Priming of human bone marrow-derived mesenchymal stromal cells with
various down-stream effectors of the Transforming Growth Factor 1
pathway boosts their hematopoiesis-supportive ability.
Abstract
Mesenchymal stromal cells (MSCs) isolated from various tissues are
frequently used to expand hematopoietic stem/ progenitor cells
(HSCs/HSPCs) in vitro. They are also co-infused with the HSCs to improve
the HSC engraftment. However, the MSCs sourced from non-hematopoietic
tissues could be less efficient in their hematopoiesis-supportive
ability. Likewise, the hematopoiesis-supportive ability of the MSCs is
known to decline after continuous in vitro culture – an unavoidable
manipulation to get clinically relevant cell numbers. Hence, it may be
necessary to boost the hematopoietic-supportive ability of the long-time
cultured MSCs before their clinical applications in hematological
disorders. In my earlier work, I showed that priming of MSCs isolated
from human bone marrow (BMSC) with Transforming Growth Factor β1 (TGFβ1)
boosts their hematopoiesis-supportive ability via activation of AKT-eNOS
pathway. Accordingly, I also demonstrated that priming the BMSCs with
nitric oxide (NO) donors mimics the effect of TGFβ1. Here I show that
brief exposure of human BMSCs to pharmacological modulators of PKC and
intracellular calcium – two downstream participants in the TGFβ1-eNOS
signaling pathway – also boosts their hematopoiesis-supportive ability.
Such an approach comprising priming the BMSCs with pharmacological
compounds for a short duration and briefly exposing the HSCs to them can
be used in clinical settings to improve the efficacy of stem cell
transplantations. This concept would be helpful in other regenerative
medicine protocols after identifying suitable pharmacological modulators
giving desired effects on the target cells.