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19 pages, 4072 KiB

Open AccessArticle

o-Vanillin Modulates Cell Phenotype and Extracellular Vesicles of Human Mesenchymal Stem Cells and Intervertebral Disc Cells

by Li Li, Kai Sheng, Matthew Mannarino, Peter Jarzem, Hosni Cherif and Lisbet Haglund

Cells 2022, 11(22), 3589; https://doi.org/10.3390/cells11223589 - 13 Nov 2022

Cited by 8 | Viewed by 2281

Abstract

Human mesenchymal stem cell (hMSC) and extracellular vesicle (EV) therapy is a promising treatment for discogenic low back pain (LBP). Although promising, major obstacles remain to be overcome. Cellular senescence reduces self-renewal and multipotent potentials, and the senescence-associated secretory phenotype creates an inflammatory [...] Read more.

Human mesenchymal stem cell (hMSC) and extracellular vesicle (EV) therapy is a promising treatment for discogenic low back pain (LBP). Although promising, major obstacles remain to be overcome. Cellular senescence reduces self-renewal and multipotent potentials, and the senescence-associated secretory phenotype creates an inflammatory environment negatively affecting tissue homeostasis. Reducing senescence could therefore improve regenerative approaches. Ortho-Vanillin (o-Vanillin) has senolytic activity and anti-inflammatory properties and could be a valuable supplement to MSC and EV therapy. Here, we used direct co-culture experiments to evaluate proteoglycan synthesis, inflammatory mediators, and senescent cells in the presence or absence of o-Vanillin. EV release and transfer between hMSCs and intervertebral disc cells (DCs) was examined, and the effect on hMSC differentiation and DC phenotype was evaluated in the presence and absence of o-Vanillin. This study demonstrates that o-Vanillin affects cell communication, enhances hMSC differentiation and improves DC phenotype. Co-cultures of DCs and hMSCs resulted in increased proteoglycan synthesis, a decreased number of senescent cells and decreased release of the cytokines IL6 and 8. Effects that were further enhanced by o-Vanillin. o-Vanillin profoundly increased EV release and/or uptake by hMSCs and DCs. DC markers were significantly upregulated in both cell types in response to conditioned media of o-Vanillin treated donor cells. Collectively, this study demonstrates that o-Vanillin affects hMSC and DC crosstalk and suggests that combining hMSCs and senolytic compounds may improve the outcome of cell supplementation and EV therapy for LBP. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cell-Derived Extracellular Vesicles)

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15 pages, 4520 KiB

Open AccessArticle

Exosomes Derived from Adipose Mesenchymal Stem Cells Promote Diabetic Chronic Wound Healing through SIRT3/SOD2

by Yue Zhang, Xiaozhi Bai, Kuo Shen, Liang Luo, Ming Zhao, Chaolei Xu, Yanhui Jia, Dan Xiao, Yan Li, Xiaowen Gao, Chenyang Tian, Yunchuan Wang and Dahai Hu

Cells 2022, 11(16), 2568; https://doi.org/10.3390/cells11162568 - 18 Aug 2022

Cited by 31 | Viewed by 2827

Abstract

Chronic wounds resulting from diabetes are a major health concern in both industrialized and developing countries, representing one of the leading causes of disability and death. This study aimed to investigate the effect of adipose mesenchymal stem cell-derived exosomes (ADSC-exos) on diabetic wounds [...] Read more.

