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Cells
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Mesenchymal Stromal Cell‐Based Therapy
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Mesenchymal Stromal Cell‐Based Therapy

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Methods".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 21505

Special Issue Editors

Prof. Martin J. Hoogduijn

E-Mail Website
Guest Editor
Erasmus University Medical Center, Rotterdam, The Netherlands
Interests: mesenchymal stem/stromal cells; regeneration; immunomodulation; cell therapy; organoids
Prof. Dr. Marc-H. Dahlke

E-Mail Website
Guest Editor
Robert-Bosch-Hospital and Margarete-Fischer-Bosch Institute, Stuttgart, Germany
Interests: immunobiology of stem cells; cancer immunotherapy; surgery

Special Issue Information

Dear Colleagues, 

Mesenchymal stromal cells (MSC) have found their way to the arena of clinical testing in a variety of areas, including bone repair, hematological and autoimmune disease, and organ transplantation. In recent years, new insights in the mechanisms of action of MSC have helped to shape clinical trials. It has become clear that the interaction between MSC and recipient (immune) cells is of utter importance for the therapeutic effect of MSC, and furthermore, novel mediators such as extracellular vesicles, have been identified to play a role in the effects of MSC. Some of these mediators may potentially be used as an alternative to MSC therapy. To understand how the therapeutic effects of MSC can be applied efficiently and which indications are receptive for MSC therapy, it is of great importance to monitor the effects of MSC after administration in detail. This Special Issue on mesenchymal stromal cell-based therapy aims to include original data papers and reviews on the mechanisms of action of MSC in a therapeutic context as well as papers monitoring the effects of MSC in preclinical models and clinical studies.

Prof. Martin J. Hoogduijn
Dr. Marc Hendrik Dahlke
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mesenchymal stromal cells
  • mesenchymal stem cells
  • regenerative cell therapy
  • immunomodulatory cell therapy
  • immunobiology of stem cells
  • cell and organ transplantation
  • organ failure therapy
  • sepsis and pulmonary syndromes and therapy

Published Papers (7 papers)

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Editorial

Jump to: Research, Review, Other

3 pages, 177 KiB  
Editorial
Mesenchymal Stromal Cell-Based Therapy
by Dina Mönch, Marlies E. J. Reinders, Martin J. Hoogduijn and Marc-Hendrik Dahlke
Cells 2023, 12(4), 559; https://doi.org/10.3390/cells12040559 - 9 Feb 2023
Cited by 1 | Viewed by 1124
Abstract
The use of mesenchymal stromal cells (MSCs) for clinical application is intensively investigated for a variety of areas, such as bone repair, haematological and autoimmune diseases, and solid organ transplantation [...] Full article
(This article belongs to the Special Issue Mesenchymal Stromal Cell‐Based Therapy)

