☆ 4.5 Article

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

JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE (2010)

Journal

JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE

Volume 4, Issue 2, Pages 149-158

Publisher

WILEY

DOI: 10.1002/term.226

Keywords

haematopoietic stem/progenitor cells; bone marrow microenvironment; mesenchymal stem cells; ex vivo expansion

Funding

MIT-Portugal Programme
Bioengineering Focus Area
Fundacao para a Ciencia e a Tecnologia, Portugal [SFRH/BD/38719/2007, SFRH/BD/38720/2007]
Fundação para a Ciência e a Tecnologia [SFRH/BD/38720/2007, SFRH/BD/38719/2007] Funding Source: FCT

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Abstract

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.

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Hydrogel-based microenvironment engineering of haematopoietic stem cells

Meng Zhu, Qiwei Wang, Tianning Gu, Yingli Han, Xin Zeng, Jinxin Li, Jian Dong, He Huang, Pengxu Qian

Summary: Haematopoietic Stem cells (HSCs) possess the ability to renew and differentiate into various lineages, which is regulated by the microenvironment. The use of hydrogels in tissue engineering has allowed for the mimicking of the HSC microenvironment in vitro, influencing HSC behavior and ultimately improving HSC acquisition. This review presents the recent advancements in hydrogel-based microenvironment engineering of HSCs and discusses future challenges in basic research and clinical practice.

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