Chronic wounds resulting from diabetes are a major health concern in both industrialized and developing countries, representing one of the leading causes of disability and death. This study aimed to investigate the effect of adipose mesenchymal stem cell-derived exosomes (ADSC-exos) on diabetic wounds and the mechanism underlying this effect. The results showed that ADSC-exos could improve oxidative stress and secretion of inflammatory cytokines in diabetic wounds, thereby increasing periwound vascularization and accelerating wound healing. At the cellular level, ADSC-exos reduced reactive oxygen species (ROS) generation in human umbilical vein endothelial cells (HUVECs) and improved mitochondrial function in a high-glucose environment. Moreover, the Western blot analysis showed that the high-glucose environment decreased Sirtuin 3 (SIRT3) expression, while exosome treatment increased SIRT3 expression. The activity of superoxide dismutase 2 (SOD2) was enhanced, and the level of inflammatory cytokines was decreased. Further, SIRT3 interference experiments indicated that the effects of ADSC-exos on oxidative stress and angiogenesis were partly dependent on SIRT3. After SIRT3 was inhibited, ROS production increased, while mitochondrial membrane potential and SOD2 activity decreased. These findings confirmed that ADSC-exos could improve the level of high-glucose-induced oxidative stress, promote angiogenesis, and reduce mitochondrial functional impairment and the inflammatory response by regulating SIRT3/SOD2, thus promoting diabetic wound healing. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cell-Derived Extracellular Vesicles)

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18 pages, 4918 KiB

Open AccessArticle

Nano-Sized Extracellular Vesicles Secreted from GATA-4 Modified Mesenchymal Stem Cells Promote Angiogenesis by Delivering Let-7 miRNAs

by Min Gong, Min Wang, Jie Xu, Bin Yu, Yi-Gang Wang, Min Liu, Muhammad Ashraf and Meifeng Xu

Cells 2022, 11(9), 1573; https://doi.org/10.3390/cells11091573 - 07 May 2022

Cited by 9 | Viewed by 2264

Abstract

We demonstrated previously that extracellular vesicles (EVs) released from mesenchymal stem cells (MSCs) play a critical role in angiogenesis. Here, we examine whether this pro-angiogenic efficacy is enhanced in EVs derived from MSCs overexpressing GATA-4 (MSC^GATA−4). Methods and Results. EVs were [...] Read more.

We demonstrated previously that extracellular vesicles (EVs) released from mesenchymal stem cells (MSCs) play a critical role in angiogenesis. Here, we examine whether this pro-angiogenic efficacy is enhanced in EVs derived from MSCs overexpressing GATA-4 (MSC^GATA−4). Methods and Results. EVs were isolated from MSC^GATA-4 (EV^GATA-4) and control MSCs transduced with an empty vector (EV^null). EVs from both cell types were of the same size and displayed similar molecular markers. Compared with EV^null, EV^GATA-4 increased both a tube-like structure formation and spheroid-based sprouting of human umbilical vein endothelial cells (HUVECs). The EV^GATA-4 increased the numbers of CD31-positive cells and hemoglobin content inside Matrigel plugs subcutaneously transplanted into mice for 2 weeks. Moreover, EV^GATA-4 encapsulated higher levels of let-7 family miRs compared to EV^null. The transfer of exosomal let-7 miRs into HUVECs was recorded with an accompanied down-regulation of thrombospondin-1 (THBS1) expression, a major endogenous angiogenesis inhibitor. The loss-and-gain of function studies of let-7 miRs showed that let-7f knockdown significantly decreased EV^GATA-4-mediated vascularization inside Matrigel plugs. In contrast, let-7f overexpression promoted HUVEC migration and tube formation. Conclusion. Our results indicate that EVs derived from genetically modified MSCs with GATA-4 overexpression had increased pro-angiogenic capacity due to the delivery of let-7 miRs that targeted THBS1 in endothelial cells. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cell-Derived Extracellular Vesicles)

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22 pages, 6039 KiB

Open AccessEditor’s ChoiceArticle

Extracellular Vesicles Derived from Primed Mesenchymal Stromal Cells Loaded on Biphasic Calcium Phosphate Biomaterial Exhibit Enhanced Macrophage Polarization

by Neha Rana, Salwa Suliman, Niyaz Al-Sharabi and Kamal Mustafa

Cells 2022, 11(3), 470; https://doi.org/10.3390/cells11030470 - 29 Jan 2022

Cited by 10 | Viewed by 3398

Abstract

Mesenchymal stromal cells (MSC) loaded on biphasic calcium phosphate biomaterial (MSC + BCP) have been used as an advanced therapy medicinal product to treat complex maxillofacial bone defects in patients. Further, MSC-derived extracellular vesicles (EVs) are established vehicles of paracrine factors, supporting inter-cellular [...] Read more.

