Therapeutic potential of intravenously administered human mesenchymal stromal cells

2011 ◽  
Vol 31 (04) ◽  
pp. 269-274 ◽  
Author(s):  
K. Kollar ◽  
E. Seifried ◽  
R. Henschler
Keyword(s):  
Stromal Cells ◽  
Progenitor Cell ◽  
Therapeutic Potential ◽  
Culture Conditions ◽  
Human Mesenchymal Stromal Cells ◽  
Progenitor Cell Population ◽  
Multipotent Progenitors ◽  
Number Of Factors ◽  
Tissue Recovery ◽  
Preclinical And Clinical Studies

SummaryMesenchymal stem cells (MSC) represent a stem and progenitor cell population that has been shown to promote tissue recovery in preclinical and clinical studies. The study of MSC migration following systemic infusion of exogenous MSC is difficult. The challenges facing these efforts are due to a number of factors, including defining culture conditions for MSC, the phenotype of cultured MSC, the differences observed between cultured MSC and freshly isolated MSC. However, even if, MSC populations consist of a mixture of stem and more committed multipotent progenitors, it remains probable that these cell populations are still useful in the clinic as discussed in this review.

scholarly journals Development of thymic NK cells from double negative 1 thymocyte precursors

Blood ◽  
2011 ◽  
Vol 118 (13) ◽  
pp. 3570-3578 ◽  
Author(s):  
Claudia L. Vargas ◽  
Jennifer Poursine-Laurent ◽  
Liping Yang ◽  
Wayne M. Yokoyama
Keyword(s):  
Bone Marrow ◽  
Nk Cells ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Progenitor Cell ◽  
Nk Cell ◽  
Double Negative ◽  
Progenitor Cell Population ◽  
Intrathymic Injection

Abstract The differentiation of natural killer (NK) cells and a subpopulation of NK cells which requires an intact thymus, that is, thymic NK cells, is poorly understood. Previous in vitro studies indicate that double negative (CD4−CD8−, DN) thymocytes can develop into cells with NK cell markers, but these cells have not been well characterized. Herein, we generated and characterized NK cells differentiating from thymic DN precursors. Sorted DN1 (CD44+CD25−) CD122−NK1.1− thymocytes from Rag1−/− mice were adoptively transferred into Rag1−/−Ly5.1 congenic mice. After intrathymic injection, donor-derived cells phenotypically resembling thymic NK cells were found. To further study their differentiation, we seeded sorted DN1 CD122−NK1.1− thymocytes on irradiated OP9 bone marrow stromal cells with IL-15, IL-7, Flt3L, and stem cell factor. NK1.1+ cells emerged after 7 days. In vitro differentiated NK cells acquired markers associated with immature bone marrow–derived NK cells, but also expressed CD127, which is typically found on thymic NK cells. Furthermore, we found that in vitro cells generated from thymic precursors secreted cytokines when stimulated and degranulated on target exposure. Together, these data indicate that functional thymic NK cells can develop from a DN1 progenitor cell population.

Cell behavior of human mesenchymal stromal cells in response to silica/collagen based xerogels and calcium deficient culture conditions

2017 ◽  
Vol 12 (4) ◽  
pp. 045003 ◽  
Author(s):  
Alena-Svenja Wagner ◽  
Kristina Glenske ◽  
Anja Henß ◽  
Benjamin Kruppke ◽  
Sina Rößler ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Culture Conditions ◽  
Cell Behavior ◽  
Human Mesenchymal Stromal Cells

scholarly journals Preconditioning of Rat Bone Marrow-Derived Mesenchymal Stromal Cells with Toll-Like Receptor Agonists

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Fabiana Evaristo-Mendonça ◽  
Gabriela Sardella-Silva ◽  
Tais Hanae Kasai-Brunswick ◽  
Raquel Maria Pereira Campos ◽  
Pablo Domizi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Culture Conditions ◽  
Poly I:C ◽  
Dependent Manner ◽  
Toll Like Receptor ◽  
Preclinical Research ◽  
Polycytidylic Acid

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are dynamic cells that can sense the environment, adapting their regulatory functions to different conditions. Accordingly, the therapeutic potential of BM-MSCs can be modulated by preconditioning strategies aimed at modifying their paracrine action. Although rat BM-MSCs (rBM-MSCs) have been widely tested in preclinical research, most preconditioning studies have employed human and mouse BM-MSCs. Herein, we investigated whether rBM-MSCs modify their phenotype and paracrine functions in response to Toll-like receptor (TLR) agonists. The data showed that rBM-MSCs expressed TLR3, TLR4, and MDA5 mRNA and were able to internalize polyinosinic-polycytidylic acid (Poly(I:C)), a TLR3/MDA5 agonist. rBM-MSCs were then stimulated with Poly(I:C) or with lipopolysaccharide (LPS, a TLR4 agonist) for 1 h and were grown under normal culture conditions. LPS or Poly(I:C) stimulation did not affect the viability or the morphology of rBM-MSCs and did not modify the expression pattern of key cell surface markers. Poly(I:C) did not induce statistically significant changes in the release of several inflammatory mediators and VEGF by rBM-MSCs, although it tended to increase IL-6 and MCP-1 secretion, whereas LPS increased the release of IL-6, MCP-1, and VEGF, three factors that were constitutively secreted by unstimulated cells. The neurotrophic activity of the conditioned medium from unstimulated and LPS-preconditioned rBM-MSCs was investigated using dorsal root ganglion explants, showing that soluble factors produced by unstimulated and LPS-preconditioned rBM-MSCs can stimulate neurite outgrowth similarly, in a VEGF-dependent manner. LPS-preconditioned cells, however, were slightly more efficient in increasing the number of regrowing axons in a model of sciatic nerve transection in rats. In conclusion, LPS preconditioning boosted the production of constitutively secreted factors by rBM-MSCs, without changing their mesenchymal identity, an effect that requires further investigation in exploratory preclinical studies.

Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation

Blood ◽  
2010 ◽  
Vol 115 (8) ◽  
pp. 1549-1553 ◽  
Author(s):  
Karin Tarte ◽  
Julien Gaillard ◽  
Jean-Jacques Lataillade ◽  
Loic Fouillard ◽  
Martine Becker ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Calf Serum ◽  
Human Leukocyte ◽  
Culture Conditions ◽  
Human Mscs ◽  
Clinical Grade ◽  
Human Mesenchymal Stromal Cells

Abstract Clinical-grade human mesenchymal stromal cells (MSCs) have been expanded in vitro for tissue engineering or immunoregulatory purposes without standardized culture conditions or release criteria. Although human MSCs show poor susceptibility for oncogenic transformation, 2 recent studies described their capacity to accumulate chromosomal instability and to give rise to carcinoma in immunocompromised mice after long-term culture. We thus investigated the immunologic and genetic features of MSCs expanded with fetal calf serum and fibroblast growth factor or with platelet lysate in 4 cell-therapy facilities during 2 multicenter clinical trials. Cultured MSCs showed a moderate expression of human leukocyte antigen-DR without alteration of their low immunogenicity or their immunomodulatory capacity. Moreover, some transient and donor-dependent recurring aneuploidy was detected in vitro, independently of the culture process. However, MSCs with or without chromosomal alterations showed progressive growth arrest and entered senescence without evidence of transformation either in vitro or in vivo.

Sign in / Sign up

Export Citation Format

Share Document