Five Decades Later, Are Mesenchymal Stem Cells Still Relevant?

Gomez-Salazar, Mario; Gonzalez-Galofre, Zaniah N.; Casamitjana, Joan; Crisan, Mihaela; James, Aaron W.; Péault, Bruno

doi:10.3389/fbioe.2020.00148

Cited by 121 publications

(103 citation statements)

References 165 publications

(183 reference statements)

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“…The source of cells producing ECM is of great importance for realizing its functional role (Cramer and Badylak, 2019). Among other cell types MSCs represent a promising source of multipotent adult stem and progenitor cells for cell therapy and tissue engineering (Lukomska et al, 2019;Gomez-Salazar et al, 2020). They play an important role in maintenance of hematopoietic stem cell niche and are considered as a critical stem cell niche component in different tissues (Kfoury and Scadden, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…It is well-known that mesenchymal stem/stromal cells (MSCs) play a key role in the processes of tissue repair and regeneration, mostly due to the production of soluble bioactive molecules, extracellular vesicles and ECM, which components are predominantly produced within MSC secretome (Kalinina et al, 2015;Keshtkar et al, 2018;Gomez-Salazar et al, 2020). They also include small subpopulation of stem and progenitor cells that can differentiate in adipogenic, osteogenic, chondrogenic, and some other lineages.…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Novoseletskaya

Grigorieva

Nimiritsky

et al. 2020

Front. Cell Dev. Biol.

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Extracellular matrix (ECM) provides both structural support and dynamic microenvironment for cells regulating their behavior and fate. As a critical component of stem cell niche ECM maintains stem cells and activates their proliferation and differentiation under specific stimuli. Mesenchymal stem/stromal cells (MSCs) regulate tissue-specific stem cell functions locating in their immediate microenvironment and producing various bioactive factors, including ECM components. We evaluated the ability of MSC-produced ECM to restore stem and progenitor cell microenvironment in vitro and analyzed the possible mechanisms of its effects. Human MSC cell sheets were decellularized by different agents (detergents, enzymes, and apoptosis inductors) to select the optimized combination (CHAPS and DNAse I) based on the conservation of decellularized ECM (dECM) structure and effectiveness of DNA removal. Prepared dECM was non-immunogenic, supported MSC proliferation and formation of larger colonies in colony-forming unit-assay. Decellularized ECM effectively promoted MSC trilineage differentiation (adipogenic, osteogenic, and chondrogenic) compared to plastic or plastic covered by selected ECM components (collagen, fibronectin, laminin). Interestingly, dECM produced by human fibroblasts could not enhance MSC differentiation like MSC-produced dECM, indicating cell-specific functionality of dECM. We demonstrated the significant integrin contribution in dECM-cell interaction by blocking the stimulatory effects of dECM with RGD peptide and suggested the involvement of key intracellular signaling pathways activation (pERK/ERK and pFAK/FAK axes, pYAP/YAP and beta-catenin) in the observed processes based on the results of inhibitory analysis. Taken together, we suppose that MSC-produced dECM may mimic stem cell niche components in vitro and maintain multipotent progenitor cells to insure their effective response to external differentiating stimuli upon activation. The obtained data provide more insights into the possible role of MSC-produced ECM in stem and progenitor cell regulation within their niches. Our results are also useful for the developing of dECM-based cell-free products for regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Novoseletskaya

Grigorieva

Nimiritsky

et al. 2020

Front. Cell Dev. Biol.

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“…Thus, the physical cues and structural features have gained increasing focus in the field, highlighting their important role in cell differentiation and transplantation ( Figure 1 and Table 1) [105,109]. MSCs were isolated for the first time from BM, and these cells were extensively studied for various applications, as recently reviewed by Gomez-Salazar et al in 2020 [110]. As shown for rat BM-MSCs, human BM-MSCs have the potential to differentiate into the glial lineage and express typical glial markers like S100B, GFAP, p75, and erbB3.…”

Section: Physical-electrical Inductionmentioning

confidence: 99%

“…In Vitro Characterization MSCs were isolated for the first time from BM, and these cells were extensively studied for various applications, as recently reviewed by Gomez-Salazar et al in 2020 [110]. As shown for rat BM-MSCs, human BM-MSCs have the potential to differentiate into the glial lineage and express typical glial markers like S100B, GFAP, p75, and erbB3.…”

Section: Bone Marrow-derived Mscmentioning

confidence: 99%

Schwann Cell-Like Cells: Origin and Usability for Repair and Regeneration of the Peripheral and Central Nervous System

Hopf

Schaefer

Kalbermatten

et al. 2020

Cells

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Functional recovery after neurotmesis, a complete transection of the nerve fiber, is often poor and requires a surgical procedure. Especially for longer gaps (>3 mm), end-to-end suturing of the proximal to the distal part is not possible, thus requiring nerve graft implantation. Artificial nerve grafts, i.e., hollow fibers, hydrogels, chitosan, collagen conduits, and decellularized scaffolds hold promise provided that these structures are populated with Schwann cells (SC) that are widely accepted to promote peripheral and spinal cord regeneration. However, these cells must be collected from the healthy peripheral nerves, resulting in significant time delay for treatment and undesired morbidities for the donors. Therefore, there is a clear need to explore the viable source of cells with a regenerative potential similar to SC. For this, we analyzed the literature for the generation of Schwann cell-like cells (SCLC) from stem cells of different origins (i.e., mesenchymal stem cells, pluripotent stem cells, and genetically programmed somatic cells) and compared their biological performance to promote axonal regeneration. Thus, the present review accounts for current developments in the field of SCLC differentiation, their applications in peripheral and central nervous system injury, and provides insights for future strategies.

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“…"Cell replacement" corresponds to the physiological tissue repair ability through cellular expansion and differentiation upon demand or injuries [2,8]. In contrast, "cell empowerment" is about the influence exerted by MSC on their tissue microenvironment through secretion of soluble bioactive molecules and/or exosomes, which can be dispersed throughout the region [8,75,76].…”

Section: Physiological Properties Of Mscsmentioning

confidence: 99%

Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19

Rocha

Oliveira

Noronha

et al. 2020

Stem Cell Rev and Rep

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Mesenchymal stromal cells (MSCs) constitute a heterogeneous population of stromal cells with immunomodulatory and regenerative properties that support their therapeutic use. MSCs isolated from many tissue sources replicate vigorously in vitro and maintain their main biological properties allowing their widespread clinical application. To date, most MSC-based preclinical and clinical trials targeted immune-mediated and inflammatory diseases. Nevertheless, MSCs have antiviral properties and have been used in the treatment of various viral infections in the last years. Here, we revised in detail the biological properties of MSCs and their preclinical and clinical applications in viral diseases, including the disease caused by the severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) infection (COVID-19). Notably, rapidly increasing numbers of MSC-based therapies for COVID-19 have recently been reported. MSCs are theoretically capable of reducing inflammation and promote lung regeneration in severe COVID-19 patients. We critically discuss the rationale, advantages and disadvantages of MSC-based therapies for viral infections and also specifically for COVID-19 and point out some directions in this field. Finally, we argue that MSC-based therapy may be a promising therapeutic strategy for severe COVID-19 and other emergent respiratory tract viral infections, beyond the viral infection diseases in which MSCs have already been clinically applied.

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Five Decades Later, Are Mesenchymal Stem Cells Still Relevant?

Cited by 121 publications

References 165 publications

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Schwann Cell-Like Cells: Origin and Usability for Repair and Regeneration of the Peripheral and Central Nervous System

Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19

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