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

被引:43
|
作者
Brooks, Anastasia [1 ,3 ]
Futrega, Kathryn [4 ]
Liang, Xiaowen [1 ]
Hu, Xiaoling [1 ]
Liu, Xin [1 ]
Crawford, Darrell H. G. [5 ]
Doran, Michael R. [2 ,4 ,6 ]
Roberts, Michael S. [1 ,7 ]
Wang, Haolu [1 ,8 ]
机构
[1] Univ Queensland, Therapeut Res Ctr, Diamantina Inst, Brisbane, Qld 4103, Australia
[2] Univ Queensland, Translat Res Inst, Mater Res Inst, Brisbane, Qld, Australia
[3] Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia
[4] Queensland Univ Technol, Translat Res Inst, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia
[5] Univ Queensland, Greenslopes Private Hosp, Gallipoli Med Res Inst, Sch Clin Med, Brisbane, Qld, Australia
[6] Australian Natl Univ, Australian Natl Ctr Publ Awareness Sci, Canberra, ACT, Australia
[7] Univ South Australia, Basil Hetzel Inst, Sch Pharm & Med Sci, Adelaide, SA, Australia
[8] Shanghai Jiao Tong Univ, Ren Ji Hosp, Sch Med, Dept Biliary Pancreat Surg, Shanghai, Peoples R China
基金
英国医学研究理事会;
关键词
Stem cells; Quantitative detection; Modeling; Kinetics; MARROW MONONUCLEAR-CELLS; BLOOD STEM-CELLS; BONE-MARROW; STROMAL CELLS; PROGENITOR CELLS; ISCHEMIC-STROKE; GENE-THERAPY; BIODISTRIBUTION; EFFICACY; TRACKING;
D O I
10.1002/sctm.17-0209
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:78 / 86
页数:9
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