Kidd S, Spaeth E, Klopp A, Andreeff M, Hall B, Marini F C
Section of Experimental Hematology and Therapy, Department of Stem Cell Transplant and Cellular Therapy, UT-MD Anderson Cancer Center, Houston, Texas, USA.
Cytotherapy. 2008;10(7):657-67. doi: 10.1080/14653240802486517.
Recent progress in the research of mesenchymal stromal cells/multipotent stromal cells (MSC) has revealed numerous beneficial innate characteristics, suggesting potential value in an array of cellular therapies. MSC are easily isolated from bone marrow (BM), fat and other tissues, and are readily propagated in vitro. Transplanted/injected MSC have been shown to migrate to a variety of organs and tissues; however, sites of inflammation and pathology elicit enhanced MSC homing for tissue remodeling and repair. Tumors utilize many of the same inflammatory mediators uncovered in wound healing and likewise provide a site for preferential MSC homing. Although incorporation into the tumor microenvironment is apparent, the role of recruited MSC in the tumor microenvironment remains unclear. Some published studies have shown enhancement of tumor growth and development, perhaps through immunomodulatory and pro-angiogenic properties, while others have shown no apparent effect or have demonstrated inhibition of tumor growth and extended survival. This controversy remains at the forefront as clinical applications of MSC commence in anti-tumor therapies as well as as adjuncts to stem cell transplantation and in ameliorating graft-versus-host disease. Careful analysis of past studies and thoughtful design of future experiments will help to resolve the discrepancies in the field and lead to clinical utility of MSC in disease treatment. This review highlights the current theories of the role of MSC in tumors and explores current controversies.
间充质基质细胞/多能基质细胞(MSC)的研究进展揭示了许多有益的固有特性,表明其在一系列细胞治疗中具有潜在价值。MSC易于从骨髓(BM)、脂肪和其他组织中分离出来,并易于在体外增殖。已证明移植/注射的MSC可迁移至多种器官和组织;然而,炎症和病理部位会引发MSC更强的归巢,以进行组织重塑和修复。肿瘤利用了许多在伤口愈合中发现的相同炎症介质,同样也为MSC优先归巢提供了场所。尽管明显可以融入肿瘤微环境,但招募的MSC在肿瘤微环境中的作用仍不清楚。一些已发表的研究表明,MSC可能通过免疫调节和促血管生成特性促进肿瘤生长和发展,而其他研究则表明没有明显效果或显示出对肿瘤生长的抑制作用以及延长生存期。随着MSC在抗肿瘤治疗、干细胞移植辅助治疗以及改善移植物抗宿主病中的临床应用开始,这一争议仍然是前沿问题。仔细分析过去的研究并精心设计未来的实验将有助于解决该领域的差异,并使MSC在疾病治疗中具有临床实用性。本综述重点介绍了目前关于MSC在肿瘤中作用的理论,并探讨了当前的争议。