Figure 1.

Inflammatory ambiences governing MSC polarization, progenitor development and regulatory cues. Mesenchymal stem cells (MSC) nest together with hematopoietic stem cells (HSC) in a common niche comprising specific structural features such as a high density of blood vessels (BV). There, MSC release bioactive molecules into their microenvironment such as the chemokine CXCL12, interleukin 7 (IL7) angiopoietin-1 (ANG1) or bone sialoprotein 1 (BSP1, also called osteopontin). Ambient factors regarding acute or chronic inflammatory insults confound the MSCs’ activity to

• (i)
  secrete indoleamine 2,3-dioxygenase (IDO), interleukin 6 (IL6), interleukin 8 (IL8), interleukin 10 (IL10), prostaglandin E-2 (PGE₂), transforming growth factor beta (TGFβ) after activation of toll-like receptors 3 or 4 (TLR3, TLR4) to act on immune cells (IC) to trigger specific T helper (Th) cell responses;
• (ii)
  to convey under low or transient inflammatory stimuli the differentiation of osteoblasts (OB) while at the same time checking progression of adipogenic cells (AC); contrastingly within a chronically inflamed periphery, the osteogenic fate of MSC progeny is stalled and adipogenic differentiation upholstered; the latter further propagate an inflammatory milieu through further excretion of tumor necrosis factor alpha (TNFα) or adiponectin;
• (iii)
  to support the emergence and diversity of hematopoietic precursor cells (HPC) through strong osseous structures in a protected environment while stem cell proximities destined to degenerate by adipose outgrowth hinder the advent of HPC formation.

Deteriorating long-lasting chronic inflammation is frequently observed in biological communication systems at advanced age, for which the frequently used expression ‘inflamm-aging’ has been coined.