Clinical and preclinical approach in AGA treatment: a review of current and new therapies in the regenerative field.

Androgenetic alopecia (AGA) is the most prevalent type of hair loss. Its morbility is mainly psychological although an increased incidence in melanoma has also been observed in affected subjects. Current drug based therapies and physical treatments are either unsuccessful in the long term or have relevant side effects that limit their application.

[Translated article] Efficacy of transplantation of lipoaspired mesenchymal stem cells in the treatment of chronic rotator cuff tears. Experimental model in rats.

Background And Aim: Rotator cuff tears emerge in approximately 30% of the population over 60 years of age. Arthroscopic surgical treatment of these lesions is the treatment of choice, however, despite the improved repair techniques, the rate of re-tears ranges between 11 and 94%. Therefore, researchers seek to improve the biological healing process through the use of different alternatives such as mesenchymal stem cells (MSCs).

Efficacy of transplantation of lipoaspired mesenchymal stem cells in the treatment of chronic rotator cuff tears. Experimental model in rats.

Background And Aim: Rotator cuff tears emerge in approximately 30% of the population over 60 years of age. Arthroscopic surgical treatment of these lesions is the treatment of choice, however, despite the improved repair techniques, the rate of re-tears ranges between 11 and 94%. Therefore, researchers seek to improve the biological healing process through the use of different alternatives such as mesenchymal stem cells (MSCs).

Adverse effects of xenogenic scaffolding in the context of a randomized double-blind placebo-controlled study for repairing full-thickness rotator cuff tears.

Purpose: The purpose of the study was to compare the safety and efficacy of autologous mesenchymal stem cells (MSCs) embedded in a xenogenic scaffold for repairing the supraspinatus tendon.

Methods: This was a randomized, double-blind and placebo-controlled trial evaluating patients with full-thickness rotator cuff tears (Eudra-CT, 2007-007630-19). Effectiveness was evaluated using the Constant score and a visual analogue pain scale (VAS).

Altered Expression of Wnt Signaling Pathway Components in Osteogenesis of Mesenchymal Stem Cells in Osteoarthritis Patients.

Introduction: Osteoarthritis (OA) is characterized by altered homeostasis of joint cartilage and bone, whose functional properties rely on chondrocytes and osteoblasts, belonging to mesenchymal stem cells (MSCs). WNT signaling acts as a hub integrating and crosstalking with other signaling pathways leading to the regulation of MSC functions. The aim of this study was to evaluate the existence of a differential signaling between Healthy and OA-MSCs during osteogenesis.

Efficacy of supraspinatus tendon repair using mesenchymal stem cells along with a collagen I scaffold.

Objectives: Our main objective was to biologically improve rotator cuff healing in an elderly rat model using mesenchymal stem cells (MSCs) in combination with a collagen membrane and compared against other current techniques.

Methods: A chronic rotator cuff tear injury model was developed by unilaterally detaching the supraspinatus (SP) tendons of Sprague-Dawley rats. At 1 month postinjury, the tears were repaired using one of the following techniques: (a) classical surgery using sutures (n = 12), (b) type I collagen membranes (n = 15), and (c) type I collagen membranes + 1 × 106 allogeneic MSCs (n = 14).

Signature of microRNA expression during osteogenic differentiation of bone marrow MSCs reveals a putative role of miR-335-5p in osteoarthritis.

Background: The aim of this study was to evaluate, the existence of a signature of differentially expressed microRNAs (miRNAs) during osteogenic differentiation of bone marrow MSCs from OA and healthy donors and to describe their possible implication in joint regeneration through modulation of molecular mechanisms involved in homeostatic control in OA pathophysiology.

Methods: Following phenotypic assessment of BM-MSCs obtained from OA diagnosed patients (n = 10) and non-OA (n = 10), total small RNA was isolated after osteogenic induction for 1, 10 and 21 days, miRNA profiles were generated using a commercial expression array of 754 well-characterized miRNAs. MiRNAs, with consistent differential expression were selected for further validation by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis.

Selected reaction monitoring assays in mesenchymal stem cells from osteoarthritis patients.

Osteoarthritis (OA) is considered the most prevalent form of arthritis. The aim of this study was to verify potential protein OA biomarkers by applying Selected Reaction Monitoring (SRM) assays to protein extracts obtained from Bone Marrow-Mesenchymal Stem Cells (BM-MSCs) isolated from OA patients. BM aspirates were obtained from the femoral channel of OA patients at the time of surgery and from the femoral channel of hip fracture subjects without OA during hip joint replacement surgery for the treatment of subcapital fracture.

