Improvement in Skin Elasticity Using Red Deer Umbilical Cord Lining Mesenchymal Stem Cell Conditioned Media

January 2023 | Volume 22 | Issue 1 | 82 | Copyright © January 2023


Published online December 28, 2022

Chee Tian Ong BSCa, Ivor Jiun Lim MDa, Mitchel P. Goldman MDb, Nina Hartman MDb, Jeyakumar Masilamani PhDa, Toan Thang Phan MD PhDa

aCellResearch Corporation, Singapore
bCosmetic Laser Dermatology: A West Dermatology Company, San Diego, CA

Abstract
Background: Significant improvement in skin tone was reported after topical application of a facial cream (CALECIM® Professional Multi-Action Cream, CALECIM Cosmeceuticals, Singapore) containing conditioned media (CM) derived from Red Deer Umbilical Cord Lining Mesenchymal Stem Cell (RD-CLMSC) culture. This study investigates the paracrine effects of RD-CLMSC-CM on human dermal fibroblasts (HDF) to understand how it may increase skin turgor and elasticity.

Skin aging is associated with lower levels of extracellular matrix components such as hyaluronic acid (HA) and elastin, resulting in poor skin turgor and elasticity. Histochemical staining followed by photocolorimetry demonstrated that RD-CLMSC-CM upregulated HDF expression of elastin by 56% and HA by 83% compared with DMEM/10% Fetal Calf Serum (FCS).

To further quantify the effects of CM, a proliferation assay was used to assess HDF response to RD-CLMSC-CM exposure. Exposure to RD-CLMSC-CM resulted in the highest increase in HDF proliferation over DMEM/10% FCS (113%) followed by Human (H)-CLMSC-CM (112%), then Human Foreskin Fibroblast (FSF)-CM (16%).

These experimental results demonstrate both the cross-species efficacy and lack of toxicity of RD-CLMSC-CM on HDF. These pre-clinical studies also suggest the clinical effects of RD-CLMSC-CM on skin turgor may be related to increased HA and elastin production by HDF, as well as enhanced proliferation.

J Drugs Dermatol. 2023;21(1):82-89. doi:10.36849/JDD.6906

Citation: Ong C, Lim I, Goldman M, et al. Improvement in skin elasticity using red deer umbilical cord lining mesenchymal stem cell conditioned media. J Drugs Dermatol. 2023 Jan 1;22(1):82-89. doi: 10.36849/JDD.6906.

INTRODUCTION

Stem cells were first isolated from the bone marrow.1 Since that time, they have also been found in adipose tissue, dental pulp, various parts of the placenta and umbilical cord, and embryos.2 The placenta and umbilical cord, which are often discarded after delivery, represent attractive stem cell sources given their ethical acceptability.

In 2004, Cord Lining Mesenchymal Stem Cells (CLMSC) and Cord Lining Epithelial Stem Cells (CLEpSC) were isolated from the umbilical cord and found to be present in enormous quantities with extremely high purity.3 The cells were additionally found to express non-classical HLA subtypes, HLA-E and HLA-G, which conferred immune protection to these cells by suppressing rejection. Human Cord Lining Mesenchymal Stem Cells (H-CLMSC) seeded on a Biobrane (Smith and Nephew, Hull, UK) scaffold were used initially as a biological dressing to improve granulation tissue in burn patients prior to skin grafting. Accelerated wound re-epithelialisation and healing was observed. This led to the application of H-CLMSC to other chronic wounds which demonstrated accelerated wound healing (unpublished observations). Current Good Manufacturing Practice (cGMP) grade H-CLMSC cultured and expanded in a Biologics Licensing Application (BLA) facility at the University of Colorado Anschutz Medical Campus are currently being used in a United States Food and Drug Administration (USFDA) trial to accelerate wound healing in chronic diabetic foot ulcers.7 Given the positive effects of H-CLMSC on wound healing, it was postulated that they may also be beneficial in the rejuvenation of aged skin. Guided by the Association of South East Asian Nations (ASEAN) Cosmetic Directive, which prohibits cosmetic products containing derivatives of human origin, umbilical cords from Red Deer (RD) raised for horn velvet in New Zealand