Key result
Any of the six Angptls combined with saturating levels of growth factors stimulated a 3- to 4.5-fold net expansion of mouse hematopoietic stem cells compared to growth factors alone.
Effect estimate: 3- to 4.5-fold net expansion
Angiopoietin-like proteins 1, 2, 3, 4, 6, and 7 synergize with growth factors to significantly enhance the ex vivo expansion of mouse hematopoietic stem cells.
Does not support clinical HSC expansion protocols; leaves open human validation and translation studies.
Recent advances in hematopoietic stem cells (HSCs) expansion by growth factors including angiopoietin-like proteins (Angptls) have opened up the possibility to use HSCs in regenerative medicine. However, the unavailability of true in vitro HSCs expansion by these growth factors has limited the understanding of the cellular and molecular mechanism of HSCs expansion. Here, we report the functional role of mouse Angptls 1, 2, 3, 4, 6 and 7 and growth factors SCF, TPO, IGF-2 and FGF-1 on purified mouse bone-marrow (BM) Lineage(-)Sca-1(+)(Lin-Sca-1(+)) HSCs. The recombinant retroviral transduced-CHO-S cells that secrete Angptls in serum-free medium were used alone or in combination with growth factors (SCF, TPO, IGF-2 and FGF-1). None of the Angptls stimulated HSC proliferation, enhanced or inhibited HSCs colony formation, but they did support the survival of HSCs. By contrast, any of the six Angptls together with saturating levels of growth factors dramatically stimulated a 3- to 4.5-fold net expansion of HSCs compared to stimulation with a combination of those growth factors alone. These findings lead to an understanding of the basic function of Angptls on signaling pathways for the survival as well as expansion of HSCs in the bone marrow niche.
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Akhter et al. (2013) studied Hematopoietic stem cell expansion. Angptls 1, 2, 3, 4, 6 and 7 combined with growth factors (SCF, TPO, IGF-2 and FGF-1) vs. Growth factors alone was evaluated on Net expansion of HSCs (3- to 4.5-fold net expansion). Any of the six Angptls combined with saturating levels of growth factors stimulated a 3- to 4.5-fold net expansion of mouse hematopoietic stem cells compared to growth factors alone.
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