[Study of the role of miRNA in mesenchymal stem cells isolated from osteoarthritis patients].

Objective: MiRNAs act as gene silencers that are involved in the regulation of essential cell functions. miR-335 is involved in regulating cell differentiation processes in progenitor cells. Mesenchymal stem cells (MSCs) are progenitor cells of chondrocytes and osteoblasts responsible for homeostatic maintenance of cartilage and bone.

Expression of human endogenous retrovirus HERV-K18 is associated with clinical severity in osteoarthritis patients.

Objectives: The aim of this study was to evaluate the involvement of human endogenous retrovirus K18 (HERV-K18) in osteoarthritis (OA), by genotyping the HERV-K18 env locus in OA patients and controls, and analysing HERV-K18 RNA expression and its association with OA risk and clinical variables.

Method: We recruited 558 patients with symptomatic OA and 600 controls. We performed the genotyping by TaqMan assays and the analysis of expression by quantitative real-time polymerase chain reaction (qRT-PCR).

Alternative splicing and proteolytic rupture contribute to the generation of soluble IL-6 receptors (sIL-6R) in rheumatoid arthritis.

Objective: To describe the relationship between the two mechanisms involved in sIL6R generation in rheumatoid arthritis (RA).

Method: RA patients were selected from a group of subjects genotyped for the rs8192284 SNP, located at the proteolytic cleavage site of IL-6R. sIL6R and protease levels (ADAM17) were measured and the contribution of alternative splicing in the generation of sIL-6R was evaluated through qRT-PCR.

Combined influence of genetic and environmental factors in age of rheumatoid arthritis onset.

To study the combined effect of both genetic and environmental factors in the age of rheumatoid arthritis onset. Patients (n = 507). Shared epitope characterization was performed using Lifecodes HLA-SSO.

Plasma soluble IL-6 receptor concentration in rheumatoid arthritis: associations with the rs8192284 IL6R polymorphism and with disease activity.

Soluble interleukin-6 receptor α subunit (sIL-6R) is primarily generated by shedding of the membrane-bound form. This process is influenced by the single nucleotide polymorphism rs8192284 (A > C) resulting in an aspartic acid to alanine substitution (D358A) at the proteolytic cleavage site. The aim of this study was to determine whether plasma levels of sIL6R are influenced by the rs8192284 polymorphism in patients with rheumatoid arthritis and to assess the association between plasma sIL-6R levels and disease activity as reflected by anti-CCP status.

Influence of IL6R rs8192284 polymorphism status in disease activity in rheumatoid arthritis.

Objective: To analyze the influence of IL6R rs8192284 polymorphism on the disease activity of rheumatoid arthritis (RA).

Methods: Patients with RA (n = 281) were followed for a median of 4.2 years.

Characteristics of GLP-1 and exendins action upon glucose transport and metabolism in type 2 diabetic rat skeletal muscle.

Exendin-4, a peptide 53% structurally homologous with glucagon-like peptide 1 (GLP-1), is insulinotropic and has an antidiabetic effect even more prolonged than that of GLP-1. Exendin-9 is an antagonist of GLP-1 receptor and action in several cell systems, but shows GLP-1- and exendin-4-agonistic characteristics in human muscle cells and tissue. The action of GLP-1 upon glucose transport and metabolism in muscle is mediated by specific receptors.

GLP-1 signalling and effects on glucose metabolism in myocytes from type 2 diabetic patients.

Changes in the activity of glycogen synthase a and related kinases (phosphatidylinositol-3-kinase, protein kinase B, p44/42 MAP kinases and p70s6 kinase) evoked by GLP-1 in human myocytes from normal subjects were recently implied in the effect of this hormone upon D-glucose transport and glycogen synthesis in the same cells. The major aims of the present study were i) to investigate the possible extension of this knowledge to myocytes obtained from type 2 diabetic patients, ii) to compare in these patients the response to GLP-1, insulin or the structurally related GLP-1 peptides, exendin (1-39)amide and exendin(9-39)amide, and iii) to explore possible differences in the responsiveness to these agents between normal and diabetic subjects. Apart from the much higher basal PI3K activity and impaired response to insulin of p44/42 MAP kinases in the diabetic patients, the changes in enzyme activity caused by either hormone or peptide, although not identical, were essentially comparable.