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Bioactive materials interact with cells and modulate their characteristics which enable the generation of cell-based products with desired specifications. However, their evaluation and impact are often overlooked when establishing a cell therapy manufacturing process. In this study, we investigated the role of different surfaces for tissue culture including, untreated polystyrene surface, uncoated Cyclic Olefin Polymer (COP) and COP coated with collagen and recombinant fibronectin. It was observed that human mesenchymal stromal cells (hMSCs) expanded on COP-coated plates with different bioactive materials resulted in improved cell growth kinetics compared to traditional polystyrene plates and non-coated COP plates. The doubling time obtained was 2.78 and 3.02 days for hMSC seeded in COP plates coated with collagen type I and recombinant fibronectin respectively, and 4.64 days for cells plated in standard polystyrene treated plates. Metabolite analysis reinforced the findings of the growth kinetic studies, specifically that cells cultured on COP plates coated with collagen I and fibronectin exhibited improved growth as evidenced by a higher lactate production rate (9.38 × 105 and 9.67 × 105 pmol/cell/day, respectively) compared to cells from the polystyrene group (5.86 × 105 pmol/cell/day). This study demonstrated that COP is an effective alternative to polystyrene-treated plates when coated with bioactive materials such as collagen and fibronectin, however COP-treated plates without additional coatings were found not to be sufficient to support cell growth. These findings demonstrate the key role biomaterials play in the cell manufacturing process and the importance of optimising this selection.

Bioactive materials interact with cells and modulate their characteristics which enables the generation of cell-based products with desired specifications. However, their evaluation and impact are often overlooked when establishing a cell therapy manufacturing process. In this study, we investigated the role of different surfaces for tissue culture including, untreated polystyrene surface, uncoated Cyclic Olefin Polymer (COP) and COP coated with collagen and recombinant fibronectin. It was observed that hMSCs expanded on COP-coated plates with different bioactive materials resulted in improved cell growth kinetics compared to traditional polystyrene plates and uncoated COP non-coated plates. The doubling time obtained was 2.78 and 3.02 days for hMSC seeded in COP plates coated with collagen type I and recombinant fibronectin respectively, and 4.64 days for cells plated in standard polystyrene treated plates. Metabolite analysis reinforced the findings of the growth kinetic studies, specifically that cells cultured on COP plates coated with collagen I and fibronectin exhibited improved growth as evidenced by a higher lactate production rate (9.38x105 and 9.67x105 pmol.cell-1.day-1, respectively) compared to cells from the polystyrene group (5.86x105 pmol.cell-1.day-1). This study demonstrated that COP is an effective alternative to polystyrene-treated plates when coated with bioactive materials such as collagen and fibronectin, however COP-treated plates in isolation was found not to be sufficient to support cell growth. These findings demonstrate the key role biomaterials play in the cell manufacturing process and the importance of optimising this selection.

Aim: This is the first analysis of both clinical trials and published studies that employ umbilical cord mesenchymal stromal cells, for the decade 2007–2017. Materials & methods: Searching international databases, we found 178 registered trials and 98 publications. Results: Among the registered clinical trials, 20% have resulted in publications so far. Among the publications, 18% report safety and 74% report some form of improvement. Between 36 and 45% of the publications do not report aspects of the cell manufacturing, including isolation method, culture medium or number of culture passages. Conclusion: Analyses that link trials with publications can elucidate factors that promote study completion and publication. More full disclosure of cell manufacturing is needed to evaluate the efficacy of mesenchymal stromal cell isolated from umbilical cord tissue (UC-MSC) products.

The emergence of cell and gene therapies (CGTs) as a novel therapeutic modality has ushered in significant scope and opportunity to address previously unmet need. The rationale behind such therapies is to use cells, somatic, or modified/reprogrammed, to trigger regeneration of damaged tissues or targeting of cancer cells, for example. With increasing numbers of CGT products receiving regulatory approval, there is now a focus on establishing scalable and robust manufacturing processes for both autologous (patient-specific) and allogeneic (universal donor) which are both cost effective and can meet expected demand. One of the cell types under evaluation in numerous clinical trials is human mesenchymal stem/stromal cells (hMSCs) that possess both immunomodulatory properties and in vitro differentiation capability. These properties have been explored for conditions such as graft-versus host disease (GvHD), acute myocardial infarction (AMI), and Crohn’s disease among others. One of the current engineering challenges for hMSC-based products is to generate clinically relevant numbers of cells to meet the dose criteria while retaining the product’s critical quality attributes (CQAs). Traditional planar-based culture systems have several disadvantages such as low scalability, limited control and are highly dependent on human handling. Significant research and development activity has focused on establishing scalable and controlled bioprocesses for hMSC expansion that keep the cells’ biological properties. This chapter focuses on the discussion of the various options that manufacturers face during each stage of the hMSC from isolation, to expansion, downstream processing, and finally the product formulation.

The existence of private banks that provide family storage of cord blood and other perinatal cells has played a significant role in the advancement of clinical trials. Today, private storage of cord blood and cord tissue is offered in dozens of countries. The storage procedures used by private banks vary widely and need to be validated to ensure that clients can use their biological samples for emerging therapies. Over a thousand patients per year currently participate in advanced cell therapy trials with perinatal cells. A review of the first decade of regenerative medicine with perinatal cells shows there is growing use of these cells, but so far most of the research is taking place in only a handful of countries. A review of clinical trials that use all sources of mesenchymal stem/stromal cells (MSCs) for regenerative medicine indicates that there remain unexplored opportunities for perinatal MSCs.

Aim: The first review of advanced cell therapy trials with perinatal cells. Materials & methods: We compiled 281 clinical trials of advanced cell therapy with perinatal cells that were registered in 2005–2015. Results: The most common cell source in these trials is cord blood, but the cell type that provides the mechanism of action in the majority of trials is mesenchymal stem/stromal cells. We analyze trends among the 15 parameters we compiled for these trials. Conclusion: Advanced cell therapy with perinatal cells is a new field that covers a wide range of diagnoses but where most of the trials are early Phase. Researchers in different countries tend to work with a preferred cell source and cell type.