Differential contributions of graft-derived and host-derived cells in tissue regeneration/remodeling after fat grafting

• Published in: Plastic and reconstructive surgery (1963) Vol. 135; no. 6; p. 1607
• Main Authors: Doi, Kentaro, Ogata, Fusa, Eto, Hitomi, Kato, Harunosuke, Kuno, Shinichiro, Kinoshita, Kahori, Kanayama, Koji, Feng, Jingwei, Manabe, Ichiro, Yoshimura, Kotaro
• Format: Journal Article
• Language: English
• Published: United States 01.06.2015
• Subjects: Adipocytes - transplantation; Adipose Tissue - transplantation; Animals; Bone Marrow Transplantation - methods; Cell Survival; Chimera - physiology; Disease Models, Animal; Female; Flow Cytometry; Graft Survival; Immunohistochemistry; Mice; Mice, Inbred C57BL; Random Allocation; Regeneration - physiology; Statistics, Nonparametric; Tissue and Organ Harvesting; Tissue Transplantation - adverse effects; Tissue Transplantation - methods
• ISSN: 1529-4242
• DOI: 10.1097/prs.0000000000001292

Recent research indicates that the adipose tissue of nonvascularized grafts is completely remodeled within 3 months, although origins of next-generation cells are unclear. 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. 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. 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.