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14 pages, 5736 KiB

Open AccessArticle

Conducting Polymer Mediated Electrical Stimulation Induces Multilineage Differentiation with Robust Neuronal Fate Determination of Human Induced Pluripotent Stem Cells

by Eva Tomaskovic-Crook, Qi Gu, Siti N Abdul Rahim, Gordon G Wallace and Jeremy M Crook

Cells 2020, 9(3), 658; https://doi.org/10.3390/cells9030658 - 9 Mar 2020

Cited by 25 | Viewed by 4968

Abstract

Electrical stimulation is increasingly being used to modulate human cell behaviour for biotechnological research and therapeutics. Electrically conductive polymers (CPs) such as polypyrrole (PPy) are amenable to in vitro and in vivo cell stimulation, being easy to synthesise with different counter ions (dopants) [...] Read more.

Electrical stimulation is increasingly being used to modulate human cell behaviour for biotechnological research and therapeutics. Electrically conductive polymers (CPs) such as polypyrrole (PPy) are amenable to in vitro and in vivo cell stimulation, being easy to synthesise with different counter ions (dopants) to augment biocompatibility and cell-effects. Extending our earlier work, which showed that CP-mediated electrical stimulation promotes human neural stem cell differentiation, here we report using electroactive PPy containing the anionic dopant dodecylbenzenesulfonate (DBS) to modulate the fate determination of human induced pluripotent stem cells (iPSCs). Remarkably, the stimulation without conventional chemical inducers resulted in the iPSCs differentiating to cells of the three germ lineages—endoderm, ectoderm, and mesoderm. The unstimulated iPSC controls remained undifferentiated. Phenotypic characterisation further showed a robust induction to neuronal fate with electrical stimulation, again without customary chemical inducers. Our findings add to the growing body of evidence supporting the use of electrical stimulation to augment stem cell differentiation, more specifically, pluripotent stem cell differentiation, and especially neuronal induction. Moreover, we have shown the versatility of electroactive PPy as a cell-compatible platform for advanced stem cell research and translation, including identifying novel mechanisms of fate regulation, tissue development, electroceuticals, and regenerative medicine. Full article

(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)

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18 pages, 4855 KiB

Open AccessArticle

Cytokine Directed Chondroblast Trans-Differentiation: JAK Inhibition Facilitates Direct Reprogramming of Fibroblasts to Chondroblasts

by Perla Cota, Summer A. Helmi, Charlie Hsu and Derrick E. Rancourt

Cells 2020, 9(1), 191; https://doi.org/10.3390/cells9010191 - 11 Jan 2020

Cited by 7 | Viewed by 5446

Abstract

Osteoarthritis (OA) is a degenerative disease of the hyaline articular cartilage. This disease is progressive and may lead to disability. Researchers proposed many regenerative approaches to treat osteoarthritis, including stem cells. Trans-differentiation of a fully differentiated cell state directly into another different differentiated [...] Read more.

Osteoarthritis (OA) is a degenerative disease of the hyaline articular cartilage. This disease is progressive and may lead to disability. Researchers proposed many regenerative approaches to treat osteoarthritis, including stem cells. Trans-differentiation of a fully differentiated cell state directly into another different differentiated cell state avoids the disadvantages of fully reprogramming cells to induced pluripotent stem cells (iPSCs) in terms of faster reprogramming of the needed cells. Trans-differentiation also reduces the risk of tumor formation by avoiding the iPSC state. OSKM factors (Oct4, Sox2, Klf4, and cMyc) accompanied by the JAK-STAT pathway inhibition, followed by the introduction of specific differentiation factors, directly reprogrammed mouse embryonic fibroblasts to chondroblasts. Our results showed the absence of intermediate induced pluripotent stem cell formation. The resulting aggregates showed clear hyaline and hypertrophic cartilage. Tumor formation was absent in sub-cutaneous capsules transplanted in SCID mice. Full article

(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)

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16 pages, 4497 KiB

Open AccessArticle

Enhanced Host Neovascularization of Prevascularized Engineered Muscle Following Transplantation into Immunocompetent versus Immunocompromised Mice

by Luba Perry, Uri Merdler, Maria Elishaev and Shulamit Levenberg

Cells 2019, 8(12), 1472; https://doi.org/10.3390/cells8121472 - 20 Nov 2019

Cited by 16 | Viewed by 3125

Abstract

Engineering of functional tissue, by combining either autologous or allogeneic cells with biomaterials, holds promise for the treatment of various diseases and injuries. Prevascularization of the engineered tissue was shown to enhance and improve graft integration and neovascularization post-implantation in immunocompromised mice. However, [...] Read more.