Research

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20 pages, 2486 KiB  
Article
Effect of Cell Therapy and Exercise Training in a Stroke Model, Considering the Cell Track by Molecular Image and Behavioral Analysis
by Mariana P. Nucci, Fernando A. Oliveira, João M. Ferreira, Yolanda O. Pinto, Arielly H. Alves, Javier B. Mamani, Leopoldo P. Nucci, Nicole M. E. Valle and Lionel F. Gamarra
Cells 2022, 11(3), 485; https://doi.org/10.3390/cells11030485 - 30 Jan 2022
Cited by 7 | Viewed by 2675
Abstract
The goal of this study is to see how combining physical activity with cell treatment impacts functional recovery in a stroke model. Molecular imaging and multimodal nanoparticles assisted in cell tracking and longitudinal monitoring (MNP). The viability of mesenchymal stem cell (MSC) was [...] Read more.
The goal of this study is to see how combining physical activity with cell treatment impacts functional recovery in a stroke model. Molecular imaging and multimodal nanoparticles assisted in cell tracking and longitudinal monitoring (MNP). The viability of mesenchymal stem cell (MSC) was determined using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and bioluminescent image (BLI) after lentiviral transduction and MNP labeling. At random, the animals were divided into 5 groups (control-G1, and experimental G2-G5). The photothrombotic stroke induction was confirmed by local blood perfusion reduction and Triphenyltetrazolium chloride (TTC), and MSC in the G3 and G5 groups were implanted after 24 h, with BLI and near-infrared fluorescence image (NIRF) tracking these cells at 28 h, 2, 7, 14, and 28 days. During a 28-day period, the G5 also conducted physical training, whereas the G4 simply did the training. At 0, 7, 14, and 28 days, the animals were functionally tested using a cylinder test and a spontaneous motor activity test. MNP internalization in MSC was confirmed using brightfield and fluorescence microscopy. In relation to G1 group, only 3% of cell viability reduced. The G2–G5 groups showed more than 69% of blood perfusion reduction. The G5 group performed better over time, with a progressive recovery of symmetry and an increase of fast vertical movements. Up to 7 days, BLI and NIRF followed MSC at the damaged site, demonstrating a signal rise that could be connected to cell proliferation at the injury site during the acute phase of stroke. Local MSC therapy mixed with physical activity resulted in better results in alleviating motor dysfunction, particularly during the acute period. When it comes to neurorehabilitation, this alternative therapy could be a suitable fit. Full article
(This article belongs to the Special Issue Mesenchymal Stromal Cell‐Based Therapy)
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19 pages, 668 KiB  
Article
MSC Manufacturing for Academic Clinical Trials: From a Clinical-Grade to a Full GMP-Compliant Process
by Chantal Lechanteur, Alexandra Briquet, Virginie Bettonville, Etienne Baudoux and Yves Beguin
Cells 2021, 10(6), 1320; https://doi.org/10.3390/cells10061320 - 26 May 2021
Cited by 37 | Viewed by 4975
Abstract
Following European regulation 1394/2007, mesenchymal stromal cell (MSCs) have become an advanced therapy medicinal product (ATMP) that must be produced following the good manufacturing practice (GMP) standards. We describe the upgrade of our existing clinical-grade MSC manufacturing process to obtain GMP certification. Staff [...] Read more.
Following European regulation 1394/2007, mesenchymal stromal cell (MSCs) have become an advanced therapy medicinal product (ATMP) that must be produced following the good manufacturing practice (GMP) standards. We describe the upgrade of our existing clinical-grade MSC manufacturing process to obtain GMP certification. Staff organization, premises/equipment qualification and monitoring, raw materials management, starting materials, technical manufacturing processes, quality controls, and the release, thawing and infusion were substantially reorganized. Numerous studies have been carried out to validate cultures and demonstrate the short-term stability of fresh or thawed products, as well their stability during long-term storage. Detailed results of media simulation tests, validation runs and early MSC batches are presented. We also report the validation of a new variant of the process aiming to prepare fresh MSCs for the treatment of specific lesions of Crohn’s disease by local injection. In conclusion, we have successfully ensured the adaptation of our clinical-grade MSC production process to the GMP requirements. The GMP manufacturing of MSC products is feasible in the academic setting for a limited number of batches with a significant cost increase, but moving to large-scale production necessary for phase III trials would require the involvement of industrial partners. Full article
(This article belongs to the Special Issue Mesenchymal Stromal Cell‐Based Therapy)
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Review

