Comparison of the Regenerative Potential for Lung Tissue of Mesenchymal Stromal Cells from Different Sources/Locations Within the Body

Author(s):  
Sara Rolandsson Enes ◽  
Gunilla Westergren-Thorsson
2021 ◽  
Vol 10 (13) ◽  
pp. 2925
Author(s):  
Manuel Sanchez-Diaz ◽  
Maria I. Quiñones-Vico ◽  
Raquel Sanabria de la Torre ◽  
Trinidad Montero-Vílchez ◽  
Alvaro Sierra-Sánchez ◽  
...  

Mesenchymal Stromal Cells (MSCs) are of great interest in cellular therapy. Different routes of administration of MSCs have been described both in pre-clinical and clinical reports. Knowledge about the fate of the administered cells is critical for developing MSC-based therapies. The aim of this review is to describe how MSCs are distributed after injection, using different administration routes in animal models and humans. A literature search was performed in order to consider how MSCs distribute after intravenous, intraarterial, intramuscular, intraarticular and intralesional injection into both animal models and humans. Studies addressing the biodistribution of MSCs in “in vivo” animal models and humans were included. After the search, 109 articles were included in the review. Intravenous administration of MSCs is widely used; it leads to an initial accumulation of cells in the lungs with later redistribution to the liver, spleen and kidneys. Intraarterial infusion bypasses the lungs, so MSCs distribute widely throughout the rest of the body. Intramuscular, intraarticular and intradermal administration lack systemic biodistribution. Injection into various specific organs is also described. Biodistribution of MSCs in animal models and humans appears to be similar and depends on the route of administration. More studies with standardized protocols of MSC administration could be useful in order to make results homogeneous and more comparable.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2860
Author(s):  
Dennis M. L. W. Kruk ◽  
Marissa Wisman ◽  
Jacobien A. Noordhoek ◽  
Mehmet Nizamoglu ◽  
Marnix R. Jonker ◽  
...  

COPD is characterized by irreversible lung tissue damage. We hypothesized that lung-derived mesenchymal stromal cells (LMSCs) reduce alveolar epithelial damage via paracrine processes, and may thus be suitable for cell-based strategies in COPD. We aimed to assess whether COPD-derived LMSCs display abnormalities. LMSCs were isolated from lung tissue of severe COPD patients and non-COPD controls. Effects of LMSC conditioned-medium (CM) on H2O2-induced, electric field- and scratch-injury were studied in A549 and NCI-H441 epithelial cells. In organoid models, LMSCs were co-cultured with NCI-H441 or primary lung cells. Organoid number, size and expression of alveolar type II markers were assessed. Pre-treatment with LMSC-CM significantly attenuated oxidative stress-induced necrosis and accelerated wound repair in A549. Co-culture with LMSCs supported organoid formation in NCI-H441 and primary epithelial cells, resulting in significantly larger organoids with lower type II-marker positivity in the presence of COPD-derived versus control LMSCs. Similar abnormalities developed in organoids from COPD compared to control-derived lung cells, with significantly larger organoids. Collectively, this indicates that LMSCs’ secretome attenuates alveolar epithelial injury and supports epithelial repair. Additionally, LMSCs promote generation of alveolar organoids, with abnormalities in the supportive effects of COPD-derived LMCS, reflective of impaired regenerative responses of COPD distal lung cells.


2020 ◽  
Vol 21 (7) ◽  
pp. 2310 ◽  
Author(s):  
El-Mustapha Haddouti ◽  
Thomas M. Randau ◽  
Cäcilia Hilgers ◽  
Werner Masson ◽  
Klaus J. Walgenbach ◽  
...  

Currently, there is an increasing focus on mesenchymal stromal cells (MSC) as therapeutic option in bone pathologies as well as in general regenerative medicine. Although human MSCs have been extensively characterized and standardized, ovine MSCs are poorly understood. This limitation hampers clinical progress, as sheep are an excellent large animal model for orthopedic studies. Our report describes a direct comparison of human and ovine MSCs from three corresponding sources under the same conditions. All MSCs presented solid growth behavior and potent immunomodulatory capacities. Additionally, we were able to identify common positive (CD29, CD44, CD73, CD90, CD105, CD166) and negative (CD14, CD34, CD45, HLA-DR) surface markers. Although both human and ovine MSCs showed strong osteogenic potential, direct comparison revealed a slower mineralization process in ovine MSCs. Regarding gene expression level, both human and ovine MSCs presented a comparable up-regulation of Runx2 and a trend toward down-regulation of Col1A during osteogenic differentiation. In summary, this side by side comparison defined phenotypic similarities and differences of human and ovine MSCs from three different sources, thereby contributing to a better characterization and standardization of ovine MSCs. The key findings shown in this report demonstrate the utility of ovine MSCs in preclinical studies for MSC-based therapies.


2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Menghui Jiang ◽  
Tianlin Gao ◽  
Yuansheng Liu ◽  
Xue Cao ◽  
Yanting Li ◽  
...  

