Cell Therapy of Stroke: Do the Intra-Arterially Transplanted Mesenchymal Stem Cells Cross the Blood–Brain Barrier?

Interesting. 

Paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. ... Factors then travel to nearby cells in which the gradient of factor received determines the outcome.

Cell Therapy of Stroke: Do the Intra-Arterially Transplanted Mesenchymal Stem Cells Cross the Blood–Brain Barrier?

Konstantin N. Yarygin 1,* , Daria D. Namestnikova 2,3 , Kirill K. Sukhinich 4 , Ilya L. Gubskiy 2,3 , Alexander G. Majouga 5 and Irina V. Kholodenko 1


 Citation: Yarygin, K.N.; Namestnikova, D.D.; Sukhinich, K.K.; Gubskiy, I.L.; Majouga, A.G.; Kholodenko, I.V. Cell Therapy of Stroke: Do the Intra-Arterially Transplanted Mesenchymal Stem Cells Cross the Blood–Brain Barrier? Cells 2021, 10, 2997. https://doi.org/10.3390/ cells10112997 Academic Editors: Martin J. Hoogduijn and Marc-H. Dahlke Received: 27 September 2021 Accepted: 1 November 2021 Published: 3 November 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Laboratory of Cell Biology, Orekhovich Institute of Biomedical Chemistry, 119435 Moscow, Russia; irkhol@yandex.ru 2 Pirogov Russian National Research Medical University of the ministry of Healthcare of the Russian Federation, 117997 Moscow, Russia; dadnam89@gmail.com (D.D.N.); gubskiy.ilya@gmail.com (I.L.G.) 3 Radiology and Clinical Physiology Scientific Research Center, Federal Center of Brain Research and Neurotechnologies of the Federal Medical Biological Agency, 117513 Moscow, Russia 4 Laboratory of Problems of Regeneration, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, 119334 Moscow, Russia; sukhinichkirill@gmail.com 5 D. Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russia; alexander.majouga@gmail.com * Correspondence: kyarygin@yandex.ru 

Abstract: 

Animal model studies and first clinical trials have demonstrated the safety and efficacy of the mesenchymal stem cells’ (MSCs) transplantation in stroke. Intra-arterial (IA) administration looks especially promising, since it provides targeted cell delivery to the ischemic brain, is highly effective, and can be safe as long as the infusion is conducted appropriately. However, wider clinical application of the IA MSCs transplantation will only be possible after a better understanding of the mechanism of their therapeutic action is achieved. On the way to achieve this goal, the study of transplanted cells’ fate and their interactions with the blood–brain barrier (BBB) structures could be one of the key factors. In this review, we analyze the available data concerning one of the most important aspects of the transplanted MSCs’ action—the ability of cells to cross the blood–brain barrier (BBB) in vitro and in vivo after IA administration into animals with experimental stroke. The collected data show that some of the transplanted MSCs temporarily attach to the walls of the cerebral vessels and then return to the bloodstream or penetrate the BBB and either undergo homing in the perivascular space or penetrate deeper into the parenchyma. Transmigration across the BBB is not necessary for the induction of therapeutic effects, which can be incited through a paracrine mechanism even by cells located inside the blood vessels.