Mesenchymal stem cells are prospective novel off-the-shelf wound management tools

Malhotra, Poonam; Shukla, Manish; Meena, Poonam; Kakkar, Anupama; Khatri, Nitin; Nagar, Rakesh Kumar; Kumar, Mahesh; Saraswat, Sumit Kumar; Shrivastava, Supriya; Datt, Rajan; Pandey, Siddharth

doi:10.1007/s13346-021-00925-6

Cited by 12 publications

(12 citation statements)

References 126 publications

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“…Since MIF acts as an upstream regulator of multiple cytokines ( Calandra and Roger, 2003 ), we investigated the secretion profile of IL-6, IL-1β, and TNF-α, which have been shown to be secreted by MSCs ( Paquet et al, 2015 ; Antebi et al, 2018 ) and to be downstream of MIF ( Calandra and Roger, 2003 ). The profile of soluble factors released by MSCs is profoundly influenced by sex, age, species, underlying disease conditions and environmental factors like hypoxia or other cytokine stimuli ( Malhotra et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

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The Role of Macrophage Migration Inhibitory Factor in Adipose-Derived Stem Cells Under Hypoxia

et al. 2021

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Background: Adipose-derived stem cells (ASCs) are multipotent mesenchymal stem cells characterized by their strong regenerative potential and low oxygen consumption. Macrophage migration inhibitory factor (MIF) is a multifunctional chemokine-like cytokine that is involved in tissue hypoxia. MIF is not only a major immunomodulator but also is highly expressed in adipose tissue such as subcutaneous adipose tissue of chronic non-healing wounds. In the present study, we investigated the effect of hypoxia on MIF in ASCs isolated from healthy versus inflamed adipose tissue.Methods: Human ASCs were harvested from 17 patients (11 healthy adipose tissue samples, six specimens from chronic non-healing wounds). ASCs were treated in a hypoxia chamber at <1% oxygen. ASC viability, MIF secretion as well as expression levels of MIF, its receptor CD74, hypoxia-inducible transcription factor-1α (HIF-1α) and activation of the AKT and ERK signaling pathways were analyzed. The effect of recombinant MIF on the viability of ASCs was determined. Finally, the effect of MIF on the viability and production capacity of ASCs to produce the inflammatory cytokines tumor necrosis factor (TNF), interleukin (IL)-6, and IL-1β was determined upon treatment with recombinant MIF and/or a blocking MIF antibody.Results: Hypoxic treatment inhibited proliferation of ASCs derived from healthy or chronic non-healing wounds. ASCs from healthy adipose tissue samples were characterized by a low degree of MIF secretion during hypoxic challenge. In contrast, in ASCs from adipose tissue samples of chronic non-healing wounds, secretion and expression of MIF and CD74 expression were significantly elevated under hypoxia. This was accompanied by enhanced ERK signaling, while AKT signaling was not altered. Recombinant MIF did stimulate HIF-1α expression under hypoxia as well as AKT and ERK phosphorylation, while no effect on ASC viability was observed. Recombinant MIF significantly reduced the secretion of IL-1β under hypoxia and normoxia, and neutralizing MIF-antibodies diminished TNF-α and IL-1β release in hypoxic ASCs.Conclusions: Collectively, MIF did not affect the viability of ASCs from neither healthy donor site nor chronic wounds. Our results, however, suggest that MIF has an impact on the wound environment by modulating inflammatory factors such as IL-1β.