Abstract Mesenchymal stromal cells (MSCs) widely exist in many tissues and have multiple differentiation potential and immunomodulatory capacities. Recently, MSCs have become promising tools for the treatment of various degenerative disorders and autoimmune diseases. The properties of MSCs could be modified in different microenvironments. Thus, it is important to explore the factors controlling MSC function. The presence of Toll-like receptors (TLRs) in MSCs was demonstrated according to previous studies. Consistently, we also illustrated the expression of TLRs in both murine and human MSCs, and displayed that the expression patterns of TLRs in MSCs from different sources. Furthermore, we explored the role of TLR and TLR signaling pathway in MSCs. Interestingly, activation of TLR4-induced expression of cytokines and some specific genes in MSCs. However, MSCs retained much lower mRNA level compared with macrophages. We explored the expression of CD14 in MSCs from different sources, which played a vital role in TLR4 signaling pathway, and found that MSCs are almost negative for CD14. Moreover, only partial activation of TLR4 signaling pathway was observed in MSCs, with no activation of AKT, NF-κB and P38. Here, in the study we defined TLR expression, function and activation in MSCs, which is critical for designing MSC-based therapies.


Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1162
Author(s):  
Suzanne J. K. Mund ◽  
Eiko Kawamura ◽  
Awang Hazmi Awang-Junaidi ◽  
John Campbell ◽  
Bruce Wobeser ◽  
...  

Limb wounds on horses are often slow to heal and are prone to developing exuberant granulation tissue (EGT) and close primarily through epithelialization, which results in a cosmetically inferior and non-durable repair. In contrast, wounds on the body heal rapidly and primarily through contraction and rarely develop EGT. Intravenous (IV) multipotent mesenchymal stromal cells (MSCs) are promising. They home and engraft to cutaneous wounds and promote healing in laboratory animals, but this has not been demonstrated in horses. Furthermore, the clinical safety of administering >1.00 × 108 allogeneic MSCs IV to a horse has not been determined. A proof-of-principle pilot project was performed with two horses that were administered 1.02 × 108 fluorescently labeled allogeneic cord blood-derived MSCs (CB-MSCs) following wound creation on the forelimb and thorax. Wounds and contralateral non-wounded skin were sequentially biopsied on days 0, 1, 2, 7, 14, and 33 and evaluated with confocal microscopy to determine presence of homing and engraftment. Results confirmed preferential homing and engraftment to wounds with persistence of CB-MSCs at 33 days following wound creation, without clinically adverse reactions to the infusion. The absence of overt adverse reactions allows further studies to determine effects of IV CB-MSCs on equine wound healing.


2017 ◽  
Vol 6 (6) ◽  
pp. 1557-1567 ◽  
Author(s):  
Soraia C. Abreu ◽  
Mariana A. Antunes ◽  
Debora G. Xisto ◽  
Fernanda F. Cruz ◽  
Vivian C. Branco ◽  
...  

Author(s):  
Måns Kadefors ◽  
Sara Rolandsson Enes ◽  
Maria Weitoft ◽  
Stefan Scheding ◽  
Gunilla Westergren-Thorsson

2014 ◽  
Vol 7 (1) ◽  
pp. 826 ◽  
Author(s):  
Janina Burk ◽  
Claudia Gittel ◽  
Sandra Heller ◽  
Bastian Pfeiffer ◽  
Felicitas Paebst ◽  
...  

2020 ◽  
Vol 36 (4) ◽  
pp. 74-79
Author(s):  
Т.В. Bukharova ◽  
A.A. Buianova ◽  
K.S. Davygora ◽  
D.V. Goldshtein

Multipotent mesenchymal stromal cells (MSCs) can be used as a model for the development of gene and cell technologies and as a means of delivering nucleic acids to the body, including as part of tissue-engineering constructs. Small interfering RNA (siRNA) molecules acting by the RNA interference mechanism are a high-precision tool for genetic silencing of target mRNA transcripts. The search for low toxic and highly efficient transfection agents for delivery of siRNA or other nucleic acids to MSCs is an urgent task for the development of therapy based on these molecules. A comparative evaluation of five transfection agents showed that compounds based on cationic polymers were more efficient in delivering siRNA molecules than liposomes, while the cytotoxicity of all tested reagents was independent of their chemical structure. For two of the three transfection agents selected according to their efficiency and belonging to different classes, TurboFect and Lipofectamine® 3000, a moderate effect on cell viability was revealed. The results obtained allow us to recommend TurboFect and Lipofectamine® 3000 as highly efficient and relatively low-toxic agents for transfection of MSCs cultures. multipotent mesenchymal stromal cells, siRNA, transfection, lipofection, cationic lipids, cationic polymers, polyethyleneimine. The authors are grateful to staff of functional genomics laboratory of Research Centre for Medical Genetics Skoblova M.Yu. and Krivosheeva I.A., for technical and methodological assistance. The work was financially supported by the Ministry of Science and Higher Education of the Russian Federation within the state assignment for Research Centre for Medical Genetics.


Sign in / Sign up

Export Citation Format

Share Document