Frontiers in Lichen Planopilaris and Frontal Fibrosing Alopecia Research: Pathobiology Progress and Translational Horizons.

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are primary, lymphocytic cicatricial hair loss disorders. These model epithelial stem cell (SC) diseases are thought to result from a CD8+ T-cell‒dominated immune attack on the hair follicle (HF) SC niche (bulge) after the latter has lost its immune privilege (IP) for as yet unknown reasons. This induces both apoptosis and pathological epithelial‒mesenchymal transition in epithelial SCs, thus depletes the bulge, causes fibrosis, and ultimately abrogates the HFs' capacity to regenerate. In this paper, we synthesize recent progress in LPP and FFA pathobiology research, integrate our limited current understanding of the roles that genetic, hormonal, environmental, and other factors may play, and define major open questions. We propose that LPP and FFA share a common initial pathobiology, which then bifurcates into two distinct clinical phenotypes, with macrophages possibly playing a key role in phenotype determination. As particularly promising translational research avenues toward direly needed progress in the management of these disfiguring, deeply distressful cicatricial alopecia variants, we advocate to focus on the development of bulge IP and epithelial SC protectants such as, for example, topically effective, HF‒penetrating and immunoinhibitory preparations that contain tacrolimus, peroxisome proliferator-activated receptor-γ, and/or CB1 agonists.

Hair Follicle Grafting Therapy Promotes Re-Emergence of Critical Skin Components in Chronic Nonhealing Wounds.

An exploding public health crisis is the exponential growth in the incidence of chronic nonhealing ulcers associated with diseases such as diabetes. Various modalities have been developed to stimulate wound closure that is otherwise recalcitrant to standard clinical treatments. However, these approaches primarily focus on the process of re-epithelialization and are often deficient in regenerating the full spectrum of structures necessary for normal skin function. Autologous hair follicle grafting is a recent therapy to stimulate the closure of such nonhealing wounds, and we observed effects beyond the epidermis to other important components of the dermis. We found that hair follicle grafting facilitated the reappearance of various undifferentiated and differentiated layers of the epidermis with the restoration of epidermal junctions. In addition, other important structures that are critical for cutaneous health and function such as the blood and lymph vasculature, nerve fibers, and sweat gland structures were restored in postgrafted wounds. Interestingly, both immune cells and inflammatory signals were substantially decreased, indicating a reduction in the chronic inflammation that is a hallmark of nonhealing wounds. Our observation that punch wounds created on the postgrafted area likewise healed suggests that this is a self-sustaining long-term therapy for patients with chronic wounds.

Innovative trends and perspectives for erectile dysfunction treatment: A systematic review.

OBJECTIVE: To review contemporary knowledge concerning the innovative trends and perspectives in the treatment of erectile dysfunction (ED). METHODS: Medline was reviewed for English-language journal articles between January 2000 and March 2016, using the terms 'erectile dysfunction treatments', 'new trends' and 'perspectives'. In all, 114 original articles and 16 review articles were found to be relevant. Of the 76 cited papers that met the inclusion criteria, 51 papers had level of evidence of 1a-2b, whilst 25 had level of evidence of 3-4. Criteria included all pertinent review articles, randomised controlled trials with tight methodological design, cohort studies, and retrospective analyses. We also manually reviewed references from selected articles. RESULTS: Several interesting studies have addressed novel phosphodiesterase type 5 inhibitors (PDE5Is), orodispersible tablets, their recent chronic use, and combination with other agents. A few controlled studies have addressed herbal medicine as a sole or additional treatment for ED. Experimental studies and exciting review papers have addressed stem cells as novel players in the field of ED treatment. Other recent articles have revised the current status of low-intensity extracorporeal shockwave therapy in the field of ED. A few articles without long-term data have addressed new technologies that included: external penile support devices, penile vibrators, tissue engineering, nanotechnology, and endovascular tools for ED treatment. CONCLUSIONS: The current treatment of ED is still far from ideal. We expect to see new drugs and technologies that may revolutionise ED treatment, especially in complex cases.

High Dose Chemotherapy Using CD34+ Hematopoietic Stem Cells / 대한혈액학회지

BACKGROUND: Recently, CD34 antigen expressed on hematopoietic stem cells which is not detected on non-Hodgkin lymphoma (NHL), multiple myeloma and most solid tumors, is identified. In autologous bone marrow transplantation (BMT), positive selection of CD34+ cells may be used to provide hematopoietic stem cells capable of engraftment but depleted of tumor cells. And it can be used to depletion of T lymphocytes to prevent the graft versus host disease (GVHD) in allogeneic BMT. So we performed this study to evaluate the efficacy of purification of CD34+ stem cells with CEPRATE SC Stem Cell Concentration System (CellPro Inc.) and to assess the influence of CD34+ stem cells on engraftment. METHODS: Peripheral blood stem cells were mobilized with cyclophosphamide (except one patient with malignant lymphoma) and G-CSF and harvested using CS-3000 (Fenwall). CD34+ stem cells counted by FACScan (Becton-Dickinson). The conditioning regimens were ICE (Ifosphamide/Carboplatin/Etoposide) in breast cancer, high dose melphalan in multiple myeloma, BEAC (BCNU/Etoposide/Ara-C/Cyclophosphamide) in NHL, TBI (total body irradiation) with cyclophosphamide in acute lymphocytic leukemia (ALL) and busulfan with cyclophosphamide in myelodysplastic syndrome (MDS). We used G-CSF (10 microgram/kg) after transplantation in all patients. RESULTS: Eleven patients, six with high risk or metastatic breast cancer, one with refractory multiple myeloma, one with acute lymphocytic leukemia (transformed from lymphoblasticlymphoma), two with relapsed malignant lymphoma, one with myelodysplastic syndrome (HLA one-locus mismatched allogeneic BMT case, for T lymphocyte depletion) were treated. Hematopoietic stem cells were harvested from autologous peripheral blood in all patients except one patient with MDS whose stem cells were harvested from allogeneic bone marrow. Median duration and number of peripheral blood stem cell (PBSC) harvest were 15 days (13~22) and 3 times (2~8), respectively. The mean number of total stem cells and CD34+ stem cells harvested per pheresis were 204.8 (17.4~797.9)x106/kg and 3.0 (0.3~11.9)x106/kg, respectively. The mean efficacy of CD34+ hematopoietic stem cell selection by CEPRATE SC Stem Cell Concentration System was 47.7% (1.4~99.0%). The number of infused CD34+ stem cells per patient ranged from 0.34 to 4.8x106/kg (mean 2.3x106/kg). After transplantation, the median day of achieving granulocyte counts of >0.5x109/L was 10.5 days and platelet counts of >50x109/L was 14 days. CONCLUSION: CD34+ stem cells separated with CEPRATE SC Stem Cell Concentration System provided reliable and timely hematopoietic reconstitution.