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Therapeutic Modulation of Mesenchymal Stem Cells for Effective Regenerative Medicine 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 16860

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Department of Pharmacy, Doctors Hospital, Augusta, GA 30909, USA
Interests: obesity; diabetes; retinopathy; ischemic vascular disease; diabetic microvascular complications
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Dear Colleagues,

Mesenchymal stem cells (MSCs), multipotent stem cells that can be isolated from various tissue sources, have been shown to regenerate various tissues of mesodermal origin. The therapeutic effect of MSCs is largely mediated via paracrine effects and the secretion of extensive bioactive molecules, known as the “secretome”. The regenerative benefit of the secretome has been attributed to MSC-derived extracellular vesicles as well as the release of trophic factors and cytokines that play neuroprotective, angiogenic, anti-inflammatory, and immune-modulatory roles.

The advancement of autologous MSC therapy or its secretome can be hindered when introduced back into a hostile/disease environment. Impaired endogenous MSC function, limited post-transplantation cell viability, and altered MSC immunomodulatory efficiency are a few examples. Thus, restoring the functional capabilities of these impaired MSCs prior to transplantation or utilizing the secretome is an effective strategy for promoting their ultimate success as repair mediators.

This Special Issue welcomes submissions of research and review articles on the following topics: (1) preclinical studies testing the impact of therapeutic modulators on MSC efficacy in animal models; (2) molecular mechanisms associated with therapeutic modulation; and (3) translational application of MSCs or the secretome in endocrine/metabolic disorders.

Prof. Azza B. El-Remessy
Guest Editor

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Keywords

  • mesenchymal stem cells (MSCs)
  • regenerative medicine
  • bioactive materials
  • cell differentiation/cell fate
  • survival/anti-apoptotic
  • angiogenesis/repair
  • neuroprotection
  • immune-modulation
  • inflammation
  • animal models

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Published Papers (4 papers)

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Research

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13 pages, 5961 KiB  
Article
Novel Methods to Mobilize, Isolate, and Expand Mesenchymal Stem Cells
by Cristiano P. Vieira, Taralyn M. McCarrel and Maria B. Grant
Int. J. Mol. Sci. 2021, 22(11), 5728; https://doi.org/10.3390/ijms22115728 - 27 May 2021
Cited by 10 | Viewed by 3932
Abstract
Numerous studies demonstrate the essential role of mesenchymal stem cells (MSCs) in the treatment of metabolic and inflammatory diseases, as these cells are known to modulate humoral and cellular immune responses. In this manuscript, we efficiently present two novel approaches to obtain MSCs [...] Read more.
Numerous studies demonstrate the essential role of mesenchymal stem cells (MSCs) in the treatment of metabolic and inflammatory diseases, as these cells are known to modulate humoral and cellular immune responses. In this manuscript, we efficiently present two novel approaches to obtain MSCs from equine or human sources. In our first approach, we used electro-acupuncture as previously described by our group to mobilize MSCs into the peripheral blood of horses. For equine MSC collection, culture, and expansion, we used the Miltenyi Biotec CliniMACS Prodigy system of automated cell manufacturing. Using this system, we were able to generate appoximately 100 MSC colonies that exhibit surface marker expression of CD105 (92%), CD90 (85%), and CD73 (88%) within seven days of blood collection. Our second approach utilized the iPSC embryoid bodies from healthy or diabetic subjects where the iPSCs were cultured in standard media (endothelial + mesoderm basal media). After 21 days, the cells were FACS sorted and exhibited surface marker expression of CD105, CD90, and CD73. Both the equine cells and the human iPSC-derived MSCs were able to differentiate into adipogenic, osteogenic, and chondrogenic lineages. Both methods described simple and highly efficient methods to produce cells with surface markers phenotypically considered as MSCs and may, in the future, facilitate rapid production of MSCs with therapeutic potential. Full article
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11 pages, 2656 KiB  
Article
In Situ Preconditioning of Human Mesenchymal Stem Cells Elicits Comprehensive Cardiac Repair Following Myocardial Infarction
by Woo-Sup Sim, Bong-Woo Park, Kiwon Ban and Hun-Jun Park
Int. J. Mol. Sci. 2021, 22(3), 1449; https://doi.org/10.3390/ijms22031449 - 1 Feb 2021
Cited by 7 | Viewed by 3355
Abstract
Human bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cell-based cardiac regenerative therapy. However, their clinical use has been significantly hampered by low survival and [...] Read more.
Human bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cell-based cardiac regenerative therapy. However, their clinical use has been significantly hampered by low survival and poor retention following administration into failing hearts. Here, to improve the therapeutic effectiveness of BM-MSCs, we examined a novel therapeutic platform named in situ preconditioning in a rat myocardial infarction (MI) model. In situ preconditioning was induced by a combinatory treatment of BM-MSCs with genetically engineered hepatocyte growth factor-expressing MSCs (HGF-eMSCs) and heart-derived extracellular matrix (hdECM) hydrogel. Subsequently, our results demonstrated that in situ preconditioning with cell mixture substantially improved the survival/retention of BM-MSCs in the MI-induced rat hearts. Enhanced retention of BM-MSCs ultimately led to a significant cardiac function improvement, which was derived from the protection of myocardium and enhancement of vessel formation in the MI hearts. The results provide compelling evidence that in situ preconditioning devised to improve the therapeutic potential of BM-MSCs can be an effective strategy to achieve cardiac repair of MI hearts. Full article
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Review

