Transplantation of Human Marrow Stromal Cells and Mono-Nuclear Bone Marrow Cells Into the Injured Spinal Cord A Comparative Study

Transplantation of Human Marrow Stromal Cells and Mono-Nuclear Bone Marrow Cells Into the Injured Spinal Cord A Comparative Study
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DOI:
10.1097/brs.0b013e3181bdca87
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发表时间:
2009-11-15
期刊:
影响因子:
3
通讯作者:
Neuhuber, Birgit
Neuhuber, Birgit
中科院分区:
医学2区
文献类型:
--
作者:
Samdani, Amer F.;Paul, Courtney;Neuhuber, Birgit

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研究设计。两组 6 只大鼠接受背外侧索切开术,然后直接注射骨髓基质细胞 (MSC) 或骨髓单核部分 (mnBM)。 4或21天处死动物。目的。细胞移植是一种有前景的脊髓损伤(SCI)治疗策略;然而,大多数细胞在移植前需要进行培养,这为临床应用带来了繁琐的步骤。立即可用于移植的细胞,如 mnBM,将是更好的选择。背景数据摘要。先前的研究表明,MSC 移植可促进 SCI 后的保护和修复。间充质干细胞由于易于分离且可获得自体来源,因此对移植很有吸引力。 MSC 源自全骨髓,经过纯化并在培养中扩增至少 2 周。或者,mnBM 可用于移植。通过简单离心从骨髓中提取的 mnBM 可在数小时内重新植入;然而,免疫细胞的存在可能会带来问题。方法。将来自人类供体的培养的 MSC 或 mnBM 急性移植到 SCI 中。处死后,对脊髓切片进行组织学分析,分析移植物来源的免疫细胞的存在、宿主免疫反应、组织保留、神经胶质疤痕形成和移植效果。结果。与 MSC 移植动物相比,mnBM 移植到 SCI 后不会产生成熟的免疫细胞,也不会引起宿主免疫反应增加或组织损失。相比之下,间充质干细胞移植后早期宿主巨噬细胞/小胶质细胞反应增加,这可能是由于细胞暴露于含血清培养基所致。 mnBM 移植后第 4 天,神经胶质疤痕不太明显。第 21 天,差异已经消退,MSC 和 mnBM 巨噬细胞的反应以及对神经胶质疤痕的影响具有可比性。 MSC 和 mnBM 植入效率也相似。结论。使用 mnBM 是 MSC 移植到 SCI 的可行替代方案,并且可以极大地简化临床转化。
Study Design. Two groups of 6 rats received dorsolateral funiculotomies followed by direct injection of bone marrow stromal cells (MSC) or mono-nuclear fraction of bone marrow (mnBM). Animals were killed at 4 or 21 days.Objective. Cellular transplantation is a promising treatment strategy for spinal cord injury (SCI); however, most cells need to be cultured before transplantation introducing burdensome steps for clinical application. Cells immediately available for transplantation, like mnBM, would be preferable.Summary of Background Data. Previous studies have shown that MSC transplants promote protection and repair after SCI. MSC are attractive for transplantation because of easy isolation and availability of autologous sources. MSC are derived from whole bone marrow, purified and expanded in culture for a period of at least 2 weeks. Alternatively, mnBM could be used for transplantation. mnBM derived from bone marrow from through simple centrifugation can be reimplantated within hours; however, the presence of immune cells may be problematic.Methods. Cultured MSC or mnBM from human donors were acutely transplanted into SCI. After sacrifice, spinal cord sections were histologically analyzed for presence of graft-derived immune cells, host immune response, tissue sparing, glial scar formation, and grafting efficacy.Results. mnBM did not give rise to mature immune cells after transplantation into SCI, or evoke an increased host immune response or tissue loss compared to MSC-transplanted animals. In contrast, host macrophage/microglia response was increased early after MSC transplantation, perhaps due to exposure of cells to serum-containing media. The glial scar was less prominent after mnBM transplantation at day 4. At 21 days, differences had subsided and MSC and mnBM macrophage responses and effects on glial scarring were comparable. MSC and mnBM engraftment efficiencies were also similar.Conclusion. The use of mnBM is a viable alternative to MSC for transplantation into SCI and may dramatically ease clinical translation.