George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0405, USA.
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3305-10. doi: 10.1073/pnas.0905444107. Epub 2010 Jan 19.
Local or systemic stem cell delivery has the potential to promote repair of a variety of damaged or degenerated tissues. Although various stem cell sources have been investigated for bone repair, few comparative reports exist, and cellular distribution and viability postimplantation remain key issues. In this study, we quantified the ability of tissue-engineered constructs containing either human fetal or adult stem cells to enhance functional repair of nude rat critically sized femoral defects. After 12 weeks, defects treated with cell-seeded polymer scaffolds had significantly higher bone ingrowth and torsional strength compared to those receiving acellular scaffolds, although there were no significant differences between the cell sources. Next, stem cells were labeled with fluorescent quantum dots (QDs) in an attempt to noninvasively track their distribution after delivery on scaffolds. Clear fluorescence was observed at implantation sites throughout the study; however, beginning 7-10 days after surgery, signals were also observed at contralateral sites treated with acellular QD-free scaffolds. Although immunostaining for human nuclei revealed retention of some cells at the implantation site, no human cells were detected in the control limb defects. Additional histological analysis of implantation and control defect tissues revealed macrophages containing endocytosed QDs. Furthermore, QD-labeling appeared to diminish transplanted cell function resulting in reduced healing responses. In summary, augmentation of polymeric scaffolds with stem cells derived from fetal and adult tissues significantly enhanced healing of large segmental bone defects; however, QD labeling of stem cells eliminated the observed therapeutic effect and failed to conclusively track stem cell location long-term in vivo.
局部或全身干细胞递送具有促进多种受损或退化组织修复的潜力。虽然已经研究了各种干细胞来源用于骨修复，但很少有比较报告，细胞分布和植入后的活力仍然是关键问题。在这项研究中，我们定量评估了含有人胎儿或成人干细胞的组织工程构建体增强裸鼠临界尺寸股骨缺损功能修复的能力。12 周后，与接受无细胞支架的缺陷相比，用细胞接种聚合物支架治疗的缺陷具有更高的骨内生长和扭转强度，尽管细胞来源之间没有显着差异。接下来，用荧光量子点 (QD) 标记干细胞，试图在支架上递送后非侵入性地跟踪其分布。在整个研究过程中，在植入部位都可以观察到清晰的荧光；然而，在手术后 7-10 天开始，在接受无细胞 QD 支架治疗的对侧部位也观察到信号。尽管免疫染色显示人核保留了一些细胞在植入部位，但在对照肢体缺陷中未检测到人类细胞。对植入和对照缺陷组织的进一步组织学分析显示含有内吞 QD 的巨噬细胞。此外，QD 标记似乎降低了移植细胞的功能，导致愈合反应减少。总之，用源自胎儿和成人组织的干细胞增强聚合物支架显著增强了大节段骨缺损的愈合；然而，干细胞的 QD 标记消除了观察到的治疗效果，并未能在体内长期明确跟踪干细胞的位置。