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31 pages, 993 KiB  
Review
Modulation of Mesenchymal Stem Cells for Enhanced Therapeutic Utility in Ischemic Vascular Diseases
by Sally L. Elshaer, Salma H. Bahram, Pranav Rajashekar, Rajashekhar Gangaraju and Azza B. El-Remessy
Int. J. Mol. Sci. 2022, 23(1), 249; https://doi.org/10.3390/ijms23010249 - 27 Dec 2021
Cited by 13 | Viewed by 4054
Abstract
Mesenchymal stem cells are multipotent stem cells isolated from various tissue sources, including but not limited to bone marrow, adipose, umbilical cord, and Wharton Jelly. Although cell-mediated mechanisms have been reported, the therapeutic effect of MSCs is now recognized to be primarily mediated [...] Read more.
Mesenchymal stem cells are multipotent stem cells isolated from various tissue sources, including but not limited to bone marrow, adipose, umbilical cord, and Wharton Jelly. Although cell-mediated mechanisms have been reported, the therapeutic effect of MSCs is now recognized to be primarily mediated via paracrine effects through the secretion of bioactive molecules, known as the “secretome”. The regenerative benefit of the secretome has been attributed to trophic factors and cytokines that play neuroprotective, anti-angiogenic/pro-angiogenic, anti-inflammatory, and immune-modulatory roles. The advancement of autologous MSCs therapy can be hindered when introduced back into a hostile/disease environment. Barriers include impaired endogenous MSCs function, limited post-transplantation cell viability, and altered immune-modulatory efficiency. Although secretome-based therapeutics have gained popularity, many translational hurdles, including the heterogeneity of MSCs, limited proliferation potential, and the complex nature of the secretome, have impeded the progress. This review will discuss the experimental and clinical impact of restoring the functional capabilities of MSCs prior to transplantation and the progress in secretome therapies involving extracellular vesicles. Modulation and utilization of MSCs–secretome are most likely to serve as an effective strategy for promoting their ultimate success as therapeutic modulators. Full article
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17 pages, 1135 KiB  
Review
Pulsed Electromagnetic Field Stimulation in Osteogenesis and Chondrogenesis: Signaling Pathways and Therapeutic Implications
by Katia Varani, Fabrizio Vincenzi, Silvia Pasquini, Irene Blo, Simona Salati, Matteo Cadossi and Monica De Mattei
Int. J. Mol. Sci. 2021, 22(2), 809; https://doi.org/10.3390/ijms22020809 - 15 Jan 2021
Cited by 43 | Viewed by 4755
Abstract
Mesenchymal stem cells (MSCs) are the main cell players in tissue repair and thanks to their self-renewal and multi-lineage differentiation capabilities, they gained significant attention as cell source for tissue engineering (TE) approaches aimed at restoring bone and cartilage defects. Despite significant progress, [...] Read more.
Mesenchymal stem cells (MSCs) are the main cell players in tissue repair and thanks to their self-renewal and multi-lineage differentiation capabilities, they gained significant attention as cell source for tissue engineering (TE) approaches aimed at restoring bone and cartilage defects. Despite significant progress, their therapeutic application remains debated: the TE construct often fails to completely restore the biomechanical properties of the native tissue, leading to poor clinical outcomes in the long term. Pulsed electromagnetic fields (PEMFs) are currently used as a safe and non-invasive treatment to enhance bone healing and to provide joint protection. PEMFs enhance both osteogenic and chondrogenic differentiation of MSCs. Here, we provide extensive review of the signaling pathways modulated by PEMFs during MSCs osteogenic and chondrogenic differentiation. Particular attention has been given to the PEMF-mediated activation of the adenosine signaling and their regulation of the inflammatory response as key player in TE approaches. Overall, the application of PEMFs in tissue repair is foreseen: (1) in vitro: to improve the functional and mechanical properties of the engineered construct; (2) in vivo: (i) to favor graft integration, (ii) to control the local inflammatory response, and (iii) to foster tissue repair from both implanted and resident MSCs cells. Full article
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