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Adipocyte Stem Cells Ameliorate Total Body Irradiation Induced Hematopoietic Syndrome and Late Radiation Fibrosis
M. Asher Schusterman II, Asim Ejaz, Michael Epperly, Renee Fisher, Xichen Zhang, Moriah Johngrass, Lauren Kokai, Joel Greenberger, J. Peter Rubin
UPMC
2019-02-14
Presenter: M. Asher Schusterman II
Affidavit:
This is the original work of the resident
Director Name: Vu T. Ngueyn
Author Category: Resident Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Background: This study sought to elucidate the cellular and molecular mechanisms involved in adipose stem cell (ASC) amelioration of radiation fibrosis (RF).
Methods: Transwell co-cultures were made with a bottom layer of irradiated human foreskin fibroblasts (HFFs) and mouse cell lines, with an upper layer of mouse or human ASCs. We quantitated fibrosis-related gene transcripts in lower layer cells and regulatory cytokines in upper layer cells by quantitative real time (qRT) PCR. 24 female mice received 9.25 Gy total body irradiation (TBI). The treatment group (n=12) received intraperitoneal injection of ASCs at 24 hours while control (n=12) received saline. Other female C57BL/6J mice received 35Gy radiation to right hind limb. Half received an injection of mouse ASCs to the limb. Fibrosis was quantitated by histologic staining for collagen and range of limb motion measurements.
Results: Transwell coculture revealed significant down regulation of profibrotic genes (TGF β, and Col 1-4) in irradiated cells. Hepatocyte growth factor (HGF) was prominently expressed in upper layer ASCs. Adding HGF to irradiated HFFs significantly down regulated pro-fibrotic gene transcripts. Intraperitoneal injection of ASCs 24 hrs after TBI significantly increased survival at 30 days (p = 0.047). At day 28 post-radiation, irradiated limb excursion was 11.4o ± 2.7o compared to 57.0o ± 2.5o (p < 0.0001) in the contralateral non-irradiated limb. Irradiated limbs that had received ASC injection had significantly increased excursion (42.5o ± 2.5o; p = 0.0013) at day 28.
Conclusion: ASCs ameliorate TBI lethality and reduce RF in vitro and in vivo via HGF.
