Mesenchymal stem or stromal cells (MSC) are considered a promising new therapeutic strategy for the treatment of several pathological conditions. Due to their immunomodulatory properties, they are currently employed in clinical trials aimed at preventing or treating steroid-resistant acute graft-versus-host disease (GvHD), a frequent complication of allogeneic hematopoietic stem cell transplantation (HSCT). In addition, the use of MSC has been proposed for the treatment of autoimmune diseases. A number of recent studies have focused on the influence of MSC on dendritic cell (DC) function. DCs play a critical role in initiating and regulating immune responses by promoting antigen-specific T cell activation. Moreover, they are involved in efficient cross-talk with different cells of the innate immune system. DC are the most effective antigen-presenting cells and prime naïve T cells to initiate adaptive immune responses including those against allogeneic cells or self-antigens. Thus, alteration of DC generation or function may greatly contribute to the inhibition of T cell responses. In this context, MSC were shown to interfere with DC maturation from monocytes or CD34(+) hemopoietic precursors thus further confirming their role in immune regulation and their usefulness in cell-based therapies.
[Show abstract][Hide abstract] ABSTRACT: Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.
[Show abstract][Hide abstract] ABSTRACT: Stem cell therapy is a potential method for the treatment of numerous diseases. The most frequent cellular source is bone marrow-derived mesenchymal stromal cells (BM-MSC). Human adipose-derived stromal cells (ADSC) share similar properties with BM-MSC as they support hematopoiesis, modulate ongoing immune responses and differentiate into cells of mesodermal origin. On the other hand, ADSC have higher frequency in situ, higher availability and very few ethical issues compared to BM-MSC giving them an advantage over BM-MSC for clinical use. Most of the methods used to isolate ADSC contain a collagenase digestion step, but the type of collagenase and time of sample digestion vary among studies and these differences could have an impact on the cell properties and thus in result comparison. To overcome this obstacle, we propose a new method to isolate ADSC from lipoaspirate without collagenase digestion step. We compared ADSC obtained with our method versus classical protocol using collagenase digestion. Cells obtained with our method are equivalent but has a better long term hematopoietic support than those obtained with classical method. Moreover, our method has an advantage over the classical one as it is easier, safer, faster, less expensive and more consistent with good manufacturing practices (GMP) to obtain large number of ADSC ex vivo.
Stem cells and development 05/2014; 23(19). DOI:10.1089/scd.2014.0071 · 3.73 Impact Factor
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