CD34+ stromal cells/fibroblasts/fibrocytes/telocytes as a tissue reserve and a principal source of mesenchymal cells. Location, morphology, function and role in pathology
L. Díaz-Flores1, R. Gutiérrez1, M.P. García2, F.J. Sáez3, L. Díaz-Flores Jr1, F. Valladares1,4 and J.F. Madrid5
1Department of Anatomy, Pathology, Histology and Radiology, Faculty of Medicine, University of La Laguna, Tenerife, Spain, 2Department of Pathology, Hospiten® Hospitals, Tenerife, Spain, 3Department of Cell Biology and Histology, UFI11/44, School of Medicine and Dentistry, University of the Basque Country, UPV/EHU, Leioa, Spain, 4CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain and 5Department of Cell Biology and Histology, School of Medicine, Regional Campus of International Excellence, “Campus Mare Nostrum” University of Murcia, Murcia, Spain
Offprint requests to: L. Díaz-Flores, Departamento de Patología, Facultad de Medicina, Universidad de La Laguna, Tenerife, Spain. e-mail: fvallapa@ull.es
Summary. We review the morphofunctional characteristics of CD34+ stromal fibroblastic/fibrocytic cells (CD34+ SFCs) and report our observations. We consider the following aspects of CD34+ SFCs: A) The confusing terms applied to this cell type, often combining the prefix CD34 with numerous names, including fibroblasts, fibrocytes, dendrocytes, keratocytes, telocytes and stromal, dendritic, adventitial, supraadventitial, perivascular, paravascular and delimiting cells; B) Changes in their immunophenotype, e.g., loss of CD34 expression and gain of other markers, such as those defining mesenchymal and derivate cells (myofibroblasts, osteoblasts, chondroblasts, adipocytes); C) Morphology (elongated or triangular cell body and thin, moniliform, bipolar or multipolar cytoplasmic processes), immunohistochemistry (co-expression of and changes in molecular expression) and structure (characteristics of nucleus and cytoplasmic organelles, and points of contact and junctions in quiescent and activated stages by light and electron microscopy); D) Location and distribution in the vessels (adventitia or external layer), in the tissues (connective, adipose, blood, muscle and nervous) and in the organs and systems (skin, oral cavity and oropharynx, respiratory, digestive, urinary, male, female, endocrine and lymphoid systems, serosal and synovial membranes, heart, eye and meninges); E) Origin from the mesoderm and cranial neural crest in the embryo, and from stem cells (themselves or other cells) and/or peripheral blood pluripotent stem cells (circulating progenitor cells) in post-natal life; F) Functions, such as synthesis of different molecules, progenitor of mesenchymal cells, immunomodulation, parenchymal regulation (growth, maturation and differentiation of adjacent cells), induction of angiogenesis, scaffolding support of other cells and phagocytic properties. Since CD34+ SFCs are the main reservoir of tissue mesenchymal cells (great mesenchymal potential, probably higher than that proposed for pericytes and other stromal cells), we dedicate a broad section to explain their in vivo behaviour during proliferation and differentiation in different physiologic and pathologic conditions, in addition to their characteristics in the human tissues of origin (adult stem cell niches); G) Involvement in pathological processes, e.g., repair (regeneration and repair through granulation tissue), fibrosis, tumour stroma formation and possible CD34+ SFC-derived tumours (e.g., solitary fibrous tumour, dermato-fibrosarcoma protuberans, giant cell fibroblastoma, nuchal-type fibroma, mammary and extramammary myofibroblastoma, spindle and pleomorphic cell lipoma, and elastofibroma) and H) Clinical and therapeutic implications. Histol Histopathol 29, 831-870 (2014)
Key words: Microscopy, Immunohistochemistry, Origin
DOI: 10.14670/HH-29.831