scholarly journals Persistency of Mesenchymal Stromal/Stem Cells in Lungs

Author(s):  
Erica Ferrini ◽  
Fabio Franco Stellari ◽  
Valentina Franceschi ◽  
Francesca Macchi ◽  
Luca Russo ◽  
...  

Mesenchymal stromal/stem cells (MSCs) are a fibroblast-like cell population with high regenerative potential that can be isolated from many different tissues. Several data suggest MSCs as a therapeutic tool capable of migrating to a site of injury and guide tissue regeneration mainly through their secretome. Pulmonary first-pass effect occurs during intravenous administration of MSCs, where 50 to 80% of the cells tend to localize in the lungs. This phenomenon has been exploited to study MSC potential therapeutic effects in several preclinical models of lung diseases. Data demonstrated that, regardless of the lung disease severity and the delivery route, MSCs were not able to survive longer than 24 h in the respiratory tract but still surprisingly determined a therapeutic effect. In this work, two different mouse bone marrow-derived mesenchymal stromal/stem cell (mBM-MSC) lines, stably transduced with a third-generation lentiviral vector expressing luciferase and green fluorescent protein reporter genes tracking MSCs in vivo biodistribution and persistency, have been generated. Cells within the engrafted lung were in vivo traced using the high-throughput bioluminescence imaging (BLI) technique, with no invasiveness on animal, minimizing biological variations and costs. In vivo BLI analysis allowed the detection and monitoring of the mBM-MSC clones up to 28 days after implantation independently from the delivery route. This longer persistency than previously observed (24 h) could have a strong impact in terms of pharmacokinetics and pharmacodynamics of MSCs as a therapeutic tool.

2021 ◽  
Author(s):  
Erica Ferrini ◽  
Fabio Franco Stellari ◽  
Valentina Franceschi ◽  
Francesca Macchi ◽  
Luca Russo ◽  
...  

Abstract Background. Mesenchymal stromal/stem Cells (MSCs) are a fibroblast-like cell population with high regenerative potential that can be isolated from many different tissues. Several data suggest MSCs as a therapeutic tool capable of migrating to a site of injury and guide tissue regeneration mainly through their secretome. Pulmonary first-pass effect occurs during intravenous administration of MSCs, where 50 to 80% of the cells tend to localize in the lungs. This phenomenon has been exploited to study MSCs potential therapeutic effects in several pre-clinical models of lung diseases. Data demonstrated that, regardless the lung disease severity and the delivery route, MSCs were not able to survive longer than 24h in the respiratory tract, but still surprisingly determining a therapeutic effect. Methods. In this work, two different mouse bone marrow derived MSCs (mBM-MSCs) lines, stably transduced with a third-generation lentiviral vector expressing Luciferase and GFP reporter genes tracking MSCs in vivo biodistribution and persistency, have been generated. Results. Cells within the engrafted lung were in vivo traced using the high throughput Bioluminescence Imaging (BLI) technique, with no invasiveness on animal, minimizing biological variations and costs. In vivo BLI analysis allowed the detection and monitoring of the mBM-MSC clones up to 28 days after implantation, independently from the delivery route. Conclusions. This longer persistency, than previously observed (24 hours), could have a strong impact in terms of pharmacokinetic (PK) and pharmacodynamics (PD) of MSCs as a therapeutic tool.


Author(s):  
Maryam Kasraeian ◽  
Elahe Ghasemi ◽  
Mehdi Dianatpour ◽  
Nader Tanideh ◽  
Iman Razeghian Jahromi ◽  
...  

Background: Animals can play an important role in preparing tissues for human through the development of xenotransplantation protocols. The most common problem with liver transplantation like any other organ transplantation is organ supply shortage. Objective: To evaluate the in utero xenotransplantation of mouse bone marrow-derived stromal/stem cells (BMSCs) to the liver of rat fetus to produce mouse liver tissue. Materials and Methods: BMSCs were isolated and confirmed from enhanced green fluorescent protein (eGFP)-genetic labeled mice. Using a microinjection protocol, mice BMSCs were injected into the liver of rat fetuses in utero on day 14 of pregnancy. After birth, livers were collected and the presence of mice eGFP-positive cells in rat livers was evaluated through polymerase chain reaction. Results: The eGFP mRNA was detected in the liver of injected infant rats. BMSCs of adult mice were capable to remain functional probably as hepatocyte-like cells in liver of infant rats after in utero xenotransplantation. Conclusion: BMSCs have the potential for intrauterine xenotransplantation for the treatment of liver dysfunction before birth. This method can also be used for xenoproduction of liver tissue for transplantation. Key words: Xenotransplantation, Liver, Bone marrow, Stromal/stem cell, Murine.


