Use Of Mesenchymal Stem Cells In Therapy Research Articles

The immunomodulatory function of mesenchymal stem cells: mode of action and pathways.

Mesenchymal stem cells (MSCs) are being increasingly investigated as a therapeutic alternative, not only for their possible regenerative potential but also for their immunomodulatory action, which is being exploited for controlling diseases associated with inflammation. Understanding their direct and indirect target cells, as well as their mode of action and relevant pathways, is a prerequisite for the appropriate and optimal use of MSCs in therapy. Here, we review recent findings on the effects of MSCs on adaptive and innate immune cells. We also consider the impact of the environment on MSC profile, both anti- and proinflammatory, and the mechanisms and molecular pathways through which their effects are mediated, both at the MSC and target cell levels.

Adult Stem Cell Therapy in Chronic Liver Diseases

The transplantation of mesenchymal stem cells (MSCs) represents a potentially effective therapy for chronic liver diseases. The potential of MSCs in the treatment of chronic liver disease is based on their ability to differentiate into multiple cell types including hepatocytes, their immunosuppressive properties, and their ability to secrete various trophic factors. This potential has been investigated in clinical and pre-clinical studies. Although the therapeutic mechanisms of MSC transplantation are still not fully characterized, accumulating evidence has revealed that various trophic factors secreted by MSCs play key therapeutic roles in regeneration. These trophic factors not only reduce inflammation, apoptosis, and fibrosis in damaged tissues but also stimulate angiogenesis and tissue regeneration in the impaired liver. In this review, we summarize the basic and therapeutic properties of MSCs, their therapeutic mechanisms of action, and potential transplantation routes for the treatment of chronic liver disease. We also discuss several risks associated with the use of MSCs in therapy, such as their fibrogenic potential and capacity to promote pre-existing tumor cell growth.

Serum‐free spheroid suspension culture maintains mesenchymal stem cell proliferation and differentiation potential

There have been many clinical trials recently using ex vivo-expanded human mesenchymal stem cells (MSCs) to treat several disease states such as graft-versus-host disease, acute myocardial infarction, Crohn's disease, and multiple sclerosis. The use of MSCs for therapy is expected to become more prevalent as clinical progress is demonstrated. However, the conventional 2-dimensional (2D) culture of MSCs is laborious and limited in scale potential. The large dosage requirement for many of the MSC-based indications further exacerbates this manufacturing challenge. In contrast, expanding MSCs as spheroids does not require a cell attachment surface and is amenable to large-scale suspension cell culture techniques, such as stirred-tank bioreactors. In the present study, we developed and optimized serum-free media for culturing MSC spheroids. We used Design of Experiment (DoE)-based strategies to systematically evaluate media mixtures and a panel of different components for effects on cell proliferation. The optimization yielded two prototype serum-free media that enabled MSCs to form aggregates and proliferate in both static and dynamic cultures. MSCs from spheroid cultures exhibited the expected immunophenotype (CD73, CD90, and CD105) and demonstrated similar or enhanced differentiation potential toward all three lineages (osteogenic, chondrogenic, adipogenic) as compared with serum-containing adherent MSC cultures. Our results suggest that serum-free media for MSC spheroids may pave the way for scale-up production of MSCs in clinically relevant manufacturing platforms such as stirred tank bioreactors.

Human mesenchymal stem cells in the treatment of neurological diseases.

Here we provide a comprehensive data on the unique features of mesenchymal stem cells (MSCs) which makes them feasible and preferred candidate for cell-based therapy in neurological clinic. From this point of view the most important features of these cells are: (1) availability from autologous sources independently from age of patient; (2) extensive expansion in vitro; (3) immunomodulatory "bystander" function after transplantation in vivo; (4) potentiality to protect, repair or eventually replace impaired or dysfunctional host cells. For complete this last task of functional regeneration of central nervous system, we have to take advantages of MSCs capability for transient, time-locked proliferation, migration to site of injury and their commitment to neuronal differentiation. However, if we are to make progress in the use of MSCs for therapy in the clinic it will be necessary to establish more unified, advanced standards for cells processing in vitro as well as safer and improved procedures for their delivery in vivo.

Human Stromal (Mesenchymal) Stem Cells: Basic Biology and Current Clinical Use for Tissue Regeneration

Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self-renewal and multi-lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts, adipocytes, chondrocytes and possibly other cell types including hepatocytes and astrocytes. Due to their ease of culture and multipotentiality, hMSC are increasingly employed as a source for cells suitable for a number of clinical applications, e.g., non-healing bone fractures and defects and also non-skeletal degenerative diseases like heart failure. Currently, the numbers of clinical trials that employ MSC are increasing. However, several biological and biotechnological challenges need to be overcome to benefit from the full potential of hMSC. In this current review, we present some of the most important and recent advances in understanding of the biology of hMSC and their current and potential use in therapy.