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Fat Grafting Rescues Radiation-Induced Joint Contracture
STEM CELLS ( IF 5.2 ) Pub Date : 2019-12-03 , DOI: 10.1002/stem.3115
Mimi R Borrelli 1 , Nestor M Diaz Deleon 1 , Sandeep Adem 1 , Ronak A Patel 1 , Shamik Mascharak 1 , Abra H Shen 1 , Dre Irizarry 1 , Dung Nguyen 1 , Arash Momeni 1 , Michael T Longaker 1, 2 , Derrick C Wan 1
Affiliation  

The aim of this study was to explore the therapeutic effects of fat grafting on radiation‐induced hind limb contracture. Radiation therapy (RT) is used to palliate and/or cure a range of malignancies but causes inevitable and progressive fibrosis of surrounding soft tissue. Pathological fibrosis may lead to painful contractures which limit movement and negatively impact quality of life. Fat grafting is able to reduce and/or reverse radiation‐induced soft tissue fibrosis. We explored whether fat grafting could improve extensibility in irradiated and contracted hind limbs of mice. Right hind limbs of female 60‐day‐old CD‐1 nude mice were irradiated. Chronic skin fibrosis and limb contracture developed. After 4 weeks, irradiated hind limbs were then injected with (a) fat enriched with stromal vascular cells (SVCs), (b) fat only, (c) saline, or (d) nothing (n = 10/group). Limb extension was measured at baseline and every 2 weeks for 12 weeks. Hind limb skin then underwent histological analysis and biomechanical strength testing. Irradiation significantly reduced limb extension but was progressively rescued by fat grafting. Fat grafting also reduced skin stiffness and reversed the radiation‐induced histological changes in the skin. The greatest benefits were found in mice injected with fat enriched with SVCs. Hind limb radiation induces contracture in our mouse model which can be improved with fat grafting. Enriching fat with SVCs enhances these beneficial effects. These results underscore an attractive approach to address challenging soft tissue fibrosis in patients following RT.

中文翻译:

脂肪移植挽救辐射诱发的关节挛缩

本研究的目的是探讨脂肪移植对辐射引起的后肢挛缩的治疗效果。放射治疗 (RT) 用于缓解和/或治愈一系列恶性肿瘤,但会导致周围软组织不可避免的进行性纤维化。病理性纤维化可能导致疼痛性挛缩,从而限制运动并对生活质量产生负面影响。脂肪移植能够减少和/或逆转辐射引起的软组织纤维化。我们探讨了脂肪移植是否可以提高小鼠受照射和收缩的后肢的可伸展性。照射 60 日龄雌性 CD-1 裸鼠的右后肢。出现慢性皮肤纤维化和肢体挛缩。4 周后,照射后的后肢被注射(a)富含基质血管细胞(SVC)的脂肪,(b)仅脂肪,(c)生理盐水,或 (d) 没有(n = 10/组)。在基线和 12 周内每 2 周测量一次肢体伸展。然后对后肢皮肤进行组织学分析和生物力学强度测试。辐照显着减少肢体伸展,但通过脂肪移植逐渐挽救。脂肪移植还降低了皮肤硬度并逆转了辐射引起的皮肤组织学变化。在注射富含 SVC 的脂肪的小鼠中发现了最大的益处。后肢辐射在我们的小鼠模型中诱导挛缩,可以通过脂肪移植来改善。富含 SVC 的脂肪可增强这些有益效果。这些结果强调了一种有吸引力的方法,可以解决放疗后患者具有挑战性的软组织纤维化问题。然后对后肢皮肤进行组织学分析和生物力学强度测试。辐照显着减少肢体伸展,但通过脂肪移植逐渐挽救。脂肪移植还降低了皮肤硬度并逆转了辐射引起的皮肤组织学变化。在注射富含 SVC 的脂肪的小鼠中发现了最大的益处。后肢辐射在我们的小鼠模型中诱导挛缩,可以通过脂肪移植来改善。富含 SVC 的脂肪可增强这些有益效果。这些结果强调了一种有吸引力的方法,可以解决放疗后患者具有挑战性的软组织纤维化问题。然后对后肢皮肤进行组织学分析和生物力学强度测试。辐照显着减少肢体伸展,但通过脂肪移植逐渐挽救。脂肪移植还降低了皮肤硬度并逆转了辐射引起的皮肤组织学变化。在注射富含 SVC 的脂肪的小鼠中发现了最大的益处。后肢辐射在我们的小鼠模型中诱导挛缩,可以通过脂肪移植来改善。富含 SVC 的脂肪可增强这些有益效果。这些结果强调了一种有吸引力的方法,可以解决放疗后患者具有挑战性的软组织纤维化问题。脂肪移植还降低了皮肤硬度并逆转了辐射引起的皮肤组织学变化。在注射富含 SVC 的脂肪的小鼠中发现了最大的益处。后肢辐射在我们的小鼠模型中诱导挛缩,可以通过脂肪移植来改善。富含 SVC 的脂肪可增强这些有益效果。这些结果强调了一种有吸引力的方法,可以解决放疗后患者具有挑战性的软组织纤维化问题。脂肪移植还降低了皮肤硬度并逆转了辐射引起的皮肤组织学变化。在注射富含 SVC 的脂肪的小鼠中发现了最大的益处。后肢辐射在我们的小鼠模型中诱导挛缩,可以通过脂肪移植来改善。富含 SVC 的脂肪可增强这些有益效果。这些结果强调了一种有吸引力的方法,可以解决放疗后患者具有挑战性的软组织纤维化问题。
更新日期:2019-12-03
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