Mesenchymal stromal cells (MSC) loaded on biphasic calcium phosphate biomaterial (MSC + BCP) have been used as an advanced therapy medicinal product to treat complex maxillofacial bone defects in patients. Further, MSC-derived extracellular vesicles (EVs) are established vehicles of paracrine factors, supporting inter-cellular communication between MSC and other interacting cell types, such as monocytes/macrophages. However, the information about the immunomodulatory potential of EVs derived from MSC and biomaterial constructs (MSC + BCP:EV) and inflammatory primed constructs (MSCp + BCP:EV) are scarce. Hence, we isolated and characterized EVs from these different systems, and compared their cytokine contents with plastic-adherent MSC-derived EVs (MSC:EV). When EVs from all three MSC systems were added to the primary blood-derived macrophages in vitro, significantly higher numbers of M0 (naive) macrophages shifted to M2-like (anti-inflammatory) by MSCp + BCP:EV treatment. Further, this treatment led to enhanced switching of M1 polarized macrophages to M2 polarized, and conversely, M2 to M1, as evaluated by determining the M1/M2 ratios after treatment. The enhanced macrophage modulation by MSCp + BCP:EV was attributed to their higher immunomodulatory (TNFα, IL1β, IL5), angiogenic (VEGF), and chemokine-rich (RANTES, MCP1, MIP1β) cytokine cargo. In conclusion, we successfully isolated and characterized EVs from MSC + BCP constructs and demonstrated that, depending upon the tissue microenvironment, these EVs contribute towards modulating the macrophage-mediated inflammation and healing responses. The study offers new insights into the use of biomaterial-induced EVs for MSC secretome delivery, as a step towards future ‘cell-free’ bone regenerative therapies. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cell-Derived Extracellular Vesicles)

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16 pages, 2502 KiB

Open AccessArticle

Dermal Papilla Cell-Derived Extracellular Vesicles Increase Hair Inductive Gene Expression in Adipose Stem Cells via β-Catenin Activation

by Taheruzzaman Kazi, Abir Nagata, Takatoshi Nakagawa, Takashi Matsuzaki and Shigeki Inui

Cells 2022, 11(2), 202; https://doi.org/10.3390/cells11020202 - 07 Jan 2022

Cited by 12 | Viewed by 3455

Abstract

Recently, extracellular vesicle (EV)-mediated cell differentiation has gained attention in developmental biology due to genetic exchange between donor cells and recipient cells via transfer of mRNA and miRNA. EVs, also known as exosomes, play a role in maintaining paracrine cell communication and can [...] Read more.

Recently, extracellular vesicle (EV)-mediated cell differentiation has gained attention in developmental biology due to genetic exchange between donor cells and recipient cells via transfer of mRNA and miRNA. EVs, also known as exosomes, play a role in maintaining paracrine cell communication and can induce cell proliferation and differentiation. However, it remains unclear whether adipose-derived stem cells (ASCs) can adopt dermal papilla (DP)-like properties with dermal papilla cell-derived extracellular vesicles (DPC-EVs). To understand the effect of DPC-EVs on cell differentiation, DPC-EVs were characterized and incubated with ASCs, of monolayer and spheroid cell cultures, in combination with the CAO1/2FP medium specialized for dermal papilla cells (DPCs). DPC-like properties in ASCs were initially evaluated by comparing several genes and proteins with those of DPCs via real-time PCR analysis and immunostaining, respectively. We also evaluated the presence of hair growth-related microRNAs (miRNAs), specifically mir-214-5P, mir-218-5p, and mir-195-5P. Here, we found that miRNA expression patterns varied in DPC-EVs from passage 4 (P4) or P5. In addition, DPC-EVs in combination with CAP1/2FP accelerated ASC proliferation at low concentrations and propagated hair inductive gene expression for versican (vcan), alpha-smooth muscle actin (α-sma), osteopontin (opn), and N-Cam (ncam). Comparison between the expression of hair inductive genes (vcan, α-sma, ctnb, and others), the protein VCAN, α-SMA and β-Catenin (CTNB), and hair inductive miRNAs (mir-214-5P, mir-218-5p, and mir-195-5p) of DPC-EVs revealed similarities between P4 DPC-EVs-treated ASCs and DPCs. We concluded that early passage DPC-EVs, in combination with CAP1/2FP, enabled ASCs to transdifferentiate into DPC-like cells. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cell-Derived Extracellular Vesicles)

