Differentiation, cell fusion, and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stroma.
To investigate stem cell differentiation in response to tissue injury, human mesenchymal stem cells (hMSCs) were cocultured with heat-shocked small airway epithelial cells. A subset of the hMSCs rapidly differentiated into epithelium-like cells, and they restored the epithelial monolayer. Immunocytochemistry and microarray analyses demonstrated that the cells expressed many genes characteristic of normal small airway epithelial cells. Some hMSCs differentiated directly after incorporation into the epithelial monolayer but other hMSCs fused with epithelial cells. Surprisingly, cell fusion was a frequent rather than rare event, in that up to 1% of the hMSCs added to the coculture system were recovered as binucleated cells expressing an epithelial surface epitope. Some of the fused cells also underwent nuclear fusion.
Spees
Jeffrey L
JL
Center for Gene Therapy, Tulane Health Sciences Center, New Orleans, LA 70112, USA.
Olson
Scott D
SD
Ylostalo
Joni
J
Lynch
Patrick J
PJ
Smith
Jason
J
Perry
Anthony
A
Peister
Alexandra
A
Wang
Meng Yu
MY
Prockop
Darwin J
DJ
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D051927:CD24 Antigen; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology*; D004848:Epithelium / Q000378:metabolism*; D000939:Epitopes / Q000737:chemistry; D049452:Green Fluorescent Proteins; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008164:Luminescent Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins; D008648:Mesoderm / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D014466:Ultraviolet Rays
D015703:Antigens, CD; D051927:CD24 Antigen; C497889:CD24 protein, human; D000939:Epitopes; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D012313:RNA