Adipose-Derived Stromal Cell-Based Therapies for Radiation-Induced Fibrosis

Berry, Charlotte E.; Abbas, Darren; Lintel, Hendrik; Churukian, Andrew; Guo, Jason; Cotterell, Asha C; Parker, J. M. R.; Downer, Mauricio; Longaker, Michael T.; Wan, Derrick C.

doi:10.1089/wound.2022.0103

Cited by 5 publications

(3 citation statements)

References 126 publications

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“…ADSCs are particularly interesting for their relative abundance and the ease of the isolation procedure compared to other MSC subtypes [ 19 , 145 , 146 ]. Regenerative medicine and immune-mediated disorders certainly represent the principal applications for ADSC-based strategies [ 16 , 147 , 148 , 149 , 150 , 151 , 152 ]. As well as for other MSC sources, ADSC therapeutic functions are mostly mediated by the production of extracellular vesicles and the secretion of specific soluble mediators [ 153 , 154 ].…”

Section: Mscs and Wound Healingmentioning

confidence: 99%

Obesity and Wound Healing: Focus on Mesenchymal Stem Cells

Alma

Marconi

Rossi

et al. 2023

Life

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Chronic wounds represent nowadays a major challenge for both clinicians and researchers in the regenerative setting. Obesity represents one of the major comorbidities in patients affected by chronic ulcers and therefore diverse studies aimed at assessing possible links between these two morbid conditions are currently ongoing. In particular, adipose tissue has recently been described as having metabolic and endocrine functions rather than serving as a mere fat storage deposit. In this setting, adipose-derived stem cells, a peculiar subset of mesenchymal stromal/stem cells (MSCs) located in adipose tissue, have been demonstrated to possess regenerative and immunological functions with a key role in regulating both adipocyte function and skin regeneration. The aim of the present review is to give an overview of the most recent findings on wound healing, with a special focus on adipose tissue biology and obesity.

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Section: Mscs and Wound Healingmentioning

confidence: 99%

Obesity and Wound Healing: Focus on Mesenchymal Stem Cells

Alma

Marconi

Rossi

et al. 2023

Life

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“…Collateral skin and soft tissue injury is often noted in both acute and chronic phases of treatment. Skin changes after irradiation may include epidermal thinning, dermal thickening, atrophy of hair follicles/sebaceous glands, hair loss, increased collagen density, and decreased vascularization [ 4 ]. Over time, skin injury may also progress to pathological radiation-induced fibrosis (RIF).…”

Section: Introductionmentioning

confidence: 99%

Single-cell transcriptional analysis of irradiated skin reveals changes in fibroblast subpopulations and variability in caveolin expression

Kameni,

Griffin,

Berry

et al. 2024

Radiat Oncol

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Background Radiation-induced fibrosis (RIF) is an important late complication of radiation therapy, and the resulting damaging effects of RIF can significantly impact reconstructive outcomes. There is currently a paucity of effective treatment options available, likely due to the continuing knowledge gap surrounding the cellular mechanisms involved. In this study, detailed analyses of irradiated and non-irradiated human skin samples were performed incorporating histological and single-cell transcriptional analysis to identify novel features guiding development of skin fibrosis following radiation injury. Methods Paired irradiated and contralateral non-irradiated skin samples were obtained from six female patients undergoing post-oncologic breast reconstruction. Skin samples underwent histological evaluation, immunohistochemistry, and biomechanical testing. Single-cell RNA sequencing was performed using the 10X single cell platform. Cells were separated into clusters using Seurat in R. The SingleR classifier was applied to ascribe cell type identities to each cluster. Differentially expressed genes characteristic to each cluster were then determined using non-parametric testing. Results Comparing irradiated and non-irradiated skin, epidermal atrophy, dermal thickening, and evidence of thick, disorganized collagen deposition within the extracellular matrix of irradiated skin were readily appreciated on histology. These histologic features were associated with stiffness that was higher in irradiated skin. Single-cell RNA sequencing revealed six predominant cell types. Focusing on fibroblasts/stromal lineage cells, five distinct transcriptional clusters (Clusters 0–4) were identified. Interestingly, while all clusters were noted to express Cav1, Cluster 2 was the only one to also express Cav2. Immunohistochemistry demonstrated increased expression of Cav2 in irradiated skin, whereas Cav1 was more readily identified in non-irradiated skin, suggesting Cav1 and Cav2 may act antagonistically to modulate fibrotic cellular responses. Conclusion In response to radiation therapy, specific changes to fibroblast subpopulations and enhanced Cav2 expression may contribute to fibrosis. Altogether, this study introduces a novel pathway of caveolin involvement which may contribute to fibrotic development following radiation injury.

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“…However, patients who receive tumor radiotherapy may experience severe adverse effects due to medical exposure to ionizing radiation. Although fractional radiation and other accurate techniques have been extensively applied in radiotherapy, radiation-induced tissue fibrosis remains a serious concern [1][2][3]. In addition, accidental and occupational exposure to ionizing radiation can also induces tissue damage.…”

Section: Introductionmentioning

confidence: 99%

Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances

Yu,

Xu,

Song

et al. 2023

J Transl Med

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Cancer remains the leading cause of death around the world. In cancer treatment, over 50% of cancer patients receive radiotherapy alone or in multimodal combinations with other therapies. One of the adverse consequences after radiation exposure is the occurrence of radiation-induced tissue fibrosis (RIF), which is characterized by the abnormal activation of myofibroblasts and the excessive accumulation of extracellular matrix. This phenotype can manifest in multiple organs, such as lung, skin, liver and kidney. In-depth studies on the mechanisms of radiation-induced fibrosis have shown that a variety of extracellular signals such as immune cells and abnormal release of cytokines, and intracellular signals such as cGAS/STING, oxidative stress response, metabolic reprogramming and proteasome pathway activation are involved in the activation of myofibroblasts. Tissue fibrosis is extremely harmful to patients' health and requires early diagnosis. In addition to traditional serum markers, histologic and imaging tests, the diagnostic potential of nuclear medicine techniques is emerging. Anti-inflammatory and antioxidant therapies are the traditional treatments for radiation-induced fibrosis. Recently, some promising therapeutic strategies have emerged, such as stem cell therapy and targeted therapies. However, incomplete knowledge of the mechanisms hinders the treatment of this disease. Here, we also highlight the potential mechanistic, diagnostic and therapeutic directions of radiation-induced fibrosis.

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Adipose-Derived Stromal Cell-Based Therapies for Radiation-Induced Fibrosis

Cited by 5 publications

References 126 publications

Obesity and Wound Healing: Focus on Mesenchymal Stem Cells

Obesity and Wound Healing: Focus on Mesenchymal Stem Cells

Single-cell transcriptional analysis of irradiated skin reveals changes in fibroblast subpopulations and variability in caveolin expression

Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances

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