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Purpose: To investigate the effect of platelet-rich fibrin as a rich source of growth factors on biomechanical and biochemical aspects of tendon healing. Methods: Tendon defects were created in six adult male mixed breed dogs by surgical resection of the central third of the patellar tendon of both hind limbs. The defects were either treated by platelet-rich fibrin implantation or left empty. The animals were euthanized one, three and six months after surgery and their patellar tendons harvested for determination of ultimate stress, ultimate strain, tensile strength and Young’s modulus of elasticity along with hydroxyproline content. Results: Significant differences were not observed in mean values of the measured biomechanical and biochemical parameters at any time point between the two groups. Conclusions: Based on the results of the present study, PRF did not have a positive influence on biomechanical and biochemical aspects of tendon healing in dogs.

Platelets are blood components with high biomedical potential due to their physiological role in wound healing and their rich growth factor content. This paper describes proof-of-concept experiments aimed to produce a new blood-derived product by applying pulsed electric fields (PEF) to platelet concentrates (PC) with no therapeutic value for transfusion medicine. A human platelet concentrate suspension was subjected to a PEF treatment of 1 pulse, 5kV/cm, for 2$\mu$s. Release of platelet-derived growth factor (PDGF) from the electroporated platelets was measured by ELISA. Furthermore, the biological activity of the obtained blood-derived product was characterized. Human mesenchymal stem cells (hMSC) were cultured in the presence of the proteins released from the platelets after PEF application and evaluated for their expansion potential.

Results show that platelet concentrates subjected to a single PEF treatment can release PDGF to the supernatant. Protein release from the single and transient PEF cycle was confirmed by the expansion of hMSC cultured with a medium supplemented with the platelet releasate obtained from electroporated platelets. These results demonstrate the potential of a new application of PEF for the valorization of PC into a biomedical product with therapeutic value.

Fibrin sealant and platelet gels are human blood-derived, biodegradable, non toxic, surgical products obtained by mixing a fibrinogen concentrate or a platelet rich plasma with thrombin, respectively. Fibrin sealant is now a well known surgical tool increasingly used to stop or control bleeding, or to provide air and fluid tightness in many surgical situations. Platelet gels are newly developed preparations that are of specific interest because they contain numerous physiological growth factors and cytikines that are released upon the activation of blood platelets by thrombin. These growth factors, including PDGF, TGF-β 1, BMP, and VEGF have been shown to stimulate cell growth and differentiation with special clinical benefits for soft and bony tissue healing and regeneration. Platelet gels allow surgeons to manipulate the cellular environment of surgical sites and to guide tissue regeneration. A specific interest of such products is observed for the induction of osteogenesis and chondrogenesis. Advances in the preparation, clinical use, and safety of these two important classes of blood-derived biomaterials are reviewed.

The following sections are included:

• Summary

• Methods Developed to Study Protein Thiols
  • Selective Radioactive Protein Thiol Labeling Reagent N-iodoacetyl-[¹²⁵I]-3-iodotyrosine (IAIT)
  • Arsenical-Based Affinity Chromatography of Vicinal Thiol Proteins
  • Thiol/Disulfide Exchange to Purify Monothiol Proteins
  • Determination of the Redox State of Thiol Proteins in Intact Cells

• Nature and Redox State of Thiol Proteins in Cell Extracts
  • The Majority of Cell Proteins are Present in the Reduced State
  • The Majority of the Cell Thiol Proteins Contain Surface-Localized Vicinal Thiols
  • Properties of Thiol Proteins Oxidized by Reaction with Active Disulfides
  • NADPH-Dependent Protein Disulfide Reductase Activity Depends on the Mixed Disulfide Formed by Thioredoxin
  • Implications of the Studies in vitro with Oxidized Cell Extracts

• Redox Regulation during Growth Initiation⁹
  • Growth Factors Induce a Calcium-Dependent Transient Oxidation of TXN and Other Cell Proteins⁹
  • Calcium Inhibits the in vitro Activity of Thioredoxin Reductase⁹
  • Implications of the Transient Oxidation of Thioredoxin and Other Cell Dithiol Proteins

• Concluding Remarks

• Acknowledgments

• References

Myocardial infarction is the leading cause of chronic heart failure, an ominous disease entity with a wide prevalence in many countries. The morbidity and mortality of chronic heart failure remains high, despite recent pharmacologic advances and cardiac resynchronization therapy. After acute coronary occlusion, the necrotic area triggers a cascade of pathophysiologic events that may lead to structural and electrophysiological left ventricular remodeling, and eventually to progressive chronic heart failure. Therapeutic strategies targeting the repair of the infarcted myocardium aim at interrupting this vicious cycle and constitute an etiological and, as such, promising approach. However, after the initial enthusiasm accompanying early reports, subsequent preclinical and clinical studies unveiled several challenges associated with cell survival and proliferation, as well as abnormal electrophysiological responses after engraftment. In this chapter, we review the main cell sources that hold promise for clinical use, either alone or combined with growth factors and biomaterials, focusing on the acute and medium-term electrophysiological effects of cardiac regeneration approaches.

New data have recently accumulated on how stem cell behave, self-renew and differentiate. Many studies have also focused on defining stem cells, and determination of the properties, including the mode of cell division and polarity, and regulatory environment(s) of both embryonic and tissue-specific stem cells in the last decades. In the lung, recent data show evidences that lung epithelial stem and progenitor cells are polarized, highly mitotic, have characteristic perpendicular cell divisions, and show a mode of division that is similar to other systems. They further show that the asymmetric division is probably the common mode of division in the mitotically dividing distal epithelial stem and progenitor cells of the embryonic lung. Both symmetric and asymmetric mode of cell divisions are tightly regulated in different stem cell types during tissue development and morphogenesis. How to choose between a symmetric and asymmetric cell division is one of the major questions in the stem cell field. It largely affects tissue development, morphogenesis and disease in different organs since improper asymmetric divisions badly affect organ morphogenesis, whereas uncontrolled symmetric division can lead to tumor formation. Moreover, the proper balance between self-renewal and differentiation of lung epithelial stem and progenitor cells is absolutely required for maintaining normal lung morphogenesis and for lung repair and regeneration since a deficiency of this balance probably can lead to a premature or injured lung. Therefore, identification of lung-specific stem cell types, understanding their behavior, and how they balance their self-renewal and differentiation could lead to the identification of innovative solutions for restoring normal lung morphogenesis and/or regeneration and repair of the lung. Furthermore, understanding the molecular mechanisms that control the asymmetrical cell division and both cell polarity and fate of lung epithelial stem and progenitor cells can help identifying new targets for prevention and rescuing lethal lung diseases in infants and children, and for regeneration of injured lungs. In this chapter, we will discuss recently accumulated data on the lung cell polarity, and the mode of division of lung epithelial stem and progenitor cells. In addition, we will describe the functions of Numb in stem cell fate and mode of division, and compare cell polarity and mode of division in the lung stem cells with other systems, as well as discuss the regulatory mechanisms of lung stem cell polarity, fate, behavior and mode of division.