Engineering of functional tissue, by combining either autologous or allogeneic cells with biomaterials, holds promise for the treatment of various diseases and injuries. Prevascularization of the engineered tissue was shown to enhance and improve graft integration and neovascularization post-implantation in immunocompromised mice. However, the neovascularization and integration processes of transplanted engineered tissues have not been widely studied in immunocompetent models. Here, we fabricated a three-dimensional (3D) vascularized murine muscle construct that was transplanted into immunocompetent and immunocompromised mice. Intravital imaging demonstrated enhanced neovascularization in immunocompetent mice compared to immunocompromised mice, 18 days post-implantation, indicating the advantageous effect of an intact immune system on neovascularization. Moreover, construct prevascularization enhanced neovascularization, integration, and myogenesis in both animal models. These findings demonstrate the superiority of implantation into immunocompetent over immunocompromised mice and, therefore, suggest that using autologous cells might be beneficial compared to allogeneic cells and subsequent immunosuppression. Taken together, these observations have the potential to advance the field of regenerative medicine and tissue engineering, ultimately reducing the need for donor organs and tissues. Full article

(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)

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19 pages, 21756 KiB

Open AccessArticle

MiR-21, MiR-29a, GATA4, and MEF2c Expression Changes in Endothelin-1 and Angiotensin II Cardiac Hypertrophy Stimulated Isl-1⁺Sca-1⁺c-kit⁺ Porcine Cardiac Progenitor Cells In Vitro

by Katrin Zlabinger, Andreas Spannbauer, Denise Traxler, Alfred Gugerell, Dominika Lukovic, Johannes Winkler, Julia Mester-Tonczar, Bruno Podesser and Mariann Gyöngyösi

Cells 2019, 8(11), 1416; https://doi.org/10.3390/cells8111416 - 9 Nov 2019

Cited by 12 | Viewed by 4192

Abstract

Cost- and time-intensive porcine translational disease models offer great opportunities to test drugs and therapies for pathological cardiac hypertrophy and can be supported by porcine cell culture models that provide further insights into basic disease mechanisms. Cardiac progenitor cells (CPCs) residing in the [...] Read more.

Cost- and time-intensive porcine translational disease models offer great opportunities to test drugs and therapies for pathological cardiac hypertrophy and can be supported by porcine cell culture models that provide further insights into basic disease mechanisms. Cardiac progenitor cells (CPCs) residing in the adult heart have been shown to differentiate in vitro into cardiomyocytes and could contribute to cardiac regeneration. Therefore, it is important to evaluate their changes on the cellular level caused by disease. We successfully isolated Isl1⁺Sca1⁺cKit⁺ porcine CPCs (pCPCs) from pig hearts and stimulated them with endothelin-1 (ET-1) and angiotensin II (Ang II) in vitro. We also performed a cardiac reprogramming transfection and tested the same conditions. Our results show that undifferentiated Isl1⁺Sca1⁺cKit⁺ pCPCs were significantly upregulated in GATA4, MEF2c, and miR-29a gene expressions and in BNP and MCP-1 protein expressions with Ang II stimulation, but they showed no significant changes in miR-29a and MCP-1 when stimulated with ET-1. Differentiated Isl1⁺Sca1⁺cKit⁺ pCPCs exhibited significantly higher levels of MEF2c, GATA4, miR-29a, and miR-21 as well as Cx43 and BNP with Ang II stimulation. pMx-MGT-transfected Isl1⁺Sca1⁺cKit⁺ pCPCs showed significant elevations in MEF2c, GATA4, and BNP expressions when stimulated with ET-1. Our model demonstrates that in vitro stimulation leads to successful Isl1⁺Sca1⁺cKit⁺ pCPC hypertrophy with upregulation of cardiac remodeling associated genes and profibrotic miRNAs and offers great possibilities for further investigations of disease mechanisms and treatment. Full article

