Mesenchymal stem or stromal cells: a review of clinical applications and manufacturing practices

Abstract

Mesenchymal stem cells (MSCs) have recently generated great interest in the fields of regenerative medicine and immunotherapy due to their unique biologic properties. In this review we attempt to provide an overview of the current clinical status of MSC therapy, primarily focusing on immunomodulatory and regenerative or tissue repair applications of MSCs. In addition, current manufacturing is reviewed with attention to variation in practices (e.g., starting material, approach to culture and product testing). There is considerable variation among the 218 clinical trials assessed here; variations include proposed mechanisms of action, optimal dosing strategy, and route of administration. To ensure the greatest likelihood of success in clinical trials as the field progresses, attention must be given to the optimization of MSC culture.

Morphological features of IFN-γ–stimulated mesenchymal stromal cells predict overall immunosuppressive capacity

“…A major contributor to these inconsistent clinical outcomes may be the inherent variability in the immunosuppressive capacity of MSC lines due to differing tissues of origin, manufacturing processes, and donor-specific differences (10,(21)(22)(23). Although this functional heterogeneity is well known, no reliable predictors of MSC immunosuppressive capacity have been identified (3,24). Another significant challenge facing development of MSC-based therapies is the lack of well-defined, robust assays for assessing their immunosuppressive function.…”

“…A major challenge in the development of consistently effective MSC-based immunosuppressive therapies is that MSC lines derived from different donors and manufacturing processes (i.e., cell expansion) can possess markedly dissimilar immunosuppressive function (3,5,6). Although methods exist to assess MSC immunosuppression in vitro, they are often based on only a few measured outcomes, assay culture conditions, and donor MSC samples (5, 7-9).…”

“…immunosuppression | mesenchymal stromal cells | morphology | high-content imaging | interferon-gamma H uman mesenchymal stromal cells (MSCs) can potently suppress immune responses in vitro and in animal models of human disease (1,2), but to date MSC-based therapies have produced mixed results in clinical trials for treatment of inflammatory and autoimmune diseases (3,4). A major challenge in the development of consistently effective MSC-based immunosuppressive therapies is that MSC lines derived from different donors and manufacturing processes (i.e., cell expansion) can possess markedly dissimilar immunosuppressive function (3,5,6).…”

A novel strategy to achieve effective drug delivery: exploit cells as carrier combined with nanoparticles

“…In fact, leukocytes and stem cells have been used for tumor immunotherapy and tissue regeneration in clinical trials (Sharma et al, 2014;Behfar et al, 2014;Firor et al, 2015;Ikeda & Shiku, 2015). In recent decades, surprising results were developed by exploiting cells as vehicles combined with nanodrugs for therapy.…”

Optimization of the Wound Scratch Assay to Detect Changes in Murine Mesenchymal Stromal Cell Migration After Damage by Soluble Cigarette Smoke Extract

“…An understanding of cell migration is particularly relevant to emerging therapies used to repair damaged tissues and treat pathological conditions, including cell transplantation technologies and artificial tissue grafting 2 . Given the current interest in the role of mesenchymal stromal cells (MSCs) in mediating tissue repair 3 , quantifying the migratory capacity of these cells using an assay that is rigorously quantifiable, adaptable, and cost-effective is of interest. Importantly, such an assay must be sufficiently sensitive to detect relatively subtle changes in cellular migratory capacity after damage.…”