Identification and Evaluation of New Immunoregulatory Genes in Mesenchymal Stromal Cells of Different Origins: Comparison of Normal and Inflammatory Conditions.
BACKGROUND Mesenchymal stromal cells (MSCs) possess potent immunomodulatory properties that increase their value as a cell-based therapeutic tool for managing various immune-based disorders. Over the past years, accumulated results from trials using MSCs-based therapy have shown substantial contradictions. Although the reasons underlying these discrepancies are still not completely understood, it is well known that the immunomodulatory activities mediated by distinct MSCs differ in a manner dependent on their tissue origin and adequate response to inflammation priming. Thus, characterization of new molecular pathway(s) through which distinct MSC populations can exert their immunomodulatory effects, particularly during inflammation, will undoubtedly enhance their therapeutic potential. MATERIAL AND METHODS After confirming their compliance with ISCT criteria, quantitative real time-PCR (qRT-PCR) was used to screen new immunoregulatory genes in MSCs, derived from adipose tissue, foreskin, Wharton's jelly or the bone-marrow, after being cultivated under normal and inflammatory conditions. RESULTS FGL2, GAL, SEMA4D, SEMA7A, and IDO1 genes appeared to be differentially transcribed in the different MSC populations. Moreover, these genes were not similarly modulated following MSCs-exposure to inflammatory signals. CONCLUSIONS Our observations suggest that these identified immunoregulatory genes may be considered as potential candidates to be targeted in order to enhance the immunomodulatory properties of MSCs towards more efficient clinical use.
Institute of Molecular Biology and Medicine, Université Libre de Bruxelles (ULB), Gosselies, Belgium.
Mohammad
M
Fayyad-Kazan
Laboratory of Clinical Cell Therapy, Université Libre de Bruxelles (ULB), Institut Jules Bordet, Brussels, Belgium.
Mehdi
M
Najar
Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences I, Lebanese University, Hadath, Lebanon.
Hussein
H
Fayyad-Kazan
Laboratory of Clinical Cell Therapy, Université Libre de Bruxelles (ULB), Institut Jules Bordet, Brussels, Belgium.
Gordana
G
Raicevic
Laboratory of Clinical Cell Therapy, Université Libre de Bruxelles (ULB), Institut Jules Bordet, Brussels, Belgium.
Laurence
L
Lagneaux
D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology / Q000502:physiology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D052816:Foreskin / Q000166:cytology / Q000276:immunology / Q000502:physiology; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism; D059631:Wharton Jelly / Q000166:cytology / Q000276:immunology / Q000502:physiology
D015703:Antigens, CD; C093224:CD100 antigen; C095202:FGL2 protein, human; D058851:GPI-Linked Proteins; C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C118753:SEMA7A protein, human; D039961:Semaphorins; D005340:Fibrinogen