Translating Research into Clinical Scale Manufacturing of Mesenchymal Stromal Cells

Abstract

It sounds simple to obtain sufficient numbers of cells derived from fetal or adult human tissues, isolate and/or expand the stem cells, and then transplant an appropriate number of these cells into the patient at the correct location. However, translating basic research into routine therapies is a complex multistep process which necessitates product regulation. The challenge relates to managing the expected therapeutic benefits with the potential risks and to balance the fast move to clinical trials with time-consuming cautious risk assessment. This paper will focus on the definition of mesenchymal stromal cells (MSCs), and challenges and achievements in the manufacturing process enabling their use in clinical studies. It will allude to different cellular sources, special capacities of MSCs, but also to current regulations, with a special focus on accessory material of human or animal origin, like media supplements. As cellular integrity and purity, formulation and lot release testing of the final product, validation of all procedures, and quality assurance are of utmost necessity, these topics will be addressed.

In vitro Differentiation of Adipose-Derived Mesenchymal Stem Cell into Insulin-Producing Cells

“…Bieback et al, reported that the culture conditions could enhance or change properties of MSC if protocols are not standardized. Classical basal culturing media for MSC consists of DMEM or α-MEM supplemented with 10% to 20% of fetal bovine serum [11]. Another study reported that when cells were grown in Dulbecco's modified Eagle's medium (DMEM) the isolated ADSC, expanded easily, developed a fibroblast-like morphology and their differentiation capability were more effective [12].…”

The Potential Impact of Bone Tissue Engineering in the Clinic

“…Bone tissue in the clinic Review others), angiogenic (PDGF, VEGF, among others), inflammation-control (TNFα, interleukins, interferon-γ, among others) and systemic factors (Vitamin D, growth hormone, calcitonin, parathyroid hormone, among others) [44][45][46][47]. These cell signaling molecules have been studied extensively in the laboratory but few have been used in therapies that have gone through clinical trials.…”

Towards Clinical Application of Mesenchymal Stromal Cells: Perspectives and Requirements for Orthopaedic Applications

“…However, translating basic research into clinical application is a complex multistep process (Bieback, Karagianni et al 2011). It necessitates product regulation by the regulatory authorities and accurate management of the expected therapeutic benefits with the potential risks in order to balance the speed of clinical trials with a time-consuming, cautious risk assessment (Sensebe, Bourin et al 2011).…”

“…It is obvious that MSC need to be further characterised in clinical studies with standardized protocols (Bieback, Karagianni et al 2011;Sensebe, Bourin et al 2011). Furthermore, despite immense work, still MSC cannot be identified as a distinct cell population by a set of marker proteins as CD34 defines hematopoietic stem cells.…”