Efficacy of Microneedling combined with Human Umbilical cord Derived

Efficacy of Microneedling combined with Human Umbilical cord Derived

Efficacy of Microneedling Combined With Local Application of Human Umbilical Cord-Derived Mesenchymal Stem Cells Conditioned Media in Skin Brightness and Rejuvenation: A Randomized Controlled Split-Face Study

📷Xuelei Liang1†📷Jiaying Li2†📷Yan Yan1📷Yongsheng Xu1📷Xiujuan Wang1📷Haixuan Wu1📷Yi Liu1📷Linfeng Li1📷Fenglin Zhuo1*

1. Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China

2. Department of Dermatology, Xuanwu Hospital, Capital Medical University, Beijing, China

Background: Fighting skin aging signs is one of the major challenges of the 21st century, recently, mesenchymal stem cells (MSCs) and microneedling (MN) have been applied for anti-aging. This study aims to evaluate the efficacy of the combination of MN and human umbilical cord-derived mesenchymal stem cells conditioned media (hUC-MSCs-CM) in skin brightness and rejuvenation.

Methods: Thirty volunteers with facial skin aging were recruited for the randomized, controlled split-face study. The left and right sides of the face were randomly applied with saline via MN or hUC-MSCs-CM via MN. Five sessions were performed for each volunteer at 2-week intervals. Two dermatologists evaluated the clinical improvement, in terms of skin brightness and texture. A satisfaction score based on a self-evaluation questionnaire was recorded at 2 weeks after the last treatment. The objective evaluation was recorded before the first treatment, and at 2 weeks after the last treatment.

Results: Twenty-eight volunteers with a mean (SD) age of 41 (6.54) years old completed the trial. The investigator’s assessment for skin brightness and texture, and the self-satisfaction score revealed statistically better effects in hUC-MSCs-CM -plus-MN group than in MN alone (MN saline) group. No severe side effects were reported during the whole study period. Compared to MN alone group, the objective assessment revealed significant improvements in skin brightness (reduced melanin index, ultraviolet spots, and brown spots) and skin texture (reduced wrinkles and pores, and increased skin elasticity) in hUC-MSCs-CM-plus-MN group, while there were no obvious differences in skin hydration, trans-epidermal water loss, and the erythema index.

Conclusion: The combination of hUC-MSCs-CM and MN exhibite anti-aging efficacy, and this could be used for facial rejuvenation in the future.

Introduction

Skin aging is subject to both intrinsic (chronological) and extrinsic (environmental) factors, resulting in poor appearance and loss of functional capacity. Rejuvenating skin by fighting aging signs, such as wrinkles, enlarged pores, reduced resilience and irregular pigmentation, is one of the major challenges of the 21st century (1). Skin aging not only affects physiological skin function, but also has impacts on a person’s psychology and social life. As a result, several non-surgical treatments, such as oral treatments, ointments, dermabrasion, chemical peels, and laser therapy, have been developed over the past years, in order to counteract skin aging. However, these may be associated with prolonged recovery, dyspigmentation, and scarring.

Mesenchymal stem cells (MSCs) have the advantage of being easy to isolation, expansion, and multipotentiality, so they are popular in the field of skin rejuvenation therapy (2). These release several growth factors in autocrine and paracrine ways (3). There are various types of MSCs, including adipose-derived stem cells, bone marrow-derived stem cells (BMMSCs), and umbilical cord-derived mesenchymal stem cells. A recent study indicated that compared to BMMSCs-conditioned media, UC-MSCs-conditioned media (UC-MSCs-CM) can form premature adipocytes, collagen type 1 and collagen type 2 which have anti-aging effects (4).

Microneedling (MN) is a treatment widely applied for skin diseases and skin rejuvenation, due to its safety and efficacy. There are two main reasons for its medical use: (i) MN can accelerate the process of the skin’s natural healing. It penetrates the epidermis and papillary dermis (5), creating pores, and thereby triggering the skin’s repair mechanism (6). This can result in the short-term aggregation of inflammatory cells, fibroblasts proliferation, long-term remodeling, and the synthesis of collagen and elastin (5). (ii) MN can enhance the penetration of drugs (5). It is difficult for drugs to be absorbed through the skin due to the stratum corneum barrier (7). MN creates small transient holes that penetrate the stratum corneum barrier within a short period of time (8).

The present study aims to explore the synergistic effect of MN combined with hUC-MSCs-CM against aging skin. Non-invasive skin-measuring devices were used to objectively assess the changes in skin brightness and rejuvenation before and at 2 weeks after the final treatment.

Materials and Methods

Subjects

A total of 30 volunteers with facial photo-aging (Fitzpatrick III 20, IV 10) were included for the present study. Two participants were withdrawn from the study due to job-related factors. The remaining 28 volunteers completed the study. These volunteers were within 35–60 years old, with a mean (SD) age of 41 (6.54) years old. The exclusion criteria included obvious inflammation, ulcer or effusion on the face, and previous skin rejuvenation treatment in the past 3 months.

Study Design

The present study was a randomized controlled split-face study. The Institutional Review Board of Beijing Friendship Hospital, Capital Medical University approved the study (Approval No. 2017-P2-086-01). All volunteers were thoroughly counseled on the potential risks and benefits before they signed the informed consent form, based on the 1975 Declaration of Helsinki. The registration number in http://www.chictr.org.cn is ChiCTR-INR-17013311.

Randomization and Allocation Concealment

MN plus hUC-MSCs-CM (Beijing Origife Health Care Co., Ltd., China) group and MN alone group (control) were randomly allocated to the left or right face side. Each participant was assigned a number, according to the random number table created by the computer software. If the number was odd, the left side was used as the test side. If the number was even, the right side was used as the test side. To ensure allocation concealment, the doctors in MN operation wore colorful glasses which are normally used to protect the eyes from Intense pulse Light treatment in our department. While each volunteer’s eyes were covered with eight layers of sterile gauze before treatment.

Intervention

Prior to treatment, the faces of all participants were cleaned using facial cleanser (Nivea, Nivea Co., Ltd., Shanghai, China) and anesthetized with 5% compound lidocaine cream (Beijing Unisplendour Pharmaceutical Co., Ltd., China). For one side, 1.0 ml of saline or hUC-MSCs-CM was painted and the remaining 1.0 ml was added locally after dermaroller MN treatment, which was performed in eight rows, with a total of 192 needles, 0.5 mm in length (Suzhou Cynour Photoelectric Technology Co., Ltd., China)., the same method was performed on the other side. The endpoint of treatment was the presence of uniform erythema over the face. Generally, 2 ml saline or hUC-MSCs-CM could be completely absorbed. The participants received five sessions of treatment at 2-week intervals for a total of 10 weeks. Table 1 presents the densities of the main growth factors derived from hUC-MSCs-CM, which were measured using the Human ProcartaPlex Growth Factor Panel (11 plex) (Cat. No. EPX110-12170-901, Invitrogen, Thermo Fisher, United States).