(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)

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20 pages, 21316 KiB

Open AccessArticle

by Eleonora Mazzotti, Gabriella Teti, Mirella Falconi, Francesca Chiarini, Barbara Barboni, Antonio Mazzotti and Aurelio Muttini

Cells 2019, 8(10), 1116; https://doi.org/10.3390/cells8101116 - 20 Sep 2019

Cited by 17 | Viewed by 3794

Abstract

Osteoarthritis is a degenerative disease that strongly correlates with age and promotes the breakdown of joint cartilage and subchondral bone. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stromal cells (MSCs) isolated from [...] Read more.

Osteoarthritis is a degenerative disease that strongly correlates with age and promotes the breakdown of joint cartilage and subchondral bone. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stromal cells (MSCs) isolated from adult tissues. It seems that MSCs derived from synovial joint tissues exhibit superior chondrogenic ability, but their unclear distribution and low frequency actually limit their clinical application. To date, the influence of aging on synovial joint derived MSCs’ biological characteristics and differentiation abilities remains unknown, and a full understanding of the mechanisms involved in cellular aging is lacking. The aim of this study was therefore to investigate the presence of age-related alterations in synovial fluid MSCs and their influence on the potential ability of MSCs to differentiate toward chondrogenic phenotypes. Synovial fluid MSCs, isolated from healthy equine donors from 3 to 40 years old, were cultured in vitro and stimulated towards chondrogenic differentiation for up to 21 days. An equine model was chosen due to the high degree of similarity of the anatomy of the knee joint to the human knee joint and as spontaneous disorders develop that are clinically relevant to similar human disorders. The results showed a reduction in cell proliferation correlated with age and the presence of age-related tetraploid cells. Ultrastructural analysis demonstrated the presence of morphological features correlated with aging such as endoplasmic reticulum stress, autophagy, and mitophagy. Alcian blue assay and real-time PCR data showed a reduction of efficiency in the chondrogenic differentiation of aged synovial fluid MSCs compared to young MSCs. All these data highlighted the influence of aging on MSCs’ characteristics and ability to differentiate towards chondrogenic differentiation and emphasize the importance of considering age-related alterations of MSCs in clinical applications. Full article

(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)

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18 pages, 5557 KiB

Open AccessArticle

mRNA-Driven Generation of Transgene-Free Neural Stem Cells from Human Urine-Derived Cells

by Phil Jun Kang, Daryeon Son, Tae Hee Ko, Wonjun Hong, Wonjin Yun, Jihoon Jang, Jong-Il Choi, Gwonhwa Song, Jangbo Lee, In Yong Kim and Seungkwon You

Cells 2019, 8(9), 1043; https://doi.org/10.3390/cells8091043 - 6 Sep 2019

Cited by 9 | Viewed by 4784

Abstract

Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated [...] Read more.

Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated transgenes in the host genome, contributing to the risk for undesired genotoxicity and tumorigenesis. Here, we describe the advanced transgene-free generation of iNSCs from human urine-derived cells (HUCs) by combining a cocktail of defined small molecules with self-replicable mRNA delivery. The established iNSCs were completely transgene-free in their cytosol and genome and further resembled human embryonic stem cell-derived NSCs in the morphology, biological characteristics, global gene expression, and potential to differentiate into functional neurons, astrocytes, and oligodendrocytes. Moreover, iNSC colonies were observed within eight days under optimized conditions, and no teratomas formed in vivo, implying the absence of pluripotent cells. This study proposes an approach to generate transplantable iNSCs that can be broadly applied for neurological disorders in a safe, efficient, and patient-specific manner. Full article

(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)

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18 pages, 2604 KiB

Open AccessFeature PaperArticle

Efficacy of 3D Culture Priming is Maintained in Human Mesenchymal Stem Cells after Extensive Expansion of the Cells

by Thomas J. Bartosh and Joni H. Ylostalo

Cells 2019, 8(9), 1031; https://doi.org/10.3390/cells8091031 - 5 Sep 2019

Cited by 18 | Viewed by 3963

Abstract

The use of non-optimal preparations of mesenchymal stem cells (MSCs), such as extensively expanded cells, might be necessary to obtain the large numbers of cells needed for many clinical applications. We previously demonstrated that minimally expanded (early passage) MSCs can be pre-activated as [...] Read more.

