Cytokine-Dependent Proliferation of Human CD34+ Progenitor Cells in the Absence of Serum Is Suppressed by Their Progeny's Production of Serine Proteinases

Abstract

ABSTRACT

Commentary: Multipotent Mesenchymal Stromal Cell Recruitment, Migration, and Differentiation: What Have Matrix Metalloproteinases Got to Do with It?

“…MSCs are supposed to decide their fate and to give rise to a number of mature cells, not through a long cascade of steps but rather by shifting direction under the guidance of the microenvironment (via paracrine/autocrine mechanisms, through the secretion in the extracellular matrix of biocompounds that can regulate stem cell differentiation through intra‐ and extracellular signaling) [23, 24]. Several extracellular matrix components may coordinately activate or suppress the expression (at RNA and protein levels) of different MMPs that are capable of matrix remodeling (favoring cell migration to a specific tissue or modulating the engraftment of specific cells) [25, –27]. Extracellular matrix (ECM) structural proteins, cytokines, and growth factors, which have the potentiality of interacting with cryptic sites of MMPs [28] may, through a cascade of steps, shift differentiation directions under the guidance of the microenvironment [29].…”

“…It has become clear that both the extracellular matrix and the microenvironment surrounding MSCs are not a mere scaffold but also harbor crytptic biological functions that can be revealed by proteolysis [23, 25, 27]. Moreover, the up‐ or downregulation of MMPs during MSC differentiation [19, 32, 33] may be the biomolecular mirror of MMP/TIMP balance in MSC migration, plasticity, self‐renewal, and pluripotency.…”

Neutrophil Serine Proteases: Future Therapeutic Targets in Patients with Severe Chronic Neutropenia and Leukemia?

“…Goselink et al have investigated the proliferation of normal human bone marrow-derived CD34 ϩ progenitor cells [1]. They report that, in the absence of serum and serine protease inhibitors (such as secretory leukocyte proteinase inhibitor and ␣ 1 -proteinase inhibitor), the proliferation of stem cells is suppressed by neutrophil serine protease family members, the production of which increases when the CD34 ϩ cells are subjected to myeloid differentiation.…”