Therapeutic potential of non-adherent BM-derived mesenchymal stem cells in tissue regeneration.
We demonstrated that non-adherent BM cells (NA-BMCs) can be expanded in suspension and give rise to multiple mesenchymal phenotypes including fibroblastic, osteoblastic, chondrocytic and adipocytic as well as glial cell lineages in vitro using the 'pour-off' BMC culture method. Mesenchymal stem cells (MSCs) derived from NA-BMCs (NA-MSCs) from wild-type mice were transplanted into VDR gene knockout (VDR(-/-)) mice that had received a lethal dose of radiation. Results revealed that NA-MSC can be used to rescue lethally irradiated mice and become incorporated into a diverse range of tissues. After lethal dose irradiation, all untransplanted mice died within 2 weeks, whereas those transplanted with NA-MSCs were viable for at least 3 months. Transplantation rescued these mice by reconstructing a hematopoietic system and repairing other damaged tissues. WBC, RBC and platelet counts recovered to normal after 1 month, and VDR gene expression was found in various tissues of viable VDR(-/-) recipients. Adult BM harbors pluripotent NA-MSCs, which can migrate in vivo into multiple body organs. In an appropriate microenvironment, they can adhere, proliferate and differentiate into specialized cells of target tissues and thus function in damaged tissue regeneration and repair.
Zhang
Z L
ZL
Calcium Research Laboratory, McGill University Health Centre and Department of Medicine, McGill University, Montreal, Quebec, Canada.
Tong
J
J
Lu
R N
RN
Scutt
A M
AM
Goltzman
D
D
Miao
D S
DS
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D006413:Hematopoietic System / Q000528:radiation effects; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011833:Radiation Injuries, Experimental / Q000628:therapy; D051381:Rats; D011913:Rats, Inbred BB; D018167:Receptors, Calcitriol / Q000235:genetics; D012038:Regeneration / Q000502:physiology*
D018167:Receptors, Calcitriol