The use of non-optimal preparations of mesenchymal stem cells (MSCs), such as extensively expanded cells, might be necessary to obtain the large numbers of cells needed for many clinical applications. We previously demonstrated that minimally expanded (early passage) MSCs can be pre-activated as spheroids to produce potentially therapeutic factors in 3D cultures. Here, we used extensively expanded (late passage) MSCs and studied their 3D-culture activation potential. MSCs were culture-expanded as 2D monolayers, and cells from various passages were activated by 3D culture in hanging drops with either fetal bovine serum (FBS)-containing media or a more clinically-applicable animal product-free (xeno-free) media. Gene expression analyses demonstrated that MSC spheroids prepared from passage 3, 5, and 7 cells were similar to each other but different from 2D MSCs. Furthermore, the expression of notable anti-inflammatory/immune-modulatory factors cyclooxygenase-2 (PTGS2), TNF alpha induced protein 6 (TNFAIP6), and stanniocalcin 1 (STC-1) were up-regulated in all spheroid preparations. This was confirmed by the detection of secreted prostaglandin E2 (PGE-2), tumor necrosis factor-stimulated gene 6 (TSG-6, and STC-1. This study demonstrated that extensively expanded MSCs can be activated in 3D culture through spheroid formation in both FBS-containing and xeno-free media. This work highlights the possibility of activating otherwise less useable MSC preparations through 3D culture generating large numbers of potentially therapeutic MSCs. Full article

(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)

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16 pages, 40097 KiB

Open AccessArticle

Combination Therapy of Mesenchymal Stromal Cells and Interleukin-4 Attenuates Rheumatoid Arthritis in a Collagen-Induced Murine Model

by Shaimaa M. Haikal, Nourtan F. Abdeltawab, Laila A. Rashed, Tarek I. Abd El-Galil, Heba A. Elmalt and Magdy A. Amin

Cells 2019, 8(8), 823; https://doi.org/10.3390/cells8080823 - 3 Aug 2019

Cited by 49 | Viewed by 6118

Abstract

Rheumatoid arthritis (RA) is a disease of the joints that causes decreased quality of life. Mesenchymal stromal cells (MSCs) have immunosuppressive properties, with possible use in the treatment of RA. Similarly, interleukin (IL)-4 has been shown as a potential RA treatment. However, their [...] Read more.

Rheumatoid arthritis (RA) is a disease of the joints that causes decreased quality of life. Mesenchymal stromal cells (MSCs) have immunosuppressive properties, with possible use in the treatment of RA. Similarly, interleukin (IL)-4 has been shown as a potential RA treatment. However, their combination has not been explored before. Therefore, this study aimed to investigate the effect of a combination therapy of MSCs and IL-4 in the treatment of RA, using a murine collagen-induced arthritis (CIA) model. Arthritis was induced in Balb/c mice by two intradermal injections of type II collagen (CII), at days 0 and 21. CIA mice were randomly assigned to four groups; group I received an intravenous injection of mouse bone marrow-derived MSCs, while group II received an intraperitoneal injection of IL-4. Group III received a combined treatment of MSC and IL-4, while group IV served as a CIA diseased control group receiving phosphate buffer saline (PBS). A fifth group of healthy mice served as the normal healthy control. To assess changes induced by different treatments, levels of RA-associated inflammatory cytokines and biomarkers were measured in the serum, knee joints, and synovial tissue, using ELISA and Real Time-qPCR. Histopathological features of knee joints were analyzed for all groups. Results showed that combined MSC and IL-4 treatment alleviated signs of synovitis in CIA mice, reverting to the values of healthy controls. This was evident by the decrease in the levels of rheumatic factor (RF), C-reactive protein (CRP) and anti-nuclear antibodies (ANA) by 64, 80, and 71%, respectively, compared to the diseased group. Moreover, tumor necrosis factor-alpha (TNF- α) and monocyte chemoattractant protein-1 (MCP-1) levels decreased by 63 and 68%, respectively. Similarly, our gene expression data showed improvement in mice receiving combined therapy compared to other groups receiving single treatment, where cartilage oligomeric matrix protein (Comp), tissue inhibitor metalloproteinase-1 (Timp1), matrix metalloproteinase1 (Mmp-1), and IL-1 receptor (Il-1r) gene expression levels decreased by 75, 70, and 78%, respectively. Collectively, treatment with a combined therapy of MSC and IL-4 might have an efficient therapeutic effect on arthritis. Thus, further studies are needed to assess the potential of different MSC populations in conjugation with IL-4 in the treatment of experimental arthritis. Full article