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21 pages, 1203 KiB  
Review
Cell Therapy of Stroke: Do the Intra-Arterially Transplanted Mesenchymal Stem Cells Cross the Blood–Brain Barrier?
by Konstantin N. Yarygin, Daria D. Namestnikova, Kirill K. Sukhinich, Ilya L. Gubskiy, Alexander G. Majouga and Irina V. Kholodenko
Cells 2021, 10(11), 2997; https://doi.org/10.3390/cells10112997 - 3 Nov 2021
Cited by 14 | Viewed by 3671
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Mesenchymal Stromal Cell‐Based Therapy)
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14 pages, 1088 KiB  
Review
Preconditioned Mesenchymal Stromal Cells to Improve Allotransplantation Outcome
by Hui-Yun Cheng, Madonna Rica Anggelia, Cheng-Hung Lin and Chih-Fan Lin
Cells 2021, 10(9), 2325; https://doi.org/10.3390/cells10092325 - 6 Sep 2021
Cited by 5 | Viewed by 2553
Abstract
Mesenchymal stromal cells (MSCs) are tissue-derived progenitor cells with immunomodulatory as well as multilineage differentiation capacities, and have been widely applied as cellular therapeutics in different disease systems in both preclinical models and clinical studies. Although many studies have applied MSCs in different [...] Read more.
Mesenchymal stromal cells (MSCs) are tissue-derived progenitor cells with immunomodulatory as well as multilineage differentiation capacities, and have been widely applied as cellular therapeutics in different disease systems in both preclinical models and clinical studies. Although many studies have applied MSCs in different types of allotransplantation, the efficacy varies. It has been demonstrated that preconditioning MSCs prior to in vivo administration may enhance their efficacy. In the field of organ/tissue allotransplantation, many recent studies have shown that preconditioning of MSCs with (1) pretreatment with bioactive factors or reagents such as cytokines, or (2) specific gene transfection, could prolong allotransplant survival and improve allotransplant function. Herein, we review these preconditioning strategies and discuss potential directions for further improvement. Full article
(This article belongs to the Special Issue Mesenchymal Stromal Cell‐Based Therapy)
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17 pages, 2348 KiB  
Review
Influence of Hypothermic Storage Fluids on Mesenchymal Stem Cell Stability: A Comprehensive Review and Personal Experience
by Aneta Ścieżyńska, Marta Soszyńska, Patrycja Szpak, Natalia Krześniak, Jacek Malejczyk and Ilona Kalaszczyńska
Cells 2021, 10(5), 1043; https://doi.org/10.3390/cells10051043 - 28 Apr 2021
Cited by 14 | Viewed by 3474
Abstract
Mesenchymal stem cells have generated a great deal of interest due to their potential use in regenerative medicine and tissue engineering. Examples illustrating their therapeutic value across various in vivo models are demonstrated in the literature. However, some clinical trials have not proved [...] Read more.
Mesenchymal stem cells have generated a great deal of interest due to their potential use in regenerative medicine and tissue engineering. Examples illustrating their therapeutic value across various in vivo models are demonstrated in the literature. However, some clinical trials have not proved their therapeutic efficacy, showing that translation into clinical practice is considerably more difficult and discrepancies in clinical protocols can be a source of failure. Among the critical factors which play an important role in MSCs’ therapeutic efficiency are the method of preservation of the stem cell viability and various characteristics during their storage and transportation from the GMP production facility to the patient’s bedside. The cell storage medium should be considered a key factor stabilizing the environment and greatly influencing cell viability and potency and therefore the effectiveness of advanced therapy medicinal product (ATMP) based on MSCs. In this review, we summarize data from 826 publications concerning the effect of the most frequently used cell preservation solutions on MSC potential as cell-based therapeutic medicinal products. Full article
(This article belongs to the Special Issue Mesenchymal Stromal Cell‐Based Therapy)
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Other

12 pages, 309 KiB  
Commentary
How to Make Sense out of 75,000 Mesenchymal Stromal Cell Publications?
by Dina Mönch, Marlies E. J. Reinders, Marc H. Dahlke and Martin J. Hoogduijn
Cells 2022, 11(9), 1419; https://doi.org/10.3390/cells11091419 - 22 Apr 2022
Cited by 5 | Viewed by 2124
Abstract
Mesenchymal stromal cells have been the subject of an expanding number of studies over the past decades. Today, over 75,000 publications are available that shine light on the biological properties and therapeutic effects of these versatile cells in numerous pre-clinical models and early-phase [...] Read more.
Mesenchymal stromal cells have been the subject of an expanding number of studies over the past decades. Today, over 75,000 publications are available that shine light on the biological properties and therapeutic effects of these versatile cells in numerous pre-clinical models and early-phase clinical trials. The massive number of papers makes it hard for researchers to comprehend the whole field, and furthermore, they give the impression that mesenchymal stromal cells are wonder cells that are curative for any condition. It is becoming increasingly difficult to dissect how and for what conditions mesenchymal stromal cells exhibit true and reproducible therapeutic effects. This article tries to address the question how to make sense of 75,000, and still counting, publications on mesenchymal stromal cells. Full article
(This article belongs to the Special Issue Mesenchymal Stromal Cell‐Based Therapy)
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