Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment

Abstract

Key Points Connective tissue growth factor regulates adipogenic differentiation of MSCs. Connective tissue growth factor regulates leukemia engraftment.

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis

“…Ctgf is highly expressed in bone marrow stromal cells. [21][22][23][24][25][26] , our studies demonstrate that CTGF exerts a regulatory role on B lymphopoiesis.…”

“…However, we showed that Ctgf is highly expressed in BM stromal cells from adult and newborn mice, a finding supported by three recently published studies examining mouse and human BM stromal cells as well as human mesenchymal stem cells. 26,41,42 Fractionation of BM stromal cells further indicated a broad distribution of Ctgf in the BM microenvironment, with CAR cells displaying the highest level of expression. BM stromal cells play a vital role in microenvironmental niches and, reticular cells form stagespecific cellular niches for early B-cell development.…”

“…21 Moreover, high levels of CTGF expression in ALL are linked to poor outcome in patients 22,24 and a recent study suggested that CTGF promotes leukemia cell engraftment and growth in the BM. 26 To date, at least 21 different types of cancer have been associated with either low or high CTGF expression, and linked to distinct clinical outcomes.27 …”

AML-induced osteogenic differentiation in mesenchymal stromal cells supports leukemia growth

“…Arrow points towards cells expressing osterix or RUNX2. We previously demonstrated that AML-MSCs lack the ability to differentiate into adipocytes (22). However, their ability to differentiate into other lineages, including osteogenic or chondrogenic lineages, is not known.…”

“…We previously reported that AML-MSCs lack the capacity to differentiate into functional adipocytes (22). To extend these observations, we cultured AMLMSCs and N-MSCs in adipogenic differentiation induction medium; RNA was extracted from the cells on days 0, 7, 14, and 21 during differentiation, and expression of aP2, PPARγ, and lipoprotein lipase was determined by qRT-PCR.…”