Behavior of in situ human native adipose tissue CD34+ stromal/progenitor cells during different stages of repair. Tissue-resident CD34+ stromal cells as a source of myofibroblasts.
CD34+ adipose stromal cells are scattered in the adipose tissue and found in the CD34+ population of the stromal vascular fraction (SVF). This fraction includes adipose-derived stromal/stem/progenitor cells (ASCs), which have attracted considerable attention and show great promise for the future of regenerative medicine. Studies in this field have been undertaken mainly in vitro. In this work, however, we assessed the characteristics of human adipose tissue-resident CD34+ stromal cells in normal conditions and when activated in vivo during inflammatory/repair processes at different stages of evolution. In normal adipose tissue, these cells showed a characteristic location (peri/paravascular and between adipocytes), a fusiform or stellate morphology, long and moniliform processes, and scarce organelles. During inflammatory/repair stages, native CD34+ stromal cells increased in size, proliferated, developed numerous organelles of synthesis, lost CD34 expression, and differentiated into myofibroblasts (αSMA expression and typical ultrastructure). In double-stained sections, cells expressing both CD34 and αSMA were observed. CD34 expression correlated positively with a high proliferative capacity (Ki-67 expression). Conversely, CD34 expression was lost with successive mitoses and with increased numbers of macrophages in the granulation tissue. CD34+ stromal cell behavior varied depending on proximity to (with myofibroblast differentiation) or remoteness from (with activated plump cells conserving CD34 expression) injury. In conclusion, our observations point to human adipose tissue-resident CD34+ stromal cells as an important source of myofibroblasts during inflammatory/repair processes. Moreover, stromal cell activation may occur with or without αSMA expression (with or without myofibroblast transformation) and with loss or persistence of CD34 expression, respectively.
Department of Anatomy, Histology, Pathology and Radiology, Faculty of Medicine, University of La Laguna, Tenerife, Spain.
Lucio
L
Díaz-Flores
Ricardo
R
Gutiérrez
Koldo
K
Lizartza
Miriam González
MG
Goméz
M Del Pino
Mdel P
García
Francisco J
FJ
Sáez
Lucio
L
Díaz-Flores
Juan F
JF
Madrid
D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002648:Child; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism; D014945:Wound Healing; D055815:Young Adult
D018952:Antigens, CD34
CD34; adipose tissue; granulation tissue; macrophages; myofibroblasts; repair; stromal cells