Endothelial progenitor cells promote efficient ex vivo expansion of cord blood-derived hematopoietic stem/progenitor cells

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• 作者：Qi Qu¹ ; Limin Liu¹ ; Guanghua Chen ; Yang Xu ; Xiaojin Wu ; Depei Wu ; ^{wudepei@medmail.com.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cord blood transplantation ; Endothelial progenitor cells ; Hematopoietic engraftment ; Non-obese diabetic/severe combined immunodeficient mice
• 刊名：Cytotherapy
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：18
• 期：3
• 页码：452-464
• 全文大小：1827 K

文摘

Cord blood (CB) hematopoietic stem cell transplantation has often been limited by the scarcity of stem cells. Therefore, the number of CB hematopoietic stem/progenitor cells (HSPCs) should be increased while maintaining the stem cell characteristics.

Methods

We designed an ex vivo culture system using endothelial progenitor cells (EPCs) as stroma to determine the capacity of expanding CB-HSPCs in a defined medium, the effect on engraftment of the expanded cells in a mouse model and the underlying mechanism.

Results

After 7 days of culture, compared with those cultured with cytokines alone (3.25 ± 0.59), CD34+ cells under contact and non-contact co-culture with EPCs were expanded by 5.38 ± 0.61 (P = 0.003) and 4.06 ± 0.43 (P = 0.025)–fold, respectively. Direct cell-to-cell contact co-culture with EPCs resulted in more primitive CD34+ CD38− cells than stroma-free culture (156.17 ± 21.32 versus 79.12 ± 19.77–fold; P = 0.010). Comparable engraftment of day 7 co-cultured HSPCs with respect to HSPCs at day 0 in nonobese diabetic-severe combined immunodeficiency disease (NOD/SCID) mice was measured as a percentage of chimerism (13.3% ± 11.0% versus 16.0% ± 14.3%; P = 0.750). EPCs highly expressed interleukin 6 (IL6) and angiopoietin 1 (ANGPT1), the hematopoietic- related cytokines. A higher transcriptional level of WNT5A genes in EPCs and co-cultured HSPCs suggests that the activation of Wnt signaling pathway may play a role in HSPCs' expansion ex vivo.

Discussion

These data demonstrated that EPCs improve the CD34+ population but do not compromise the repopulating efficacy of the amplified HSPCs, possibly via cytokine secretion and Wnt signaling pathway activation.