Autologous Cell Therapy for Aged Human Skin: A Randomized, Placebo-Controlled, Phase-I Study

Abstract

Introduction: Skin ageing involves senescent fibroblast accumulation, disturbance in extracellular matrix (ECM) homeostasis, and decreased collagen synthesis. Objective: to assess a cell therapy product for aged skin (RCS-01) consisting of ~25 x 10 6 cultured, autologous cells derived from anagen hair follicle non-bulbar dermal sheath (NBDS). Methods: For each subject in the verum group, four areas of buttock skin were injected intradermally 1 or 3 times at monthly intervals with RCS-01, cryomedium, or needle penetration without injection; in the placebo group RCS-01 was replaced by cryomedium. The primary endpoint was assessment of local adverse event profiles. As secondary endpoints, expression of genes related to ECM homeostasis was assessed in biopsies from randomly selected volunteers in the RCS-01 group taken 4 weeks after the last injection. Results: Injections were well tolerated with no severe adverse events reported 1 year after first injection. When compared with placebo treated skin, a single treatment with RCS-01 resulted in a significant upregulation of TGFß1, CTGF, COL1A1, COL1A2, COL3A1, and lumican mRNA expression. Limitations: The cohort size was insufficient for dose ranging evaluation and subgroup analyses of efficacy. Conclusions: RCS-01 therapy is well tolerated and associated with a gene expression response consistent with an improvement of ECM homeostasis.

Environmentally-Induced (Extrinsic) Skin Aging: Exposomal Factors and Underlying Mechanisms

“…In addition, a more detailed assessment of the mechanisms involved in the dermal accumulation of macromolecular damage by exposomal factors beyond UVR is needed. Targeting the resulting functional consequences, for example, by deleting damaged and/or senescent fibroblasts by means of senolytics (Xu et al, 2018;Zhu et al, 2015), by improving their capacity to adapt, or by overriding their malfunctions through cell-based interventions (Grether-Beck et al, 2020), might prove effective to partially revert extrinsic skin aging.…”

Alpha-Tocopherol Protects Human Dermal Fibroblasts by Modulating Nitric Oxide Release, Mitochondrial Function, Redox Status, and Inflammation

“…Even more relevant is the involvement of the senescent fibroblasts not only in the early stages of skin carcinogenesis [32] but also in cancer cell migration and metastasis, both in melanoma [33] and in NMSC [34]. Therefore, the preservation of their functionality can be a strategy in the prevention of intrinsic and extrinsic skin aging and even cutaneous carcinogenesis [35,36].…”

Eternal Youth: A Comprehensive Exploration of Gene, Cellular, and Pharmacological Anti-Aging Strategies

“…RCS-01 injections were well tolerated, with no reported serious side effects. A single injection of RCS-01 led to a significant increase in the mRNA expression of TGF-β1 , connective tissue growth factor ( CTGF ), type I collagen ( COL1 ) A1 , COL1A2 , COL3A1 , and lumican genes (NCT02391935) [ 104 ].…”