Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Berlin, Germany.
Cytotherapy. 2012 Oct;14(9):1041-53. doi: 10.3109/14653249.2012.694418. Epub 2012 Jul 5.
Multipotent mesenchymal stromal cells (MSC) secrete soluble factors that stimulate the surrounding microenvironment. Such paracrine effects might underlie the potential benefits of many stem cell therapies. We tested the hypothesis that MSC are able to enhance intrinsic cellular plasticity in the adult rat hippocampus.
Rat bone marrow-derived MSC were labeled with very small superparamagnetic iron oxide particles (VSOP), which allowed for non-invasive graft localization by magnetic resonance imaging (MRI). Moreover, MSC were transduced with lentiviral vectors to express the green fluorescent protein (GFP). The effects of bilateral MSC transplantation on hippocampal cellular plasticity were assessed using the thymidine analogs 5-bromo-2'-deoxyuridine (BrdU) and 5-iodo-2'-deoxyuridine (IdU). Behavioral testing was performed to examine the consequences of intrahippocampal MSC transplantation on locomotion, learning and memory, and anxiety-like and depression-like behavior.
We found that intrahippocampal transplantation of MSC resulted in enhanced neurogenesis despite short-term graft survival. In contrast, systemic administration of the selective serotonin re-uptake inhibitor citalopram increased cell survival but did not affect cell proliferation. Intrahippocampal transplantation of MSC did not impair behavioral functions in rats, but only citalopram exerted anti-depressant effects.
This is the first study to examine the effects of intrahippocampal transplantation of allogeneic MSC on hippocampal structural plasticity and behavioral functions in rats combined with non-invasive cell tracking by MRI. We found that iron oxide nanoparticles can be used to detect transplanted MSC in the brain. Although graft survival was short, intrahippocampal transplantation of MSC resulted in long-term changes in hippocampal plasticity. Our results suggest that MSC can be used to stimulate adult neurogenesis.
多能间充质基质细胞（MSC）分泌可溶性因子，刺激周围的微环境。这种旁分泌作用可能是许多干细胞治疗潜在益处的基础。我们检验了这样一个假设，即 MSC 能够增强成年大鼠海马体中的固有细胞可塑性。
用超顺磁氧化铁颗粒（VSOP）标记大鼠骨髓来源的 MSC，通过磁共振成像（MRI）实现非侵入性的移植定位。此外，MSC 被慢病毒载体转导以表达绿色荧光蛋白（GFP）。通过胸腺嘧啶类似物 5-溴-2'-脱氧尿苷（BrdU）和 5-碘-2'-脱氧尿苷（IdU）来评估双侧 MSC 移植对海马体细胞可塑性的影响。进行行为测试以检查海马体 MSC 移植对内嗅皮层运动、学习和记忆以及焦虑样和抑郁样行为的影响。
我们发现，尽管短期移植物存活，但海马体 MSC 移植会导致神经发生增强。相比之下，选择性 5-羟色胺再摄取抑制剂西酞普兰的系统给药增加了细胞存活，但不影响细胞增殖。海马体 MSC 移植不会损害大鼠的行为功能，但只有西酞普兰具有抗抑郁作用。
这是第一项研究，结合 MRI 的非侵入性细胞追踪，检查海马体同种异体 MSC 移植对大鼠海马体结构可塑性和行为功能的影响。我们发现氧化铁纳米颗粒可用于检测大脑中的移植 MSC。尽管移植物存活时间短，但海马体 MSC 移植会导致海马体可塑性的长期变化。我们的结果表明，MSC 可用于刺激成年神经发生。
