Convergence of Cell Pharmacology and Drug Delivery

Abstract

Summary Cellular therapy is enabling new approaches to tackle significant unmet needs in areas such as regenerative medicine and immunotherapy. The pharmacology of cell therapeutics becomes of critical importance to assure that these new drugs work reproducibly and effectively. Cell pharmacology can benefit from adapting principles of classical molecular drug pharmacokinetics (PK) and pharmacodynamics (PD) to quantitatively understand rate‐limiting constraints of cell fate after administration. Future innovations focused on improvements in drug delivery using a PK/PD perspective can aid in designing a cell therapeutic product to overcome any pharmacological barriers for a given disease application. Herein, we present a perspective on the development of an ex vivo mesenchymal stromal therapeutic using a PK/PD framework and also present examples of general cell engineering techniques that implicitly influence the PK/PD curve by genetically modifying cells to regulate their in vivo duration, biodistribution, and activity. stem cells translational medicine 2019;8:874&879

Persistency of Mesenchymal Stromal/Stem Cells in Lungs

“…Since the initial idea of engraftment and differentiation has been largely abandoned and substituted with MSC immunomodulatory and paracrine actions, basic knowledge such as time of persistency of MSCs into the lung following systemic or local administration is still debated. This issue has strong implications in terms of pharmacokinetics and pharmacodynamics for MSCs with relevant therapeutic impact on their regenerative potential (Brooks et al, 2018;Aijaz et al, 2019;Salvadori et al, 2019). The data presented in this paper corroborate the MSC activity through their secretome in relation to their lung persistency.…”

Mesenchymal Stromal Cell Therapeutic Delivery: Translational Challenges to Clinical Application

“…In 2006, the International Society for Cellular Therapy (ISCT) published their first position statement on defining minimal criteria for MSCs (9), followed by several updates mainly focusing on the refinement of standards for therapeutic efficacy (10–12). Efforts to further refine cell pharmacology and drug delivery are ongoing (13). Thus, it becomes apparent that MSC research has undergone numerous advancements over time, in order to understand and benefit from the interesting properties of these cells.…”

Advancements in Assessments of Bio-Tissue Engineering and Viable Cell Delivery Matrices Using Bile Acid-Based Pharmacological Biotechnologies

“…A feasible viable cell delivery system must first meet several essential requirements; particularly, that it must be a stable and reproducible system with optimal characteristics for in vivo applications and potential large scale pharmaceutical manufacturing [ 60 , 61 , 62 , 63 ].…”

“…Microencapsulated pancreatic islets and insulinoma cell lines can be cultured using traditional media such as Roswell Park Memorial Institute (RMPI) 1640, Connaught Medical Research Laboratories (CMRL) 1066 and Dulbecco’s Modified Eagle’s Medium (DMEM), making them more versatile [ 5 , 63 , 74 , 75 ]. From these aforementioned media, CMRL has been found to be effective for culturing islets in vitro, although developments continue to be made to find more optimal media combinations [ 76 , 77 , 78 ].…”