The concept of mesenchymal stem cells has gained wide popularity. Despite the rapid growth of the field, uncertainties remain with respect to the defining characteristics of these cells, including ...their potency and self-renewal. These uncertainties are reflected in a growing tendency to question the very use of the term. This commentary revisits the experimental origin of the concept of the population(s) referred to as mesenchymal stem cells and the experimental framework required to assess their stemness and function.
Mesenchymal stem cells (MSCs) are the focus of intensive efforts worldwide directed not only at elucidating their nature and unique properties but also developing cell-based therapies for a diverse ...range of diseases. More than three decades have passed since the original formulation of the concept, revolutionary at the time, that multiple connective tissues could emanate from a common progenitor or stem cell retained in the postnatal bone marrow. Despite the many important advances made since that time, substantial ambiguities still plague the field regarding the nature, identity, function, mode of isolation and experimental handling of MSCs. These uncertainties have a major impact on their envisioned therapeutic use.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Adipose stromal cells (ASCs) serve as mesenchymal progenitors in white adipose tissue (WAT). Intercellular interactions involving ASCs have remained obscure. By merging phage display technology with ...fluorescence-activated cell sorting (FACS), we screened a combinatorial library for peptides that target mouse ASCs in vivo. We isolated peptide CSWKYWFGEC that specifically homes to ASCs, used it as bait to purify the corresponding ASC surface receptor, and identified it as a previously unreported cleavage product of decorin (DCN) lacking the glycanation site (termed ΔDCN). We demonstrate that ΔDCN is differentially expressed on ASC surface. In a screen for ΔDCN-binding proteins, we identified resistin, an adipokine for which the receptor has been unknown. Expression of ΔDCN in 3T3-L1 cells promoted proliferation and migration but suppressed lipid accumulation upon adipogenesis induction, which was resistin dependent. We conclude that ΔDCN serves as a functional receptor of resistin in adipocyte progenitors and may regulate WAT expansion.
► Phage display identifies peptides that home to adipose stromal cells (ASCs) in vivo ► A nonglycanated isoform of decorin (ΔDCN) is isolated as a peptide target ► The adipokine resistin is identified as a ligand for ΔDCN on the ASC surface ► Resistin-ΔDCN interaction controls ASC proliferation, migration, and differentiation
...staff calling patients into clinical areas should go well into the waiting room and speak up clearly. ...offering assistive devices, which are poorly maintained with potentially flat or missing ...batteries and without instructions for the patient or staff, is pure wishful thinking.
The connection between obesity and accelerated cancer progression has been established, but the mediating mechanisms are not well understood. We have shown that stromal cells from white adipose ...tissue (WAT) cooperate with the endothelium to promote blood vessel formation through the secretion of soluble trophic factors. Here, we hypothesize that WAT directly mediates cancer progression by serving as a source of cells that migrate to tumors and promote neovascularization. To test this hypothesis, we have evaluated the recruitment of WAT-derived cells by tumors and the effect of their engraftment on tumor growth by integrating a transgenic mouse strain engineered for expansion of traceable cells with established allograft and xenograft cancer models. Our studies show that entry of adipose stromal and endothelial cells into systemic circulation leads to their homing to and engraftment into tumor stroma and vasculature, respectively. We show that recruitment of adipose stromal cells by tumors is sufficient to promote tumor growth. Finally, we show that migration of stromal and vascular progenitor cells from WAT grafts to tumors is also associated with acceleration of cancer progression. These results provide a biological insight for the clinical association between obesity and cancer, thus outlining potential avenues for preventive and therapeutic strategies.
Abstract Platelet-rich plasma (PRP) was prepared from human adult peripheral blood and from human umbilical cord (uc) blood and the properties were compared in a series of in vitro bioassays. ...Quantification of growth factors in PRP and platelet-poor plasma (PPP) fractions revealed increased levels of mitogenic growth factors PDGF-AB, PDGF-BB, and FGF-2, the angiogenic agent VEGF and the chemokine RANTES in ucPRP compared to adult PRP (aPRP) and PPP. To compare the ability of the various PRP products to stimulate proliferation of human bone marrow (BM), rat BM and compact bone (CB)-derived mesenchymal stem cells (MSC), cells were cultured in serum-free media for 4 and 7 days with varying concentrations of PRP, PPP, or combinations of recombinant mitogens. It was found that while all forms of PRP and PPP were more mitogenic than fetal bovine serum, ucPRP resulted in significantly higher proliferation by 7 days than adult PRP and PPP. We observed that addition of as little as 0.1% ucPRP caused greater proliferation of MSC effects than the most potent combination of recombinant growth factors tested, namely PDGF-AB + PDGF-BB + FGF-2, each at 10 ng/mL. Similarly, in chemotaxis assays, ucPRP showed greater potency than adult PRP, PPP from either source, or indeed than combinations of either recombinant growth factors (PDGF, FGF, and TGF-β1) or chemokines previously shown to stimulate chemotactic migration of MSC. Lastly, we successfully demonstrated that PRP and PPP represented a viable alternative to FBS containing media for the cryo-preservation of MSC from human and rat BM.
Along with scientific and regulatory issues, the translation of cell and tissue therapies in the routine clinical practice needs to address standardization and cost-effectiveness through the ...definition of suitable manufacturing paradigms.
Abstract We address the issue of the potential for malignant transformation of cultured mesenchymal stromal cells (MSC) commonly used in clinical cell-therapy protocols and describe the culture ...conditions under which tumorigenesis is likely to be an extremely uncommon event.
Although recent data suggests that osteoblasts play a key role within the hematopoietic stem cell (HSC) niche, the mechanisms underpinning this remain to be fully defined. The studies described ...herein examine the role in hematopoiesis of Osteopontin (Opn), a multidomain, phosphorylated glycoprotein, synthesized by osteoblasts, with well-described roles in cell adhesion, inflammatory responses, angiogenesis, and tumor metastasis. We demonstrate a previously unrecognized critical role for Opn in regulation of the physical location and proliferation of HSCs. Within marrow, Opn expression is restricted to the endosteal bone surface and contributes to HSC transmarrow migration toward the endosteal region, as demonstrated by the markedly aberrant distribution of HSCs in Opn–/– mice after transplantation. Primitive hematopoietic cells demonstrate specific adhesion to Opn in vitro via β1 integrin. Furthermore, exogenous Opn potently suppresses the proliferation of primitive HPCs in vitro, the physiologic relevance of which is demonstrated by the markedly enhanced cycling of HSC in Opn–/– mice. These data therefore provide strong evidence that Opn is an important component of the HSC niche which participates in HSC location and as a physiologic-negative regulator of HSC proliferation.
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