Differentiation of human bone marrow-derived cells into buccal epithelial cells in vivo: a molecular analytical study.
BACKGROUND
Adult bone marrow-derived (BMD) cells could be used to repair damaged organs and tissues, but the intrinsic plasticity of these cells has been questioned by results of in-vitro studies suggesting that such cells might fuse with other cells giving the appearance of differentiation. We aimed to determine whether fusion events are important in vivo.


METHODS
To test whether BMD cells can colonise an epithelial tissue and differentiate there without fusion, we did in-situ hybridisation with Y and X chromosome probes labelled with 35-sulphur or digoxigenin, or labelled fluorescently. We did immunohistochemistry with anticytokeratin 13 along with fluorescence in-situ hybridisation to identify Y-chromosome positive buccal epithelial cells in cheek scrapings obtained from five females who had received either a bone-marrow transplant or an allogeneic mobilised peripheral-blood progenitor-cell transplant (enriched in CD34+ cells) from male donors.


RESULTS
When examined 4-6 years after male-to-female marrow-cell transplantation, all female recipients had Y-chromosome-positive buccal cells (0.8-12.7%). In more than 9700 cells studied, we detected only one XXXY-positive cell (0.01%) and one XXY cell (0.01%), both of which could have arisen when an XY cell fused with an XX cell.


CONCLUSIONS
Male BMD cells migrate into the cheek and differentiate into epithelial cells, an occurrence that does not depend on fusion of BMD cells to recipient cells. This finding might be an example of transdifferentiation of haemopoietic or stromal progenitor cells. Plasticity of BMD cells could be useful in regenerative medicine.
Tran
Simon D
SD
National Institute of Dental and Craniofacial Research, Gene Therapy and Therapeutics Branch National Institutes of Health, Bethesda, MD 20892-1190, USA. stran@dir.nidcr.nih.gov <stran@dir.nidcr.nih.gov>
Pillemer
Stanley R
SR
Dutra
Amalia
A
Barrett
A John
AJ
Brownstein
Michael J
MJ
Key
Sharon
S
Pak
Evgenia
E
Leakan
Rose Anne
RA
Kingman
Albert
A
Yamada
Kenneth M
KM
Baum
Bruce J
BJ
Mezey
Eva
E
D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics*; D002459:Cell Fusion; D002465:Cell Movement / Q000235:genetics; D002610:Cheek / Q000473:pathology; D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous