Modulating endothelial adhesion and migration impacts stem cell therapies efficacy

被引：19

作者：

Schaefer, Richard ^{[1
,2
]}

Schwab, Matthias ^{[3
,4
,19
,20
,21
,22
]}

Siegel, Georg ^{[2
]}

von Ameln-Mayerhofer, Andreas ^{[5
]}

Buadze, Marine ^{[3
]}

Lourhmati, Ali ^{[3
]}

Wendel, Hans-Peter ^{[6
,7
,8
]}

Kluba, Torsten ^{[9
]}

Krueger, Marcel A. ^{[10
]}

Calaminus, Carsten ^{[10
]}

Scheer, Eva ^{[2
]}

Dominici, Massimo ^{[11
]}

Grisendi, Giulia ^{[11
]}

Doeppner, Thorsten R. ^{[12
,13
]}

Schlechter, Jana ^{[12
]}

Finzel, Anne Kathrin ^{[3
]}

Gross, Dominic ^{[3
]}

Klaffschenkel, Roland ^{[2
]}

Gehring, Frank K. ^{[2
,14
]}

Spohn, Gabriele ^{[1
]}

Kretschmer, Anja ^{[1
]}

Bieback, Karen ^{[15
]}

Kraemer-Albers, Eva-Maria ^{[16
]}

Barth, Kerstin ^{[16
]}

Eckert, Anne ^{[17
]}

Elser, Stefanie ^{[18
]}

Schmehl, Joerg ^{[18
]}

Claussen, Claus D. ^{[18
]}

Seifried, Erhard ^{[1
]}

Hermann, Dirk M. ^{[12
]}

Northoff, Hinnak ^{[2
]}

Danielyan, Lusine ^{[3
,19
]}

机构：

[1] Goethe Univ Hosp, German Red Cross Blood Donor Serv Baden Wurttembe, Inst Transfus Med & Immunohematol, Frankfurt, Germany

[2] Univ Hosp Tubingen, Inst Clin & Expt Transfus Med, Tubingen, Germany

[3] Univ Hosp Tubingen, Dept Clin Pharmacol, Morgenstelle 8, D-72076 Tubingen, Germany

[4] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany

[5] Univ Tubingen, Sindelfingen Boblingen Med Ctr, Dept Pharm, Sindelfingen, Germany

[6] Univ Hosp Tubingen, Dept Thorac Surg, Tubingen, Germany

[7] Univ Hosp Tubingen, Dept Cardiac Surg, Tubingen, Germany

[8] Univ Hosp Tubingen, Dept Vasc Surg, Tubingen, Germany

[9] Univ Hosp Tubingen, Dept Orthopaed Surg, Tubingen, Germany

[10] Univ Hosp Tubingen, Dept Preclin Imaging & Radiopharm, Werner Siemens Imaging Ctr, Tubingen, Germany

[11] Univ Hosp Modena & Reggio Emilia, Dept Med & Surg Sci Children & Adults, Modena, Italy

[12] Univ Duisburg Essen, Dept Neurol, Essen, Germany

[13] Univ Med Ctr Gottingen, Dept Neurol, Gottingen, Germany

[14] 3T GmbH & Co KG, Tuttlingen, Germany

[15] Heidelberg Univ, Inst Transfus Med & Immunol, Med Fac Mannheim, German Red Cross Blood Serv Baden Wurttemberg Hes, Heidelberg, Germany

[16] Johannes Gutenberg Univ Mainz, Inst Dev Biol & Neurobiol, Mainz, Germany

[17] Univ Basel, Neurobiol Lab Brain Aging & Mental Hlth, Mol & Cognit Neurosci, Basel, Switzerland

[18] Univ Hosp Tubingen, Dept Radiol, Tubingen, Germany

[19] Univ Tubingen, Dept Biochem & Pharm, Tubingen, Germany

[20] Yerevan State Med Univ, Neurosci Lab, Yerevan, Armenia

[21] Yerevan State Med Univ, Dept Biochem, Yerevan, Armenia

[22] Yerevan State Med Univ, Dept Clin Pharmacol, Yerevan, Armenia

来源：

EBIOMEDICINE | 2020年 / 60卷

关键词：

Stem cells; Migration; Adhesion; Homing; Stroke; Glioma; MESENCHYMAL STROMAL CELLS; LUNG CLEARANCE RATE; DIVALENT-CATIONS; EXPRESSION; PROTEIN; CD44; GENE; TRANSDUCTION; INTEGRINS; APOPTOSIS;

D O I：

10.1016/j.ebiom.2020.102987

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Limited knowledge of stem cell therapies' mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested whether adhesion receptors and chemokine receptors on stem cells can be functionally modulated, and consequently if such modulation may substantially affect therapeutically relevant stem cell interactions with the host endothelium. Methods: We investigated the effects of cationic molecule polyethylenimine (PEI) treatment with or without nanoparticles on the functions of adhesion receptors and chemokine receptors of human bone marrow-derived Mesenchymal Stem Cells (MSC). Analyses included MSC functions in vitro, as well as homing and therapeutic efficacy in rodent models of central nervous system's pathologies in vivo. Findings: PEI treatment did not affect viability, immunomodulation or differentiation potential of MSC, but increased the CCR4 expression and functionally blocked their adhesion receptors, thus decreasing their adhesion capacity in vitro. Intravenously applied in a rat model of brain injury, the homing rate of PEI-MSC in the brain was highly increased with decreased numbers of adherent PEI-MSC in the lung vasculature. Moreover, in comparison to untreated MSC, PEI-MSC featured increased tumour directed migration in a mouse glioblastoma model, and superior therapeutic efficacy in a murine model of stroke. Interpretation: Balanced stem cell adhesion and migration in different parts of the vasculature and tissues together with the local microenvironment impacts their therapeutic efficacy. Funding: Robert Bosch Stiftung, IZEPHA grant, EU grant 7 FP Health (c) 2020 The Authors. Published by Elsevier B.V.

引用

页数：15

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