한빛사논문
Chanutchamon Sutthiwanjampa a,b, Seung Hyun Kang b,c, Mi Kyung Kim b,d, Jin Hwa Choi b,e, Han Koo Kim c, Soo Hyun Woo c, Tae Hui Bae c, Woo Joo Kim f, Shin Hyuk Kang b,c, Hansoo Park a
aSchool of Integrative Engineering, Chung-Ang University, 84 Heukseok-ro, Heukseok-dong, Dongjak-gu, Seoul 06974, Republic of Korea
bCollege of Medicine, Chung-Ang University, 84 Heukseok-ro, Heukseok-dong, Dongjak-gu, Seoul 06974, Republic of Korea
cDepartment of Plastic and Reconstructive Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102 Heukseok-ro, Heukseok-dong, Dongjak-gu, Seoul 06973, Republic of Korea
dDepartments of Pathology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102 Heukseok-ro, Heukseok-dong, Dongjak-gu, Seoul 06973, Republic of Korea
eDepartment of Radiation Oncology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102 Heukseok-ro, Heukseok-dong, Dongjak-gu, Seoul 06973, Republic of Korea
fDepartment of Plastic Surgery, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong-si, Gyeonggi-do 14353, Republic of Korea
Corresponding authors : Shin Hyuk Kang, Hansoo Park
Abstract
Introduction: Post-mastectomy radiotherapy plays a crucial role in breast cancer treatment but can lead to an inflammatory response causing soft tissue damage, particularly radiation-induced capsular contracture (RICC), impacting breast reconstruction outcomes. Adipose-derived stem cells (ADSCs), known for their regenerative potential via paracrine capacity, exhibit inherent radiotolerance. The influence of tumor necrosis factor-alpha (TNF-α) on ADSCs has been reported to enhance the paracrine effect of ADSCs, promoting wound healing by modulating inflammatory responses.
Objective: This study investigates the potential of TNF-α-treated human ADSCs (T-hASCs) on silicone implants to alleviate RICC, hypothesizing to enhance suppressive effects on RICC by modulating inflammatory responses in a radiation-exposed environment.
Methods: In vitro, T-hASCs were cultured on various surfaces to assess viability after exposure to radiation up to 20 Gy. In vivo, T-hASC and non-TNF-α-treated hASC (C-hASCs)-coated membranes were implanted in mice before radiation exposure, and an evaluation of the RICC mitigation took place 4 and 8 weeks after implantation. In addition, the growth factors released from T-hASCs were assessed.
Results: In vitro, hASCs displayed significant radiotolerance, maintaining consistent viability after exposure to 10 Gy. TNF-α treatment further enhanced radiation tolerance, as evidenced by significantly higher viability than C-hASCs at 20 Gy. In vivo, T-hASC-coated implants effectively suppressed RICC, reducing capsule thickness. T-hASCs exhibited remarkable modulation of the inflammatory response, suppressing M1 macrophage polarization while enhancing M2 polarization. The elevated secretion of vascular endothelial growth factor from T-hASCs is believed to induce macrophage polarization, potentially reducing RICC.
Conclusion: This study establishes T-hASCs as a promising strategy for ameliorating the adverse effects experienced by breast reconstruction patients after mastectomy and radiation therapy. The observed radiotolerance, anti-fibrotic effects, and immune modulation suggest the possibility of enhancing patient outcomes and quality of life. Further research and clinical trials are warranted for broader clinical uses.
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