2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Ross E. B. Fitzsimmons ◽  
Matthew S. Mazurek ◽  
Agnes Soos ◽  
Craig A. Simmons

As a result of over five decades of investigation, mesenchymal stromal/stem cells (MSCs) have emerged as a versatile and frequently utilized cell source in the fields of regenerative medicine and tissue engineering. In this review, we summarize the history of MSC research from the initial discovery of their multipotency to the more recent recognition of their perivascular identity in vivo and their extraordinary capacity for immunomodulation and angiogenic signaling. As well, we discuss long-standing questions regarding their developmental origins and their capacity for differentiation toward a range of cell lineages. We also highlight important considerations and potential risks involved with their isolation, ex vivo expansion, and clinical use. Overall, this review aims to serve as an overview of the breadth of research that has demonstrated the utility of MSCs in a wide range of clinical contexts and continues to unravel the mechanisms by which these cells exert their therapeutic effects.


2022 ◽  
Vol 23 (2) ◽  
pp. 863
Author(s):  
Alessia Gallo ◽  
Nicola Cuscino ◽  
Flavia Contino ◽  
Matteo Bulati ◽  
Mariangela Pampalone ◽  
...  

Mesenchymal stromal/stem cells (MSCs) are believed to function in vivo as a homeostatic tool that shows therapeutic properties for tissue repair/regeneration. Conventionally, these cells are expanded in two-dimensional (2D) cultures, and, in that case, MSCs undergo genotypic/phenotypic changes resulting in a loss of their therapeutic capabilities. Moreover, several clinical trials using MSCs have shown controversial results with moderate/insufficient therapeutic responses. Different priming methods were tested to improve MSC effects, and three-dimensional (3D) culturing techniques were also examined. MSC spheroids display increased therapeutic properties, and, in this context, it is crucial to understand molecular changes underlying spheroid generation. To address these limitations, we performed RNA-seq on human amnion-derived MSCs (hAMSCs) cultured in both 2D and 3D conditions and examined the transcriptome changes associated with hAMSC spheroid formation. We found a large number of 3D culture-sensitive genes and identified selected genes related to 3D hAMSC therapeutic effects. In particular, we observed that these genes can regulate proliferation/differentiation, as well as immunomodulatory and angiogenic processes. We validated RNA-seq results by qRT-PCR and methylome analysis and investigation of secreted factors. Overall, our results showed that hAMSC spheroid culture represents a promising approach to cell-based therapy that could significantly impact hAMSC application in the field of regenerative medicine.


Author(s):  
Basem M. Abdallah ◽  
Hany M. Khattab

: The isolation and culture of murine bone marrow-derived mesenchymal stromal stem cells (mBMSCs) have attracted great interest in terms of the pre-clinical applications of stem cells in tissue engineering and regenerative medicine. In addition, culturing mBMSCs is important for studying the molecular mechanisms of bone remodelling using relevant transgenic mice. Several factors have created challenges in the isolation and high-yield expansion of homogenous mBMSCs; these factors include low frequencies of bone marrow-derived mesenchymal stromal stem cells (BMSCs) in bone marrow, variation among inbred mouse strains, contamination with haematopoietic progenitor cells (HPCs), the replicative senescence phenotype and cellular heterogeneity. In this review, we provide an overview of nearly all protocols used for isolating and culturing mBMSCs with the aim of clarifying the most important guidelines for culturing highly purified mBMSC populations retaining in vitro and in vivo differentiation potential.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ruijie Zeng ◽  
Jinghua Wang ◽  
Zewei Zhuo ◽  
Yujun Luo ◽  
Weihong Sha ◽  
...  

AbstractNecrotizing enterocolitis (NEC) is a devastating disease predominately affecting neonates. Despite therapeutic advances, NEC remains the leading cause of mortality due to gastrointestinal conditions in neonates. Stem cells have been exploited in various diseases, and the application of different types of stem cells in the NEC therapy is explored in the past decade. However, stem cell transplantation possesses several deficiencies, and exosomes are considered potent alternatives. Exosomes, especially those derived from stem cells and breast milk, demonstrate beneficial effects for NEC both in vivo and in vitro and emerge as promising options for clinical practice. In this review, the function and therapeutic effects of stem cells and exosomes for NEC are investigated and summarized, which provide insights for the development and application of novel therapeutic strategies in pediatric diseases. Further elucidation of mechanisms, improvement in preparation, bioengineering, and administration, as well as rigorous clinical trials are warranted.


2021 ◽  
Author(s):  
Xiuying Li ◽  
Zhenhong Wei ◽  
Binxi Li ◽  
Jing Li ◽  
Huiying Lv ◽  
...  

Correction for ‘In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model’ by Xiuying Li et al., Biomater. Sci., 2019, 7, 2861–2872, DOI: 10.1039/C9BM00242A.


Nanoscale ◽  
2020 ◽  
Author(s):  
Naishun Liao ◽  
Da Zhang ◽  
Ming Wu ◽  
Huang-Hao Yang ◽  
Xiaolong Liu ◽  
...  

Adipose tissue derived mesenchymal stem cell (ADSC)-based therapy is attractive for liver diseases, but the long-term therapeutic outcome is still far from satisfaction due to low hepatic engraftment efficiency of...


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