Concise Review: Quantitative Detection and Modeling the In Vivo Kinetics of Therapeutic Mesenchymal Stem/Stromal Cells

Author:

Brooks Anastasia12,Futrega Kathryn3,Liang Xiaowen1,Hu Xiaoling1,Liu Xin1,Crawford Darrell H. G.4,Doran Michael R.356,Roberts Michael S.17,Wang Haolu18

Affiliation:

1. a Therapeutics Research Centre, The University of Queensland Diamantina Institute, Brisbane, Australia

2. b School of Biomedical Sciences The University of Queensland, Brisbane, Australia

3. c Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Brisbane, Australia

4. d School of Clinical Medicine The University of Queensland, Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Australia

5. e Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Australia

6. f Australian National Centre for the Public Awareness of Science, Australian National University, Canberra, Australia

7. g School of Pharmacy and Medical Sciences University of South Australia, Basil Hetzel Institute, Adelaide, Australia

8. h Department of Biliary-Pancreatic Surgery Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China

Abstract

Abstract Mesenchymal stem/stromal cells (MSCs) present a promising tool in cell-based therapy for treatment of various diseases. Currently, optimization of treatment protocols in clinical studies is complicated by the variations in cell dosing, diverse methods used to deliver MSCs, and the variety of methods used for tracking MSCs in vivo. Most studies use a dose escalation approach, and attempt to correlate efficacy with total cell dose. Optimization could be accelerated through specific understanding of MSC distribution in vivo, long-term viability, as well as their biological fate. While it is not possible to quantitatively detect MSCs in most targeted organs over long time periods after systemic administration in clinical trials, it is increasingly possible to apply pharmacokinetic modeling to predict their distribution and persistence. This Review outlines current understanding of the in vivo kinetics of exogenously administered MSCs, provides a critical analysis of the methods used for quantitative MSC detection in these studies, and discusses the application of pharmacokinetic modeling to these data. Finally, we provide insights on and perspectives for future development of effective therapeutic strategies using pharmacokinetic modeling to maximize MSC therapy and minimize potential side effects.

Funder

National Health and Medical Research Council

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,General Medicine

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