Differential contributions of graft-derived and host-derived cells in tissue regeneration/remodeling after fat grafting.
BACKGROUND
Recent research indicates that the adipose tissue of nonvascularized grafts is completely remodeled within 3 months, although origins of next-generation cells are unclear.


METHODS
Inguinal fat pads of green fluorescent protein mice and wild-type mice were cross-transplanted beneath the scalp. At 1, 2, 4, and 12 weeks after transplantation, grafted fat was harvested, weighed, and analyzed through immunohistochemistry, whole-mount staining, and flow cytometry of cell isolates. Bone marrow of green fluorescent protein mice was transplanted to wild-type mice (after irradiation). Eight weeks later, these mice also received fat grafts, which were analyzed as well.


RESULTS
The majority of host-derived cells detected during remodeling of grafted fat were macrophages (>90 percent at the early stage; 60 percent at 12 weeks). Cell origins were analyzed at 12 weeks (i.e., when completely regenerated). At this point, mature adipocytes were largely derived from adipose-derived stem/stromal cells of grafts. Although vascular wall constituents were chiefly graft derived, vascular endothelial cells originated equally from graft and host bone marrow. Adipose-derived stem/stromal cells of regenerated fat were an admixture of grafted, host nonbone marrow, and host bone marrow cells.


CONCLUSIONS
The above findings underscore the importance of adipose stem/stromal cells in the grafted fat for adipocyte regeneration. Host bone marrow and local tissues contributed substantially to capillary networks and provided new adipose-derived stem/stromal cells. An appreciation of mechanisms that are operant in this setting stands to improve clinical outcomes of fat grafting and cell-based therapies.
Tokyo, Japan From the Departments of Plastic Surgery and Cardiology, University of Tokyo Graduate School of Medicine.
Kentaro
K
Doi
Fusa
F
Ogata
Hitomi
H
Eto
Harunosuke
H
Kato
Shinichiro
S
Kuno
Kahori
K
Kinoshita
Koji
K
Kanayama
Jingwei
J
Feng
Ichiro
I
Manabe
Kotaro
K
Yoshimura
D017667:Adipocytes / Q000637:transplantation*; D000273:Adipose Tissue / Q000637:transplantation*; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002470:Cell Survival; D002678:Chimera / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006085:Graft Survival; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D012038:Regeneration / Q000502:physiology*; D018709:Statistics, Nonparametric; D016378:Tissue Transplantation / Q000009:adverse effects / Q000379:methods; D020858:Tissue and Organ Harvesting