The tissue specific nature of mesenchymal stem/stromal cells: gaining better understanding for improved clinical outcomes

Mesenchymal stem/stromal cells (MSCs) are multipotent progenitors that are derived from most adult tissue as well as cord blood and placenta. MSCs are defined by their adherent nature, ability to propagate in culture and capacity to differentiate into bone fat and cartilage. However, many studies have shown that MSCs, derived from different tissues, differ both in their in situ and in vitro phenotypes. Despite abundance of MSCs studies, little is known about the molecular events that control their tissue specific nature. Two recent studies comparing MSCs derived from different tissues have now found clues to the molecular mechanisms that control the tissue specific nature ofthese cells. In the first, the superior genomic stability of adipose derived MSCs (ASCs), compared to bone marrow (BM) MSCs, was explained by reduced H19, a long non-coding RNA expression and increased p53 activity of ASCs. In the second, a compression of abdominal and subcutaneous ASCs reveals poor propagation, differentiation and migration capacities of abdominal ASCs that is explained by their increased tendency to over-accumulate reactive oxygen species (ROS) in culture. ROS over production in abdominal ASCs was shown to be controlled by the NADPH oxidase NOX1. The unique features of MSCs derived from different tissues suggest a tissue specific molecular signature arising from the tissue of origin that is retained during culture. The implications of this phenomenon on our understanding of the role and function of MSCs in situ as well as on their clinical utilization, is discussed

The Hemopoietic Stem Cell Niche Versus the Microenvironment of the Multiple Myeloma-Tumor Initiating Cell

Multiple myeloma cells are reminiscent of hemopoietic stem cells in their strict dependence upon the bone marrow microenvironment. However, from all other points of view, multiple myeloma cells differ markedly from stem cells. The cells possess a mature phenotype and secrete antibodies, and have thus made the whole journey to maturity, while maintaining a tumor phenotype. Not much credence was given to the possibility that the bulk of plasma-like multiple myeloma tumor cells is generated from tumor-initiating cells. Although interleukin-6 is a major contributor to the formation of the tumor’s microenvironment in multiple myeloma, it is not a major factor within hemopoietic stem cell niches. The bone marrow niche for myeloma cells includes the activity of inflammatory cytokines released through osteoclastogenesis. These permit maintenance of myeloma cells within the bone marrow. In contrast, osteoclastogenesis constitutes a signal that drives hemopoietic stem cells away from their bone marrow niches. The properties of the bone marrow microenvironment, which supports myeloma cell maintenance and proliferation, is therefore markedly different from the characteristics of the hemopoietic stem cell niche. Thus, multiple myeloma presents an example of a hemopoietic tumor microenvironment that does not resemble the corresponding stem cell renewal niche

p53 Plays a Role in Mesenchymal Differentiation Programs, in a Cell Fate Dependent Manner

Background: The tumor suppressor p53 is an important regulator that controls various cellular networks, including cell differentiation. Interestingly, some studies suggest that p53 facilitates cell differentiation, whereas others claim that it suppresses differentiation. Therefore, it is critical to evaluate whether this inconsistency represents an authentic differential p53 activity manifested in the various differentiation programs. Methodology/Principal Findings: To clarify this important issue, we conducted a comparative study of several mesenchymal differentiation programs. The effects of p53 knockdown or enhanced activity were analyzed in mouse and human mesenchymal cells, representing various stages of several differentiation programs. We found that p53 downregulated the expression of master differentiation-inducing transcription factors, thereby inhibiting osteogenic, adipogenic and smooth muscle differentiation of multiple mesenchymal cell types. In contrast, p53 is essential for skeletal muscle differentiation and osteogenic re-programming of skeletal muscle committed cells. Conclusions: These comparative studies suggest that, depending on the specific cell type and the specific differentiatio

À la recherche d’une définition moléculaire plus que descriptive pour les cellules souches

Le terme cellule souche désigne un groupe très hétérogène de cellules qui, contrairement aux cellules différenciées qu’elles engendrent, ne peuvent pas être identifiées par une signature moléculaire caractéristique. Cette absence d’une définition moléculaire commune à toutes les cellules souches explique qu’on se contente depuis des décennies d’une définition descriptive, fondée sur leur potentiel plus que sur les fonctions qu’elles effectuent réellement. Il en résulte une certaine confusion qui entretient des controverses parfois inutiles dans ce champ scientifique. En m’appuyant sur l’exemple des cellules souches mésenchymateuses, je discute dans cette revue les différentes données qui fondent les incertitudes actuelles, et tente de proposer une nouvelle définition de l’« état souche » et de son instabilité qui pourrait faire consensus

Restrictins: Stromal cell associated factors that control cell organization in hemopoietic tissues

Hemopoiesis is a sequence of events initiated by the self-renewal of pluripotent stem cells followed by a series of differentiation steps and completed in the formation of distinct tissue patterns. Differentiation and self-renewal are antagonistic processes. A mechanism that attenuates the differentiation flow is obligatory to prevent the exhaustion of the stem cell pool. We suggest that stromal cells from the bone marrow control stem cell renewal through a mechanism that does not require colony-stimulating factors. The organization of cells within the tissue and their specific localization is suggested to be directed by stromal cell activities other than differentiation inducers. These stromal cell activities restrict differentiation or accumulation of mature cells. They are therefore designated as 'Restrictins'.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The tissue specific nature of mesenchymal stem/stromal cells: gaining better understanding for improved clinical outcomes: DOI: 10.14800/rd.780

Mesenchymal stem/stromal cells (MSCs) are multipotent progenitors that are derived from most adult tissue as well as cord blood and placenta. MSCs are defined by their adherent nature, ability to propagate in culture and capacity to differentiate into bone fat and cartilage. However, many studies have shown that MSCs, derived from different tissues, differ both in their in situ and in vitro phenotypes. Despite abundance of MSCs studies, little is known about the molecular events that control their tissue specific nature. Two recent studies comparing MSCs derived from different tissues have now found clues to the molecular mechanisms that control the tissue specific nature ofthese cells. In the first, the superior genomic stability of adipose derived MSCs (ASCs), compared to bone marrow (BM) MSCs, was explained by reduced H19, a long non-coding RNA expression and increased p53 activity of ASCs. In the second, a compression of abdominal and subcutaneous ASCs reveals poor propagation, differentiation and migration capacities of abdominal ASCs that is explained by their increased tendency to over-accumulate reactive oxygen species (ROS) in culture. ROS over production in abdominal ASCs was shown to be controlled by the NADPH oxidase NOX1. The unique features of MSCs derived from different tissues suggest a tissue specific molecular signature arising from the tissue of origin that is retained during culture. The implications of this phenomenon on our understanding of the role and function of MSCs in situ as well as on their clinical utilization, is discussed

Stroma-cell dependent hematopoiesis

SCOPUS: ar.jinfo:eu-repo/semantics/publishe