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

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; verum) consisting of ~25 × 106 cultured, autologous cells derived from anagen hair follicle non-bulbar dermal sheath (NBDS). METHODS: For each subject in the verum group, 4 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 the 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.

Experimental and early investigational drugs for androgenetic alopecia.

INTRODUCTION: Treatments for androgenetic alopecia constitute a multi-billion-dollar industry, however, currently available therapeutic options have variable efficacy. Consequently, in recent years small biotechnology companies and academic research laboratories have begun to investigate new or improved treatment methods. Research and development approaches include improved formulations and modes of application for current drugs, new drug development, development of cell-based treatments, and medical devices for modulation of hair growth. Areas covered: Here we review the essential pathways of androgenetic alopecia pathogenesis and collate the current and emerging therapeutic strategies using journal publications databases and clinical trials databases to gather information about active research on new treatments. Expert opinion: We propose that topically applied medications, or intra-dermal injected or implanted materials, are preferable treatment modalities, minimizing side effect risks as compared to systemically applied treatments. Evidence in support of new treatments is limited. However, we suggest therapeutics which reverse the androgen-driven inhibition of hair follicle signaling pathways, such as prostaglandin analogs and antagonists, platelet-rich plasma (PRP), promotion of skin angiogenesis and perfusion, introduction of progenitor cells for hair regeneration, and more effective ways of transplanting hair, are the likely near future direction of androgenetic alopecia treatment development.

CXCR3/ligands are significantly involved in the tumorigenesis of basal cell carcinomas.

Basal cell carcinoma (BCC) is the most common skin malignancy encountered worldwide. We hypothesized that CXC chemokines, small cytokines involved in inducing directed leukocyte chemotaxis, could play a key role in the modulation of BCC growth. In this study, quantitative RT-PCR revealed that the chemokines CXCL9, 10, 11, and their receptor CXCR3 were significantly upregulated by an average 22.6-fold, 9.2-fold, 26.6-fold, and 4.9-fold, respectively in BCC tissue samples as compared with nonlesional skin epithelium. Immunohistochemistry analysis revealed that CXCR3, CXCL10, and CXCL11, but not CXCL9, colocalized with cytokeratin 17 (K17) in BCC keratinocytes. In addition, CXCR3 and its ligands were expressed in cells of the surrounding BCC stroma. The chemokines and K17 were also expressed in cultured human immortalized HaCaT keratinocytes. Exposure of HaCaT cells or primary BCC-derived cells to CXCL11 peptides in vitro significantly increased cell proliferation. In primary BCC-derived cell cultures, addition of CXCL11 progressively selected for K17+/CXCR3+ co-expressing cells over time. The expression of CXCR3 and its ligands in human BCC keratinocytes, the enhancement of keratinocyte cell proliferation by CXCL11, and the homogeneity of K17+ BCC cells in human BCC-isolated cell population supported by CXCR3/CXCL11 signaling all suggest that CXCR3 and its ligands may be important autocrine and/or paracrine signaling mediators in the tumorigenesis of BCC.

Diagnosis and management of primary cicatricial alopecia: part II.

The second part of this 2-part article reviews clinical features, histology, management, and treatment of neutrophilic primary cicatricial alopecias (folliculitis decalvans and dissecting folliculitis) and mixed primary cicatricial alopecias (acne keloidalis, acne necrotica, and erosive pustular dermatosis).

Diagnosis and management of primary cicatricial alopecia: part I.

In this 2-part article, the authors review the primary cicatricial alopecias. Primary cicatricial alopecia can be defined as predominantly lymphocytic, neutrophilic, or mixed based on the nature of the follicular infiltrate that is present around affected hair follicles. Lymphocytic primary cicatricial alopecias include chronic cutaneous lupus erythematosus (discoid lupus erythematosus), lichen planopilaris, classic pseudopelade of Brocq, central centrifugal cicatricial alopecia, alopecia mucinosa, and keratosis follicularis spinulosa decalvans. In this first part, the authors summarize the classification, epidemiology, diagnostic approach, and patient management of lymphocytic cicatricial alopecias. In part II, the authors will focus on neutrophilic cicatricial alopecias and mixed cicatricial alopecias.