Delivery Of Cell-based Therapies Research Articles

Long Term Follow Up of the CAR T Recipient

AbstractT-cell therapy has emerged as transformative therapy for blood cancers. Autologous and allogeneic T-cells that have been genetically modified to express a chimeric antigen receptor, or CAR, have been shown to induce long-term remissions in patients with B-cell lymphoma, B-cell leukemia, and multiple myeloma. The delivery of cell-based therapies, whether autologous or allogeneic, is complex and requires collection, processing, and tracking systems that result in significant challenges to patients, their doctors, and the healthcare system. We will discuss the current clinical status of CAR T-cell therapies and important factors for physicians to consider in the long-term follow up of patients who have received any form of CAR T-cell or engineered T-cell therapy.

Application of Internet of Things in Cell-Based Therapy Delivery: Protocol for a Systematic Review.

BackgroundInternet of Things (IoT), or Industry 4.0, represents a smart shift to more interconnected manufacturing processes where individual entities within the supply chain communicate with each other to achieve greater flexibility and responsiveness in general manufacturing and leaner manufacturing to reduce the cost of production. IoT has become instrumental in driving leaner manufacturing and more efficient systems in other industries such as transportation and logistics. Cell-based therapeutic products could potentially transform various diseases; however, the delivery of these products is complex and challenging.ObjectiveThis study aims to understand the applicability of IoT in cell-based product supply chains and delivery.MethodsWe will search Medline, EMBASE (OvidSP), Web of Science, Cochrane Library & HEED, Scopus, ACM digital library, INSPEC, ScienceDirect, and the IEEE Xplore Digital Library for studies published after 2008 using a combination of keywords and subject headings related to IoT used in cell therapies. Additionally, a Google search to identify gray literature will be conducted. Two authors will independently screen the titles and abstracts identified from the search and accept or reject the studies according to the study inclusion criteria. Any discrepancies will then be discussed and resolved. The quality of the selected literature will be assessed using the Critical Appraisal Skills Programme systematic review checklist.ResultsData from eligible publications will be abstracted into a predesigned form to map the current and future directions of the technologies, applications, benefits, and challenges in the implementation of IoT in regenerative medicine. This study will be published in a peer-reviewed journal in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This systematic review will be executed by June 2020, and the completed review will be published in a peer-reviewed journal to inform future developments in IoT application for the delivery of cell-based therapies.ConclusionsThis review paper will provide an overview of all technologies available in the area and inspect the current IoT applications in cell-based therapies to identify the benefits, challenges, and future directions of using IoT to allow safe and cost-effective delivery of cell-based therapies.International Registered Report Identifier (IRRID)PRR1-10.2196/16935

Ventricular tachycardia: mechanistic insights derived from adenosine.

A foundational concept in cardiac electrophysiology is that understanding the cellular mechanism of an arrhythmia provides essential insight for developing targeted therapeutic options. However, current clinical understanding of arrhythmogenic mechanisms other than re-entry is rudimentary, and the means by which to diagnose and differentiate these mechanisms are poorly defined. Grouping these mechanistic subtypes into broad and nonspecific categories, for example, non–re-entry or focal, further underscores our incomplete understanding of these arrhythmias. As the field of cardiac electrophysiology, like the rest of medicine, evolves toward the delivery of cell-based therapies, the need for a deeper understanding of clinical arrhythmia mechanisms and their arrhythmogenic cell lineages is apparent. One major difference between re-entrant and non– re-entrant ventricular tachycardia (VT) is that the electrophysiological substrate for re-entry is acquired during postnatal development and is due to anatomic insult (eg, ischemic heart disease or viral myocarditis), whereas the substrate for triggered activity is likely often acquired during embryological development, occurring independent of anatomic injury or structural heart disease.1,2 These dichotomous electrophysiological substrates, re-entry and non–re-entry, require tailored approaches to confirm diagnosis. In this review, we will elaborate on the development of a methodological approach for diagnosing non–re-entrant VT, which centers on the unique mechanism-specific properties of adenosine. This approach differs substantively from standard laboratory pacing methodologies used to validate the diagnosis of re-entrant arrhythmias and which are founded on the principles of entrainment.3 Adenosine is an endogenous nucleoside that exercises multiple regulatory functions that affect impulse generation and conduction, autonomic function, contractility, coronary vasodilation, and O2 supply–demand balance.4 Adenosine is rapidly inactivated as it is taken up by the cell through simple diffusion or a nucleoside transport system and is then deaminated to inosine or phosphorylated to adenosine monophosphate.5 The plasma half-life of adenosine is <1.5 s. …

Regulatory Considerations for Manufacturing and Delivery of Cell-based Therapies for Cardiovascular Indications

Developers of cell-based therapies intended for the treatment of cardiovascular indications must address a number of regulatory issues related to the manufacturing and delivery of living cell products to patients. This article highlights issues that must be considered regarding the cell and tissue source and ancillary materials, the development of a regulatory acceptable manufacturing process, the importance of product characterization as a measure of product quality and clinical site logistics for handling and storing living cell products. Finally, regulatory issues regarding the various delivery systems commonly used for delivery cells to cardiac tissues are touched upon.