Prophylactic application of human adipose tissue-derived products to prevent radiation disorders

Abstract

Background: Radiation therapy is a mainstay treatment for malignancies, but it can induce deterministic adverse effects in surrounding healthy tissues, including atrophy, fibrosis, ischemia, and impaired wound healing. This exploratory study investigated whether prophylactic administration of products containing adipose tissue–derived stem cells immediately after radiotherapy could prevent the development of long-term functional disorders in irradiated tissues. Methods: A total irradiation dose of 40 Gy (10 Gy, four times weekly) was delivered to the dorsal skin of nude mice. Subsequently, a prophylactic treatment with vehicle, fat tissue, stromal vascular fraction, or micronized cellular adipose matrix was injected subcutaneously into the irradiated area. Six months after these prophylactic treatments, a cutaneous punch wound was created to evaluate histologic changes and wound healing. Results: Histologic assessments demonstrated dermal thickening, atrophy, and increased collagen deposits in the subcutaneous fatty layer 6 months after radiotherapy. In addition, wound healing was significantly delayed. The prophylactic treatments with three different types of human adipose tissue–derived products significantly prevented radiation-induced histologic changes and accelerated wound healing compared with the vehicle-treated irradiated group. Conclusions: This is the first study to demonstrate potential for prophylactic treatments after radiotherapy, which could prevent the progression of chronic radiation therapy disorders. The results could have a substantial impact on current anticancer radiotherapies; a next-generation radiation therapy may need to be always combined with a stem cell therapy. Such prophylactic treatments have the potential to improve wound healing of irradiated tissue and clinical outcomes of reconstructive surgery required after cancer radiotherapy. Clinical Relevance Statement: The results of this study suggest that it is clinically possible to prevent the development of radiation disorders using stem cell therapies. This study may provide a new concept of prophylactic treatment, which would be a paradigm shift in radiotherapy.

Discussion: Prophylactic Application of Human Adipose Tissue–Derived Products to Prevent Radiation Disorders

“…In addition, fibrosis, chronic infection, and lymphedema are common. Data from clinical and preclinical work, such as the findings presented in this murine study by Sowa et al, 1 identify fat grafting as a powerful tool in ameliorating some of these chronic effects.…”

Exploring the mechanisms behind autologous lipotransfer for radiation-induced fibrosis: A systematic review

“…and Sowa et al . showed reduced dermal thickness and collagen density in irradiated mice grafted with lipoaspirate, relative to controls [ 52 , 53 ].…”

“…Furthermore, on average a greater wound area underwent successful healing in the microfat/SVF-injected subgroup compared to the microfat-injected subgroup. In the study by Sowa et al ., the SVF-injected subgroup showed reduced periphilin staining relative to the fat-only subgroup [ 53 ].…”

“…Sowa et al . demonstrated MCAMs had similar anti-fibrotic effects to SVF and superior adipogenic capability to fat grafting alone [ 53 ]. In addition, the preparation of MCAMs is less intensive, quicker, and not subject to the same regulations as SVF.…”

Invited Commentary from the Authors of: Sowa, et al. Patient-reported Outcomes After Autologous Fat grafting in Prosthetic Breast Reconstruction: Prospective Cohort Study Using a Multivariate Analysis

“…On the other hand, fat injections can be expected to improve the tissue potential of the graft bed, as mesenchymal stem cells and vascular endothelial cells contained in the aspirated fat improve the potential of the tissue. 4 In fact, there have been clinical reports of increased satisfaction with fat grafting in clinical cases in which radiotherapy was used. 5 Therefore, we think that radiotherapy and fat grafting are not always incompatible.…”