Differential Contributions of Graft-Derived and Host-Derived Cells in Tissue Regeneration/Remodeling after Fat Grafting

作者:Doi Kentaro; Ogata Fusa; Eto Hitomi; Kato Harunosuke; Kuno Shinichiro; Kinoshita Kahori; Kanayama Koji; Feng Jingwei; Manabe Ichiro; Yoshimura Kotaro*
来源:Plastic and Reconstructive Surgery, 2015, 135(6): 1607-1617.
DOI:10.1097/PRS.0000000000001292

摘要

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.

  • 出版日期2015-6