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18 pages, 3575 KiB

Open AccessArticle

Surface Marker Expression in Small and Medium/Large Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Naive or Apoptotic Condition Using Orthogonal Techniques

by Renata Skovronova, Cristina Grange, Veronica Dimuccio, Maria Chiara Deregibus, Giovanni Camussi and Benedetta Bussolati

Cells 2021, 10(11), 2948; https://doi.org/10.3390/cells10112948 - 29 Oct 2021

Cited by 19 | Viewed by 6010

Abstract

Extracellular vesicles released by mesenchymal stromal cells (MSC-EVs) are a promising resource for regenerative medicine. Small MSC-EVs represent the active EV fraction. A bulk analysis was applied to characterise MSC-EVs’ identity and purity, with the assessment of single EV morphology, size and integrity [...] Read more.

Extracellular vesicles released by mesenchymal stromal cells (MSC-EVs) are a promising resource for regenerative medicine. Small MSC-EVs represent the active EV fraction. A bulk analysis was applied to characterise MSC-EVs’ identity and purity, with the assessment of single EV morphology, size and integrity using electron microscopy. We applied different methods to quantitatively analyse the size and surface marker expression in medium/large and small fractions, namely 10k and 100k fractions, of MSC-EVs obtained using sequential ultracentrifugation. Bone marrow, adipose tissue and umbilical cord MSC-EVs were compared in naive and apoptotic conditions. As detected by electron microscopy, the 100k EV size < 100 nm was confirmed by super-resolution microscopy and ExoView. Single-vesicle imaging using super-resolution microscopy revealed heterogeneous patterns of tetraspanins. ExoView allowed a comparative screening of single MSC-EV tetraspanin and mesenchymal markers. A semiquantitative bead-based cytofluorimetric analysis showed the segregation of immunological and pro-coagulative markers on the 10k MSC-EVs. Apoptotic MSC-EVs were released in higher numbers, without significant differences in the naive fractions in surface marker expression. These results show a consistent profile of MSC-EV fractions among the different sources and a safer profile of the 100k MSC-EV population for clinical application. Our study identified suitable applications for EV analytical techniques. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cell-Derived Extracellular Vesicles)

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18 pages, 5142 KiB

Open AccessArticle

Lung Fibrosis Is Improved by Extracellular Vesicles from IFNγ-Primed Mesenchymal Stromal Cells in Murine Systemic Sclerosis

by Pauline Rozier, Marie Maumus, Alexandre Thibault Jacques Maria, Karine Toupet, Christian Jorgensen, Philippe Guilpain and Danièle Noël

Cells 2021, 10(10), 2727; https://doi.org/10.3390/cells10102727 - 13 Oct 2021

Cited by 14 | Viewed by 2498

Abstract

Background: Systemic sclerosis (SSc) is a severe autoimmune disease for which mesenchymal stromal cells (MSCs)-based therapy was reported to reduce SSc-related symptoms in pre-clinical studies. Recently, extracellular vesicles released by MSCs (MSC-EVs) were shown to mediate most of their therapeutic effect. Here, we [...] Read more.

