Kulkarni Shilpa, Wang Timothy C, Guha Chandan
Department of Radiation Oncology, Albert Einstein College of Medicine, NY.
Division of Digestive and Liver Diseases, Department of Medicine, Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Curr Pathobiol Rep. 2016 Dec;4(4):221-230. doi: 10.1007/s40139-016-0114-6. Epub 2016 Sep 7.
Therapeutic exposure to high doses of radiation can severely impair organ function due to ablation of stem cells. Normal tissue injury is a dose-limiting toxicity for radiation therapy (RT). Although advances in the delivery of high precision conformal RT has increased normal tissue sparing, mitigating and therapeutic strategies that could alleviate early and chronic radiation effects are urgently needed in order to deliver curative doses of RT, especially in abdominal, pelvic and thoracic malignancies. Radiation-induced gastrointestinal injury is also a major cause of lethality from accidental or intentional exposure to whole body irradiation in the case of nuclear accidents or terrorism. This review examines the therapeutic options for mitigation of non-hematopoietic radiation injuries.
We have developed stem cell based therapies for the mitigation of acute radiation syndrome (ARS) and radiation-induced gastrointestinal syndrome (RIGS). This is a promising option because of the robustness of standardized isolation and transplantation of stromal cells protocols, and their ability to support and replace radiation-damaged stem cells and stem cell niche. Stromal progenitor cells (SPC) represent a unique multipotent and heterogeneous cell population with regenerative, immunosuppressive, anti-inflammatory, and wound healing properties. SPC are also known to secrete various key cytokines and growth factors such as platelet derived growth factors (PDGF), keratinocyte growth factor (KGF), R-spondins (Rspo), and may consequently exert their regenerative effects via paracrine function. Additionally, secretory vesicles such as exosomes or microparticles can potentially be a cell-free alternative replacing the cell transplant in some cases.
This review highlights the beneficial effects of SPC on tissue regeneration with their ability to (a) target the irradiated tissues, (b) recruit host stromal cells, (c) regenerate endothelium and epithelium, (d) and secrete regenerative and immunomodulatory paracrine signals to control inflammation, ulceration, wound healing and fibrosis.
高剂量辐射治疗会因干细胞被破坏而严重损害器官功能。正常组织损伤是放射治疗（RT）的剂量限制毒性。尽管高精度适形放疗技术的进步提高了对正常组织的保护，但为了给予根治性放疗剂量，尤其是针对腹部、盆腔和胸部恶性肿瘤，迫切需要能够减轻早期和慢性辐射效应的缓解和治疗策略。在核事故或恐怖主义事件中，辐射引起的胃肠道损伤也是意外或故意全身照射致死的主要原因。本综述探讨减轻非造血性辐射损伤的治疗选择。
我们已开发出基于干细胞的疗法来减轻急性放射综合征（ARS）和辐射诱导的胃肠道综合征（RIGS）。这是一个有前景的选择，因为基质细胞的标准化分离和移植方案稳健，且它们有能力支持和替代受辐射损伤的干细胞及干细胞微环境。基质祖细胞（SPC）是一种独特的多能异质细胞群，具有再生、免疫抑制、抗炎和伤口愈合特性。已知SPC还能分泌各种关键细胞因子和生长因子，如血小板衍生生长因子（PDGF）、角质形成细胞生长因子（KGF）、R- 斯普迪因（Rspo），因此可能通过旁分泌功能发挥其再生作用。此外，分泌囊泡如外泌体或微粒在某些情况下可能成为替代细胞移植的无细胞选择。
本综述强调了SPC对组织再生的有益作用，其能力包括：（a）靶向受辐射组织；（b）募集宿主基质细胞；（c）再生内皮和上皮；（d）分泌再生和免疫调节旁分泌信号以控制炎症、溃疡、伤口愈合和纤维化。
