Microgravity potentiates stem cell proliferation while sustaining the capability of differentiation

Microgravity potentiates stem cell proliferation while sustaining the capability of differentiation
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DOI:
10.1089/scd.2006.15.921
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发表时间:
2006-12-01
影响因子:
4
通讯作者:
Ide, Toshinori
Ide, Toshinori
中科院分区:
医学3区
文献类型:
--
作者:
Yuge, Louis;Kajiume, Teruyuki;Ide, Toshinori

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三维(3D)回转器是一种产生多向G力的装置,产生平均10(-3)G的环境。在这里,我们报告,与在1G(C组)正常条件下培养的细胞(一周4倍)相比,在3D回转器(CL组)中培养的人间充质干细胞(hMSC)显示出显着的增殖(一周13倍)。流式细胞术显示,培养7天后,与C组相比,CL组CD44/CD29或CD90/CD29双阳性hMSCs数量增加6倍。培养过程中两组细胞的端粒长度保持相同。 C组细胞在培养期间显示II型胶原蛋白和聚集蛋白聚糖的表达水平增加,而CL组细胞显示降低至不可检测的水平。将每组的 hMSC 颗粒移植到软骨缺陷小鼠体内。 CL组的移植物在7天后形成透明软骨,而C组的移植物仅形成含有少量细胞的非软骨组织。这些结果表明,在3D回转器中培养的hMSC具有干细胞的强增殖特性,并且在移植后保留了分化为透明软骨的能力。相反,在 1-G 环境中培养的细胞不保持这些特征。因此,模拟微重力可以提供一个在体外成功扩增干细胞群的环境,而无需添加可能对干细胞衍生移植产生不利影响的培养补充剂。该方法在再生医学和发育生物学方面具有巨大的潜力。
A three-dimensional (3D) clinostat is a device for generating multidirectional G force, resulting in an environment with an average of 10(-3) G. Here we report that human mesenchymal stem cells (hMSCs) cultured in a 3D-clinostat (group CL) showed marked proliferation (13-fold in a week) compared with cells cultured under normal conditions of 1 G (group C) (4-fold in a week). Flow cytometry revealed a 6-fold increase in the number of hMSCs double-positive for CD44/CD29 or CD90/CD29 in group CL after 7 days in culture, compared with group C. Telomere length remained the same in cells from both groups during culturing. Group C cells showed increasing expression levels of type II collagen and aggrecan over the culture period, whereas group CL cells showed a decrease to undetectable levels. Pellets of hMSCs from each group were explanted into cartilage-defective mice. The transplants from group CL formed hyaline cartilage after 7 days, whereas the transplants from group C formed only noncartilage tissue containing a small number of cells. These results show that hMSCs cultured in a 3D-clinostat possess the strong proliferative characteristic of stem cells and retain their ability to differentiate into hyaline cartilage after transplantation. On the contrary, cells cultured in a 1-G environment do not maintain these features. Simulated micro-gravity may thus provide an environment to successfully expand stem cell populations in vitro without culture supplements that can adversely affect stem cell-derived transplantations. This method has significant potential for regenerative medicine and developmental biology.