Background: Systemic sclerosis (SSc) is a severe autoimmune disease for which mesenchymal stromal cells (MSCs)-based therapy was reported to reduce SSc-related symptoms in pre-clinical studies. Recently, extracellular vesicles released by MSCs (MSC-EVs) were shown to mediate most of their therapeutic effect. Here, we aimed at improving their efficacy by increasing the MSC-EV dose or by IFNγ-priming of MSCs. Methods: small size (ssEVs) and large size EVs (lsEVs) were recovered from murine MSCs that were pre-activated using 1 or 20 ng/mL of IFNγ. In the HOCl-induced model of SSc, mice were treated with EVs at day 21 and sacrificed at day 42. Lung and skin samples were collected for histological and molecular analyses. Results: increasing the dose of MSC-EVs did not add benefit to the dose previously reported to be efficient in SSc. By contrast, IFNγ pre-activation improved MSC-EVs-based treatment, essentially in the lungs. Low doses of IFNγ decreased the expression of fibrotic markers, while high doses improved remodeling and anti-inflammatory markers. IFNγ pre-activation upregulated iNos, IL1ra and Il6 in MSCs and ssEVs and the PGE2 protein in lsEVs. Conclusion: IFNγ-pre-activation improved the therapeutic effect of MSC-EVs preferentially in the lungs of SSc mice by modulating anti-inflammatory and anti-fibrotic markers. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cell-Derived Extracellular Vesicles)

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22 pages, 2695 KiB

Open AccessArticle

Potential Therapeutic Effect of Micrornas in Extracellular Vesicles from Mesenchymal Stem Cells against SARS-CoV-2

by Jae Hyun Park, Yuri Choi, Chul-Woo Lim, Ji-Min Park, Shin-Hye Yu, Yujin Kim, Hae Jung Han, Chun-Hyung Kim, Young-Sook Song, Chul Kim, Seung Rok Yu, Eun Young Oh, Sang-Myeong Lee and Jisook Moon

Cells 2021, 10(9), 2393; https://doi.org/10.3390/cells10092393 - 12 Sep 2021

Cited by 29 | Viewed by 3592

Abstract

Extracellular vesicles (EVs) are cell-released, nanometer-scaled, membrane-bound materials and contain diverse contents including proteins, small peptides, and nucleic acids. Once released, EVs can alter the microenvironment and regulate a myriad of cellular physiology components, including cell–cell communication, proliferation, differentiation, and immune responses against [...] Read more.

Extracellular vesicles (EVs) are cell-released, nanometer-scaled, membrane-bound materials and contain diverse contents including proteins, small peptides, and nucleic acids. Once released, EVs can alter the microenvironment and regulate a myriad of cellular physiology components, including cell–cell communication, proliferation, differentiation, and immune responses against viral infection. Among the cargoes in the vesicles, small non-coding micro-RNAs (miRNAs) have received attention in that they can regulate the expression of a variety of human genes as well as external viral genes via binding to the complementary mRNAs. In this study, we tested the potential of EVs as therapeutic agents for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. First, we found that the mesenchymal stem-cell-derived EVs (MSC-EVs) enabled the rescue of the cytopathic effect of SARS-CoV-2 virus and the suppression of proinflammatory responses in the infected cells by inhibiting the viral replication. We found that these anti-viral responses were mediated by 17 miRNAs matching the rarely mutated, conserved 3′-untranslated regions (UTR) of the viral genome. The top five miRNAs highly expressed in the MSC-EVs, miR-92a-3p, miR-26a-5p, miR-23a-3p, miR-103a-3p, and miR-181a-5p, were tested. They were bound to the complemented sequence which led to the recovery of the cytopathic effects. These findings suggest that the MSC-EVs are a potential candidate for multiple variants of anti-SARS-CoV-2. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cell-Derived Extracellular Vesicles)

