Skin aging is accompanied by hair loss due to impairments in hair follicle (HF) epithelial progenitor cells and their mesenchymal niche. This inductive mesenchyme, called dermal papilla (DP), undergoes progressive cell loss and eventual miniaturization that contributes to HF pathogenesis. Using laser ablation and fate mapping, we show that HF dermal stem cells (hfDSCs) reconstitute the damaged DP and maintain hair growth, suggesting that hfDSC dysfunction may trigger degeneration of the inductive niche. Fate mapping over 24 months revealed progressive hfDSC depletion, and in vivo clonal analysis of aged hfDSCs showed impaired selfrenewal and biased differentiation. Single-cell RNA-seq confirmed hfDSCs as a central precursor, giving rise to divergent mesenchymal trajectories. In aged skin, hfDSCs exhibited senescent-like characteristics, and senescence-associated secretory phenotypes were identified in the aging HF mesenchyme. These results clarify fibroblast dynamics within the HF and suggest that progressive dysfunction within the mesenchymal progenitor pool contributes to age-related hair loss.

Predicting with certainty which cases will develop POI remains elusive.

We think that the available data on adenosine formation suggest the two signals are responsible for adenosine release from cardiac myocytes: (1) the ratio of oxygen supply to demand and (2) agonist-triggered release of extracellular adenine nucleotides. We do not believe that the available data support the oxygen consumption hypothesis. The few studies which allow us to judge the relative importance of these two signals suggest that both hypoxia and sympathetic nerve stimulation release adenosine primarily by decreasing O2 supply:demand. Agonist triggered nucleotide release may be quantitatively important in situations in which decreased O2 supply/demand cannot explain increased release, i.e., isoproterenol and acetylcholine administration.

Cell-based therapies have recently been the focus of much research to enhance skin wound healing. An important challenge will be to develop vehicles for cell delivery that promote survival and uniform distribution of cells across the wound bed. These systems should be stiff enough to facilitate handling, whilst soft enough to limit damage to newly synthesized wound tissue and minimize patient discomfort. Herein, we developed several novel modifiable nanofibre scaffolds comprised of Poly (ε-caprolactone) (PCL) and gelatin (GE). We asked whether they could be used as a functional receptacle for adult human Skin-derived Precursor Cells (hSKPs) and how naked scaffolds impact endogenous skin wound healing. PCL and GE were electrospun in a single facile solvent to create composite scaffolds and displayed unique morphological and mechanical properties. After seeding with adult hSKPs, deposition of extracellular matrix proteins and sulphated glycosaminoglycans was found to be enhanced in composite grafts. Moreover, composite scaffolds exhibited significantly higher cell proliferation, greater cell spreading and integration within the nanofiber mats. Transplantation of acellular scaffolds into wounds revealed scaffolds exhibited improvement in dermal-epidermal thickness, axonal density and collagen deposition. These results demonstrate that PCL-based nanofiber scaffolds show promise as a cell delivery system for wound healing.

There has been much interest in using autologous chondrocytes in combination with scaffold materials to aid in cartilage repair. In the present study, a total of 27 animals were used to compare the performance of matrix-assisted chondrocyte implantation (MACI®) using a collagen sponge as a chondrocyte delivery vehicle, the sponge membrane alone, and empty controls. A total of three distinct types of mechanical analyses were performed on repaired cartilage harvested from horses after 53 weeks of implantation: (1) compressive behavior of samples to measure aggregate modulus (HA) and hydraulic permeability (k) in confined compression; (2) local and global shear modulus using confocal strain mapping; and (3) boundary friction coefficient using a custom-built tribometer. Cartilage defects receiving MACI® implants had equilibrium modulus values that were 70% of normal cartilage, and were not statistically different than normal tissue. Defects filled with Maix™ membrane alone or left empty were only 46% and 51-63% of control, respectively. The shear modulus of tissue from all groups of cartilage defects were between 4 and 10 times lower than control tissue, and range from 0.2 to 0.4 MPa. The average values of boundary mode friction coefficients of control tissue from all groups ranged from 0.42 to 0.52. This study represents an extensive characterization of the mechanical performance of the MACI® grafts implant in a large animal model at 53 weeks. Collectively, these data demonstrate a range of implant performance, revealing similar compressive and frictional properties to native tissue, with inferior shear properties.

Helically cut strips of the wall of small branches of dog superior mesenteric artery were stretched in a stepwise fashion. Tension developed in response to stretch or to a standard stimulus (epinephrine or electricity) was recorded isometrically. The elastic diagram of the vessel is comparable to that reported by other investigators. Contraction in response to a standard stimulus increased with stretch, as much as 100% for a 10% increase in length. The increase in response continued until the strip reached a certain optimal length (variable from strip to strip), after which the response decreased with further stretch. When the strip was released in a stepwise fashion hysteresis was observed. Possible relationships of tension and length at the level of the contractile element are discussed together with ways in which the information presented here may relate to myogenic autoregulation.

No abstract

Response of large and small coronary arteries to nitroglycerin, NaNO2, and adenosine. Am. J. Physiol. 223(l) : 223-228. 1972.-Large (2 mm od) and small (.5 mm od) coronary artery strips were mounted side by side in a muscle bath. KC1 concentration was brought to 35 mM to produce tone and isometric tension was measured. Responses were expressed as the percent of the maximum relaxation caused by calcium-free physiological salt solution. NaNOz and nitroglycerin caused greater relaxation of large vessels than small (P < 0.05). Adenosine caused greater relaxation of small vessels than large vessels (P < 0.05). Depolarization with an isotonic high potassium (100 mM K&04) solution did not reduce the relaxation in response to nitroglycerin or adenosine, suggesting that relaxation can occur without changes in the electrical state of the cell membrane. The effects of adenosine and nitroglycerin on Ca++-induced contraction suggest that the differential effect