TY - JOUR
T1 - Concise Review
T2 - Mesenchymal Stem Cell-Based Drug Delivery: The Good, the Bad, the Ugly, and the Promise
AU - Krueger, Timothy E.G.
AU - Thorek, Daniel L.J.
AU - Denmeade, Samuel R.
AU - Isaacs, John T.
AU - Brennen, W. Nathaniel
N1 - Funding Information:
We acknowledge the expert assistance of Dr. Kenneth Valkenburg and Marie-France Penet for their help with IC and IV injections, respectively. This work was supported by the following sources: Prostate Cancer Foundation Young Investigator Award (W.N.B. and D.L.J.T.), Patrick C. Walsh Prostate Cancer Research Fund (W.N.B. and D.L.J.T.), SKCCC CCSG developmental funds [P30 CA006973, (W.N.B.)], NIH-Prostate SPORE [P50 CA058236, (S.R.D. and J.T.I.)], Department of Defense Prostate Cancer Research Program [W81XWH-16-1-0410, (J.T.I.) and W81XWH-17-1-0528, (W.N.B.)], and NCI [R01CA201035, (D.L.J.T.)].
Publisher Copyright:
© 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press
PY - 2018/9
Y1 - 2018/9
N2 - The development of mesenchymal stem cells (MSCs) as cell-based drug delivery vectors for numerous clinical indications, including cancer, has significant promise. However, a considerable challenge for effective translation of these approaches is the limited tumor tropism and broad biodistribution observed using conventional MSCs, which raises concerns for toxicity to nontarget peripheral tissues (i.e., the bad). Consequently, there are a variety of synthetic engineering platforms in active development to improve tumor-selective targeting via increased homing efficiency and/or specificity of drug activation, some of which are already being evaluated clinically (i.e., the good). Unfortunately, the lack of robust quantification and widespread adoption of standardized methodologies with high sensitivity and resolution has made accurate comparisons across studies difficult, which has significantly impeded progress (i.e., the ugly). Herein, we provide a concise review of active and passive MSC homing mechanisms and biodistribution postinfusion; in addition to in vivo cell tracking methodologies and strategies to enhance tumor targeting with a focus on MSC-based drug delivery strategies for cancer therapy. Stem Cells Translational Medicine 2018;1–13.
AB - The development of mesenchymal stem cells (MSCs) as cell-based drug delivery vectors for numerous clinical indications, including cancer, has significant promise. However, a considerable challenge for effective translation of these approaches is the limited tumor tropism and broad biodistribution observed using conventional MSCs, which raises concerns for toxicity to nontarget peripheral tissues (i.e., the bad). Consequently, there are a variety of synthetic engineering platforms in active development to improve tumor-selective targeting via increased homing efficiency and/or specificity of drug activation, some of which are already being evaluated clinically (i.e., the good). Unfortunately, the lack of robust quantification and widespread adoption of standardized methodologies with high sensitivity and resolution has made accurate comparisons across studies difficult, which has significantly impeded progress (i.e., the ugly). Herein, we provide a concise review of active and passive MSC homing mechanisms and biodistribution postinfusion; in addition to in vivo cell tracking methodologies and strategies to enhance tumor targeting with a focus on MSC-based drug delivery strategies for cancer therapy. Stem Cells Translational Medicine 2018;1–13.
KW - Cell size
KW - Cell-based therapy
KW - Drug delivery
KW - Homing
KW - In vivo cell tracking
KW - Mesenchymal stem cell
UR - http://www.scopus.com/inward/record.url?scp=85052838099&partnerID=8YFLogxK
U2 - 10.1002/sctm.18-0024
DO - 10.1002/sctm.18-0024
M3 - Review article
C2 - 30070053
AN - SCOPUS:85052838099
SN - 2157-6564
VL - 7
SP - 651
EP - 663
JO - Stem Cells Translational Medicine
JF - Stem Cells Translational Medicine
IS - 9
ER -