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17 pages, 7621 KiB

Open AccessArticle

Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors

by Kyung-Ah Cho, Da-Won Choi, Yu-Hee Kim, Jungwoo Kim, Kyung-Ha Ryu and So-Youn Woo

Cells 2021, 10(8), 2169; https://doi.org/10.3390/cells10082169 - 23 Aug 2021

Cited by 14 | Viewed by 3011

Abstract

Skeletal muscle mass is decreased under a wide range of pathologic conditions. In particular, chemotherapy is well known for inducing muscle loss and atrophy. Previous studies using tonsil-derived mesenchymal stem cells (T-MSCs) or a T-MSC-conditioned medium showed effective recovery of total body weight [...] Read more.

Skeletal muscle mass is decreased under a wide range of pathologic conditions. In particular, chemotherapy is well known for inducing muscle loss and atrophy. Previous studies using tonsil-derived mesenchymal stem cells (T-MSCs) or a T-MSC-conditioned medium showed effective recovery of total body weight in the chemotherapy-preconditioned bone marrow transplantation mouse model. This study investigated whether extracellular vesicles of T-MSCs, such as exosomes, are a key player in the recovery of body weight and skeletal muscle mass in chemotherapy-treated mice. T-MSC exosomes transplantation significantly decreased loss of total body weight and muscle mass in the busulfan-cyclophosphamide conditioning regimen in BALB/c recipient mice containing elevated serum activin A. Additionally, T-MSC exosomes rescued impaired C2C12 cell differentiation in the presence of activin A in vitro. We found that T-MSC exosomes possess abundant miR-145-5p, which targets activin A receptors, ACVR2A, and ACVR1B. Indeed, T-MSC exosomes rescue muscle atrophy both in vivo and in vitro via miR-145-5p dependent manner. These results suggest that T-MSC exosomes have therapeutic potential to maintain or improve skeletal muscle mass in various activin A elevated pathologic conditions. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cell-Derived Extracellular Vesicles)

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Review

Jump to: Research

27 pages, 3449 KiB

Open AccessEditor’s ChoiceReview

Mesenchymal Stem Cell-Derived Extracellular Vesicles for Therapeutic Use and in Bioengineering Applications

by Caroline McLaughlin, Pallab Datta, Yogendra P. Singh, Alexis Lo, Summer Horchler, Irina A. Elcheva, Ibrahim T. Ozbolat, Dino J. Ravnic and Srinivas V. Koduru

Cells 2022, 11(21), 3366; https://doi.org/10.3390/cells11213366 - 25 Oct 2022

Cited by 9 | Viewed by 2836

Abstract

Extracellular vesicles (EVs) are small lipid bilayer-delimited particles that are naturally released from cells into body fluids, and therefore can travel and convey regulatory functions in the distal parts of the body. EVs can transmit paracrine signaling by carrying over cytokines, chemokines, growth [...] Read more.

Extracellular vesicles (EVs) are small lipid bilayer-delimited particles that are naturally released from cells into body fluids, and therefore can travel and convey regulatory functions in the distal parts of the body. EVs can transmit paracrine signaling by carrying over cytokines, chemokines, growth factors, interleukins (ILs), transcription factors, and nucleic acids such as DNA, mRNAs, microRNAs, piRNAs, lncRNAs, sn/snoRNAs, mtRNAs and circRNAs; these EVs travel to predecided destinations to perform their functions. While mesenchymal stem cells (MSCs) have been shown to improve healing and facilitate treatments of various diseases, the allogenic use of these cells is often accompanied by serious adverse effects after transplantation. MSC-produced EVs are less immunogenic and can serve as an alternative to cellular therapies by transmitting signaling or delivering biomaterials to diseased areas of the body. This review article is focused on understanding the properties of EVs derived from different types of MSCs and MSC–EV-based therapeutic options. The potential of modern technologies such as 3D bioprinting to advance EV-based therapies is also discussed. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cell-Derived Extracellular Vesicles)

