Differentiation and migration properties of human foetal umbilical cord perivascular cells: potential for lung repair.
Mesenchymal stem cells (MSC) have been derived from different cultured human tissues, including bone marrow, adipose tissue, amniotic fluid and umbilical cord blood. Only recently it was suggested that MSC descended from perivascular cells, the latter being defined as CD146⁺ neuro-glial proteoglycan (NG)2⁺ platelet-derived growth factor-Rβ⁺ ALP⁺ CD34⁻ CD45⁻ von Willebrand factor (vWF)⁻ CD144⁻. Herein we studied the properties of perivascular cells from a novel source, the foetal human umbilical cord (HUC) collected from pre-term newborns. By immunohistochemistry and flow cytometry we show that pre-term/foetal HUCs contain more perivascular cells than their full-term counterparts (2.5%versus 0.15%). Moreover, foetal HUC perivascular cells (HUCPC) express the embryonic cell markers specific embryonic antigen-4, Runx1 and Oct-4 and can be cultured over the long term. To further confirm the MSC identity of these cultured perivascular cells, we also showed their expression at different passages of antigens that typify MSC. The multilineage differentiative capacity of HUCPC into osteogenic, adipogenic and myogenic cell lineages was demonstrated in culture. In the perspective of a therapeutic application in chronic lung disease of pre-term newborns, we demonstrated the in vitro ability of HUCPC to migrate towards an alveolar type II cell line damaged with bleomycin, an anti-cancer agent with known pulmonary toxicity. The secretory profile exhibited by foetal HUCPC in the migration assay suggested a paracrine effect that could be exploited in various clinical conditions including lung disorders.
Montemurro
Tiziana
T
Cell Factory, Center of Transfusion Medicine, Cellular Therapy and Cryobiology, Department of Regenerative Medicine, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy.
Andriolo
Gabriella
G
Montelatici
Elisa
E
Weissmann
Gaia
G
Crisan
Mihaela
M
Colnaghi
Maria Rosa
MR
Rebulla
Paolo
P
Mosca
Fabio
F
Péault
Bruno
B
Lazzari
Lorenza
L
D000818:Animals; D000880:Anthraquinones / Q000378:metabolism; D001681:Biological Assay; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation; D048430:Cell Shape; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood / Q000166:cytology*; D005333:Fetus / Q000166:cytology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology*; D010641:Phenotype; D020543:Proteome / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling; D014945:Wound Healing
D000880:Anthraquinones; D015415:Biomarkers; D020543:Proteome; C010078:alizarin