The hematopoietic stem cell: biology and clinical applications

The hematopoietic stem cells (HSCs) are defined as cells that are able of both self-renewal and multilineage reconstitution of the hematopoietic system. Their biological properties and, similarly, the gene regulation, the positive and negative factors of the hematopoietic progenitor cells and the models of the hematopoietic amplification in the murine system are described. The clinical relevance of HCS has been obtained by the characterization and function of the CD34 cell surface molecule. The methods of isolation, selection and purification of HCS, the clinical use (particularly the mobilization of peripheral CD34+ cells) are detailed. Finally the potential advantages and use of HCS in vivo expansion are described.     

Regulatory T cells and tolerogenic dendritic cells: from basic biology to clinical applications

The induction of antigen (Ag)-specific tolerance is critical for the prevention of autoimmunity and maintenance of immune homeostasis. Recently, attention has been focused on induction of active suppression by regulatory T cells (Treg cells). Also, a role for dendritic cells (DCs) in the promotion of peripheral tolerance has been demonstrated by several studies and is the subject of intensive investigation. It is currently believed that the maturation/activation state of DCs might be a control point for the induction of peripheral tolerance through modifications of the activation state of T cells. Several lines of experimental evidence suggest that unique DC subsets or discrete functional states of the DCs might be devoted to the promotion of Treg cell differentiation. The present review summarizes the emerging literature on the developmental origin and function of human Treg cells and tolerogenic/regulatory DCs. Furthermore, clinical implications of these studies for cellular therapy of immune-mediated pathologies are discussed.     

Regenerative biology: a historical perspective and modern applications

Chronic diseases are both common and deadly. Due to the limitations of conventional therapies for chronic diseases such as advanced heart failure and diabetes mellitus, recent interest has been directed towards regenerative medicine. In this review, we examine the history of regenerative biology and emphasize the dynamic and multidisciplinary growth of this field. We highlight the spectrum of adult tissues that have a remarkable regenerative capacity (i.e., skeletal muscle) versus those that have a more limited regenerative capacity (i.e., heart). We further emphasize the use of relevant contemporary models for the study of regenerative biology (i.e., pancreatic regeneration), which highlight both the challenges for this field of study and the potential for regenerative medicine, including the use of cell-based strategies, to revolutionize medical therapies for chronic diseases.     

Fine-needle aspiration cytology of adamantinoma-like Ewing sarcoma: An unusual parotid tumor

Adamantinoma-like Ewing sarcoma (ALES) is a histological subtype of Ewing sarcoma that demonstrates the morphological and immunohistochemical features of the latter, harbors the EWSR1::FLI1 gene fusion, and additionally demonstrates complex epithelial differentiation on morphology and immunohistochemistry. Accurate preoperative diagnosis has potential to inform management and improve patient outcome. Cytomorphology of ALES is not well documented, with available reports showing a spectrum of features. An aspirate from a 30-year-old male with a swelling in right parotid region, interpreted elsewhere as acinic cell carcinoma (ACC), was submitted to us for review. Smears showed dispersed cells and loosely cohesive clusters with scant cytoplasm and large nuclei with focal nuclear molding, prompting a diagnosis of malignant neoplasm, possibly neuroendocrine carcinoma. Cytoplasmic vacuoles and tigroid background were present focally, the former of which had possibly led to interpretation as ACC. No material was available for ancillary tests. Parotidectomy revealed features of ALES. The cytological features of ALES in the parotid overlap with several basaloid and round blue cell neoplasms that are more common at this site. ALES should be considered in all salivary gland aspirates with isomorphic small round or basaloid cells, with or without the presence of squamous differentiation. Rosettes, cytoplasmic vacuoles, and a tigroid background are subtle morphological clues to the diagnosis, which if suspected on cytomorphology, can be confirmed using ancillary techniques.     

Primitive neuroectodermal tumor/Ewing sarcoma of the retina

An 11-year-old boy underwent enucleation of his left eye for an intraocular tumor. Examination showed a small, round blue cell tumor arising in the peripheral retina near the ciliary body. Immunohistochemical stain results were positive for neuron-specific enolase, synaptophysin, cluster of differentiation 99 (CD99), Friend leukemia integration 1, and CD56. Ultrastructural findings included occasional intracytoplasmic dense core granules. Polymerase chain reaction of the tumor showed a Ewing sarcoma/Friend leukemia integration gene fusion product. The tumor was classified as a primitive neuroectodermal tumor/Ewing sarcoma of the retina and should be distinguished from retinoblastoma. To our knowledge, this is the first case of primary primitive neuroectodermal tumor of the retina.     

Dendritic cell derived-exosomes: biology and clinical implementations

Exosomes are nanometer-sized membrane vesicles invaginating from multivesicular bodies and secreted from different cell types. They represent an "in vitro" discovery, but vesicles with the hallmarks of exosomes are present in vivo in germinal centers and biological fluids. Their protein and lipid composition is unique and could account for their expanding functions such as eradication of obsolete proteins, antigen presentation, or "Trojan horses" for viruses or prions. The potential of dendritic cell-derived exosomes (Dex) as cell-free cancer vaccines is addressed in this review. Lessons learned from the pioneering clinical trials allowed reassessment of the priming capacities of Dex in preclinical models, optimizing clinical protocols, and delineating novel, biological features of Dex in cancer patients.     

Triple helical collagen-like peptides: engineering and applications in matrix biology

Collagen, a large insoluble protein with a characteristic triple helical structure, is found as the most prominent component of extracellular matrix. The functions of collagen are not limited to providing mechanical strength to various tissues and organs as a structural protein, as it has been pointed out that collagen exhibits various biological functions through specific interactions with other macromolecules. However, the use of native triple helical collagen is often troublesome because of its insolubility and gelating properties. Instead, triple helical collagen-like peptides have been designed and are used as collagen surrogates in studies on collagen structure, stability, and biological functions including binding to other proteins and cultured cells. This article reviews recent progress in peptide design, synthesis, and the applications of collagen-like peptides in current matrix biology, while emphasizing the advantages of the peptide-based strategy.     

Antinuclear antibodies: clinical applications

One of the common serological hallmarks of autoimmune disorders is the presence of various autoantibodies in the sera of patients affected by these disorders. Antinuclear antibodies (ANA) detection is often needed to aid the diagnosis in several autoimmune disorders. In view of the different methodologies available for their detection, it becomes essential to understand the advantages and pitfalls of each procedure. This brief review discusses some methodological aspects of ANA detection and the clinical relevance of the presence of some of the autoantibodies found in the sera of patients with autoimmune disorders.