse wrinkles, and blotchiness/ dispigmentation.


Forty female subjects with mild to severe photodamage, 18-59 years of age with Fitzpatrick skin types I-IV were enrolled in this 90-day single investigator site, open-label study. Mild to severe photoaging was defined as an overall score of 2-4 on photoaging scale (0=none, 1=minimal, 2=mild, 3=moderate, 4=severe) evaluating lines, wrinkles, uneven skin texture, enlarged pores, and lack of firmness. Subjects completed an informed consent, underwent a past medical history and concomitant medication evaluation, and met all of the inclusion criteria and none of the exclusion criteria. Subjects were not allowed to undergo any cosmetic facial procedures 6 months before or during the