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Section: Discussionmentioning

confidence: 99%

“…Previous studies reported that MSCs secrete TNF-α and IL-1β ( Harrell et al, 2019 ) and that their paracrine action is involved in immunomodulatory effects ( Malhotra et al, 2021 ). Furthermore, TNF-α and IL-1β are commonly used to precondition of MSCs and ASCs as they profoundly modulate their secretome ( Lee et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

The Role of Macrophage Migration Inhibitory Factor in Adipose-Derived Stem Cells Under Hypoxia

et al. 2021

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“…Criteria for isolation, culture, and identification of MSCs have been established by the International Society for Cellular Therapy (ISCT) ( Galderisi and Giordano, 2014 ). The biological roles of MSCs in skin regeneration and repair have been reported widely ( Kosaric et al, 2019 ; Zhang et al, 2020 ; Malhotra et al, 2021 ). Collectively, the biological roles of MSCs include controlling excessive immune response in skin wounds for their immunomodulatory capacity ( Uchiyama et al, 2017 ), secreting paracrine factors such as EVs to contribute to the healing process ( Qi et al, 2014 ; Bian et al, 2020 ), and differentiating into skin repair cells for their multiple differentiation potential ( Zhang et al, 2020 ).…”

Section: Biological Characteristics and Clinical Applications Of Mscsmentioning

confidence: 99%

Small extracellular vesicles from mesenchymal stem cells: A potential Weapon for chronic non-healing wound treatment

Wei

Liu

et al. 2023

Front. Bioeng. Biotechnol.

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Chronic non-healing wounds have posed a severe threat to patients mentally and physically. Behavior dysregulation of remaining cells at wound sites is recognized as the chief culprit to destroy healing process and hinders wound healing. Therefore, regulating and restoring normal cellular behavior is the core of chronic non-healing wound treatment. In recent years, the therapy with mesenchymal stem cells (MSCs) has become a promising option for chronic wound healing and the efficacy has increasingly been attributed to their exocrine functions. Small extracellular vesicles derived from MSCs (MSC-sEVs) are reported to benefit almost all stages of wound healing by regulating the cellular behavior to participate in the process of inflammatory response, angiogenesis, re-epithelization, and scarless healing. Here, we describe the characteristics of MSC-sEVs and discuss their therapeutic potential in chronic wound treatment. Additionally, we also provide an overview of the application avenues of MSC-sEVs in wound treatment. Finally, we summarize strategies for large-scale production and engineering of MSC-sEVs. This review may possibly provide meaningful guidance for chronic wound treatment with MSC-sEVs.

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“…The clinical utility of BM-MSCs is enhanced by the ability to use allogeneic cells. MSCs exert an array of beneficial effects through each phase of the wound healing process [20,21]. Clinical trials have demonstrated that autologous and allogeneic MSC therapy aids in chronic wound closure [22][23][24][25][26][27][28][29][30].…”

Section: Lessons Learned From Mesenchymal Stem Cellsmentioning

confidence: 99%

Extracellular Vesicles as Therapeutic Tools for the Treatment of Chronic Wounds

et al. 2021

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Chronic wounds develop when the orderly process of cutaneous wound healing is delayed or disrupted. Development of a chronic wound is associated with significant morbidity and financial burden to the individual and health-care system. Therefore, new therapeutic modalities are needed to address this serious condition. Mesenchymal stem cells (MSCs) promote skin repair, but their clinical use has been limited due to technical challenges. Extracellular vesicles (EVs) are particles released by cells that carry bioactive molecules (lipids, proteins, and nucleic acids) and regulate intercellular communication. EVs (exosomes, microvesicles, and apoptotic bodies) mediate key therapeutic effects of MSCs. In this review we examine the experimental data establishing a role for EVs in wound healing. Then, we explore techniques for designing EVs to function as a targeted drug delivery system and how EVs can be incorporated into biomaterials to produce a personalized wound dressing. Finally, we discuss the status of clinically deploying EVs as a therapeutic agent in wound care.

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Mesenchymal stem cells are prospective novel off-the-shelf wound management tools

Cited by 12 publications

References 126 publications

The Role of Macrophage Migration Inhibitory Factor in Adipose-Derived Stem Cells Under Hypoxia

The Role of Macrophage Migration Inhibitory Factor in Adipose-Derived Stem Cells Under Hypoxia

Small extracellular vesicles from mesenchymal stem cells: A potential Weapon for chronic non-healing wound treatment

Extracellular Vesicles as Therapeutic Tools for the Treatment of Chronic Wounds

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