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31 pages, 930 KiB

Open AccessReview

Biomaterials and Extracellular Vesicle Delivery: Current Status, Applications and Challenges

by Kasey S. Leung, Sajjad Shirazi, Lyndon F. Cooper and Sriram Ravindran

Cells 2022, 11(18), 2851; https://doi.org/10.3390/cells11182851 - 13 Sep 2022

Cited by 9 | Viewed by 3968

Abstract

In this review, we will discuss the current status of extracellular vesicle (EV) delivery via biopolymeric scaffolds for therapeutic applications and the challenges associated with the development of these functionalized scaffolds. EVs are cell-derived membranous structures and are involved in many physiological processes. [...] Read more.

In this review, we will discuss the current status of extracellular vesicle (EV) delivery via biopolymeric scaffolds for therapeutic applications and the challenges associated with the development of these functionalized scaffolds. EVs are cell-derived membranous structures and are involved in many physiological processes. Naïve and engineered EVs have much therapeutic potential, but proper delivery systems are required to prevent non-specific and off-target effects. Targeted and site-specific delivery using polymeric scaffolds can address these limitations. EV delivery with scaffolds has shown improvements in tissue remodeling, wound healing, bone healing, immunomodulation, and vascular performance. Thus, EV delivery via biopolymeric scaffolds is becoming an increasingly popular approach to tissue engineering. Although there are many types of natural and synthetic biopolymers, the overarching goal for many tissue engineers is to utilize biopolymers to restore defects and function as well as support host regeneration. Functionalizing biopolymers by incorporating EVs works toward this goal. Throughout this review, we will characterize extracellular vesicles, examine various biopolymers as a vehicle for EV delivery for therapeutic purposes, potential mechanisms by which EVs exert their effects, EV delivery for tissue repair and immunomodulation, and the challenges associated with the use of EVs in scaffolds. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cell-Derived Extracellular Vesicles)

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20 pages, 1628 KiB

Open AccessReview

Potential Cell-Based and Cell-Free Therapy for Patients with COVID-19

by Marselina Irasonia Tan, Nayla Majeda Alfarafisa, Popi Septiani, Anggraini Barlian, Mochamad Firmansyah, Ahmad Faizal, Lili Melani and Husna Nugrahapraja

Cells 2022, 11(15), 2319; https://doi.org/10.3390/cells11152319 - 27 Jul 2022

Cited by 9 | Viewed by 2781

Abstract

Since it was first reported, the novel coronavirus disease 2019 (COVID-19) remains an unresolved puzzle for biomedical researchers in different fields. Various treatments, drugs, and interventions were explored as treatments for COVID. Nevertheless, there are no standard and effective therapeutic measures. Meanwhile, mesenchymal [...] Read more.

Since it was first reported, the novel coronavirus disease 2019 (COVID-19) remains an unresolved puzzle for biomedical researchers in different fields. Various treatments, drugs, and interventions were explored as treatments for COVID. Nevertheless, there are no standard and effective therapeutic measures. Meanwhile, mesenchymal stem cell (MSC) therapy offers a new approach with minimal side effects. MSCs and MSC-based products possess several biological properties that potentially alleviate COVID-19 symptoms. Generally, there are three classifications of stem cell therapy: cell-based therapy, tissue engineering, and cell-free therapy. This review discusses the MSC-based and cell-free therapies for patients with COVID-19, their potential mechanisms of action, and clinical trials related to these therapies. Cell-based therapies involve the direct use and injection of MSCs into the target tissue or organ. On the other hand, cell-free therapy uses secreted products from cells as the primary material. Cell-free therapy materials can comprise cell secretomes and extracellular vesicles. Each therapeutic approach possesses different benefits and various risks. A better understanding of MSC-based and cell-free therapies is essential for supporting the development of safe and effective COVID-19 therapy. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cell-Derived Extracellular Vesicles)

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