Dynamic cell-cell interactions between cord blood haematopoietic progenitors and the cellular niche are essential for the expansion of CD34+, CD34+CD38- and early lymphoid CD7+ cells
Dynamic cell-cell interactions between cord blood haematopoietic progenitors and the cellular niche are essential for the expansion of CD34+, CD34+CD38- and early lymphoid CD7+ cells
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DOI：
10.1002/term.226
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发表时间：
2010-03-01
影响因子：
3.3
通讯作者：
Cabral, Joaquim M. S.
中科院分区：
文献类型：
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作者：
da Silva, Claudia Lobato;Goncalves, Raquel;Cabral, Joaquim M. S.
造血干/祖细胞(HSCs)的大多数临床应用将受益于它们的体外扩增，以便从可用的供体样本中获得大量具有治疗意义的细胞。我们研究了脐带血(UCB)造血细胞和骨髓间充质干细胞(MSCs)之间的细胞相互作用对UCB CD34(+)浓缩细胞体外扩增和分化潜能的影响。脐血细胞培养：(A)直接接触骨髓间充质干细胞来源的基质层(接触)；(B)由微孔膜隔开(非接触)；或(C)无基质(无基质)。在HSC-MSC共培养中发生了高度动态的培养事件，涉及细胞与细胞之间的相互作用，这在HSC扩增之前。在整个培养过程中[18天]，接触组的细胞总扩张率显著高于非接触组(18d时增加了28037倍)，而非接触组为85.25倍。在无基质培养中，没有观察到明显的细胞扩张。直接接触骨髓间充质干细胞也明显有利于CD34(+)细胞的扩增(接触组和非接触组在第18天分别增加35+/-5倍和7+/-3倍)。此外，CD34(+)CD38(-)细胞在接触培养过程中始终保持较高的比例(第18天8.1+/-1.9%)，高于非接触培养(5.7+/-1.6%)。重要的是，与骨髓MSCs的直接细胞相互作用显著促进了早期淋巴CD7(+)细胞的扩张，与非接触条件相比，产生了相当多的(x3-10)祖细胞数量。这些结果强调了脐带血造血干细胞和骨髓间充质干细胞之间动态的细胞间相互作用对于最大化体外扩增造血干细胞以获得临床上相关的细胞数量的重要性，这些细胞用于多种环境，如骨髓移植或体细胞基因治疗。版权所有(C)2009 John Wiley&Sons，Ltd.
Most clinical applications of haematopoietic stem/progenitor cells (HSCs) would benefit from their ex vivo expansion to obtain a therapeutically significant amount of cells from the available donor samples. We studied the impact of cellular interactions between umbilical cord blood (UCB) haematopoietic cells and bone marrow (BM)-derived mesenchymal stem cells (MSCs) on the ex vivo expansion and differentiative potential of UCB CD34(+)-enriched cells. UCB cells were cultured: (a) directly in contact with BM MSC-derived stromal layers (contact); (b) separated by a microporous membrane (non-contact); or (c) without stroma (no stroma). Highly dynamic culture events occurred in HSC-MSC co-cultures, involving cell-cell interactions, which preceded HSC expansion. Throughout the time in culture [18 days], total cell expansion was significantly higher in contact (fold increase of 280 37 at day 18) compared to non-contact (85 25). No significant cell expansion was observed in stroma-free cultures. CD34(+) cell expansion was also clearly favoured by direct contact with BM MSCs (35 +/- 5- and 7 +/- 3-fold increases at day 18 for contact and non-contact, respectively). Moreover, a higher percentage of CD34(+)CD38(-) cells was consistently maintained during the time in culture under contact (8.1 +/- 1.9% at day 18) compared to noncontact (5.7 +/- 1.6%). Importantly, direct cell interaction with BM MSCs significantly enhanced the expansion of early lymphoid CD7(+) cells, yielding considerably higher (x 3-10) progenitor numbers compared to non-contact conditions. These results highlight the importance of dynamic cell-cell interactions between UCB HSCs and BM MSCs, towards the maximization of HSC expansion ex vivo to obtain clinically relevant cell numbers for multiple settings, such as BM transplantation or somatic cell gene therapy. Copyright (C) 2009 John Wiley & Sons, Ltd.