(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)

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19 pages, 5197 KiB

Open AccessArticle

Characterization of Dermal Stem Cells of Diabetic Patients

by Letizia Ferroni, Chiara Gardin, Luca Dalla Paola, Gianluca Campo, Paolo Cimaglia, Gloria Bellin, Paolo Pinton and Barbara Zavan

Cells 2019, 8(7), 729; https://doi.org/10.3390/cells8070729 - 16 Jul 2019

Cited by 24 | Viewed by 4119

Abstract

Diabetic foot ulcers (DFUs) are lesions that involve loss of epithelium and dermis, sometimes involving deep structures, compartments, and bones. The aim of this work is to investigate the innate regenerative properties of dermal tissue around ulcers by the identification and analysis of [...] Read more.

Diabetic foot ulcers (DFUs) are lesions that involve loss of epithelium and dermis, sometimes involving deep structures, compartments, and bones. The aim of this work is to investigate the innate regenerative properties of dermal tissue around ulcers by the identification and analysis of resident dermal stem cells (DSCs). Dermal samples were taken at the edge of DFUs, and genes related to the wound healing process were analyzed by the real-time PCR array. The DSCs were isolated and analyzed by immunofluorescence, flow cytometry, and real-time PCR array to define their stemness properties. The gene expression profile of dermal tissue showed a dysregulation in growth factors, metalloproteinases, collagens, and integrins involved in the wound healing process. In the basal condition, diabetic DSCs adhered on the culture plate with spindle-shaped fibroblast-like morphology. They were positive to the mesenchymal stem cells markers CD44, CD73, CD90, and CD105, but negative for the hematopoietic markers CD14, CD34, CD45, and HLA-DR. In diabetic DSCs, the transcription of genes related to self-renewal and cell division were equivalent to that in normal DSCs. However, the expression of CCNA2, CCND2, CDK1, ALDH1A1, and ABCG2 was downregulated compared with that of normal DSCs. These genes are also related to cell cycle progression and stem cell maintenance. Further investigation will improve the understanding of the molecular mechanisms by which these genes together govern cell proliferation, revealing new strategies useful for future treatment of DFUs. Full article

(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)

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20 pages, 3647 KiB

Open AccessArticle

Administration of Tonsil-Derived Mesenchymal Stem Cells Improves Glucose Tolerance in High Fat Diet-Induced Diabetic Mice via Insulin-Like Growth Factor-Binding Protein 5-Mediated Endoplasmic Reticulum Stress Modulation

by Younghay Lee, Sun-Hye Shin, Kyung-Ah Cho, Yu-Hee Kim, So-Youn Woo, Han Su Kim, Sung-Chul Jung, Inho Jo, Hee-Sook Jun, Woo-Jae Park, Joo-Won Park and Kyung-Ha Ryu

Cells 2019, 8(4), 368; https://doi.org/10.3390/cells8040368 - 23 Apr 2019

Cited by 14 | Viewed by 4795

Abstract

Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder accompanied by high blood glucose, insulin resistance, and relative insulin deficiency. Endoplasmic reticulum (ER) stress induced by high glucose and free fatty acids has been suggested as one of the main causes [...] Read more.

Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder accompanied by high blood glucose, insulin resistance, and relative insulin deficiency. Endoplasmic reticulum (ER) stress induced by high glucose and free fatty acids has been suggested as one of the main causes of β-cell dysfunction and death in T2DM. Stem cell-derived insulin-secreting cells were recently suggested as a novel therapy for diabetes. In the present study, we demonstrate the therapeutic potential of tonsil-derived mesenchymal stem cells (TMSCs) to treat high-fat diet (HFD)-induced T2DM. To explore whether TMSC administration can alleviate T2DM, TMSCs were intraperitoneally injected in HFD-induced T2DM mice once every 2 weeks. TMSC injection markedly improved glucose tolerance and glucose-stimulated insulin secretion and prevented HFD-induced pancreatic β-cell hypertrophy and cell death. In addition, TMSC injection relieved the ER-stress response and preserved gene expression related to glucose sensing and insulin secretion. Moreover, administration of TMSC-derived conditioned medium induced similar therapeutic outcomes, suggesting paracrine effects. Finally, proteomic analysis revealed high secretion of insulin-like growth factor-binding protein 5 by TMSCs, and its expression was critical for the protective effects of TMSCs against HFD-induced glucose intolerance and ER-stress response in pancreatic islets. TMSC administration can alleviate HFD-induced-T2DM via preserving pancreatic islets and their function. These results provide novel evidence of TMSCs as an ER-stress modulator that may be a novel, alternative cell therapy for T2DM. Full article

(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)

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17 pages, 1919 KiB

Open AccessArticle

Subcutaneous Maturation of Neural Stem Cell-Loaded Hydrogels Forms Region-Specific Neuroepithelium

by Mahmoud Farrag and Nic D. Leipzig

Cells 2018, 7(10), 173; https://doi.org/10.3390/cells7100173 - 17 Oct 2018

Cited by 13 | Viewed by 4572

Abstract

A combinatorial approach integrating stem cells and capable of exploiting available cues is likely needed to regenerate lost neural tissues and ultimately restore neurologic functions. This study investigates the effects of the subcutaneous maturation of adult-derived neural stem cell (aNSCs) seeded into biomaterial [...] Read more.

A combinatorial approach integrating stem cells and capable of exploiting available cues is likely needed to regenerate lost neural tissues and ultimately restore neurologic functions. This study investigates the effects of the subcutaneous maturation of adult-derived neural stem cell (aNSCs) seeded into biomaterial constructs on aNSC differentiation and ultimate regional neuronal identity as a first step toward a future spinal cord injury treatment. To achieve this, we encapsulated rat aNSCs in chitosan-based hydrogels functionalized with immobilized azide-tagged interferon-γ inside a chitosan conduit. Then, we implanted these constructs in the subcutaneous tissues in the backs of rats in the cervical, thoracic, and lumbar regions for 4, 6, and 8 weeks. After harvesting the scaffolds, we analyzed cell differentiation qualitatively using immunohistochemical analysis and quantitatively using RT-qPCR. Results revealed that the hydrogels supported aNSC survival and differentiation up to 4 weeks in the subcutaneous environment as marked by the expression of several neurogenesis markers. Most interesting, the aNSCs expressed region-specific Hox genes corresponding to their region of implantation. This study lays the groundwork for further translational work to recapitulate the potentially undiscovered patterning cues in the subcutaneous tissue and provide support for the conceptual premise that our bioengineering approach can form caudalized region-specific neuroepithelium. Full article

(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)

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Review

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13 pages, 693 KiB

Open AccessReview

Stem Cell-Derived Extracellular Vesicles and Kidney Regeneration

by Cristina Grange, Renata Skovronova, Federica Marabese and Benedetta Bussolati

Cells 2019, 8(10), 1240; https://doi.org/10.3390/cells8101240 - 11 Oct 2019

Cited by 88 | Viewed by 9911

Abstract

Extracellular vesicles (EVs) are membranous vesicles containing active proteins, lipids, and different types of genetic material such as miRNAs, mRNAs, and DNAs related to the characteristics of the originating cell. They possess a distinctive capacity to communicate over long distances. EVs have been [...] Read more.

Extracellular vesicles (EVs) are membranous vesicles containing active proteins, lipids, and different types of genetic material such as miRNAs, mRNAs, and DNAs related to the characteristics of the originating cell. They possess a distinctive capacity to communicate over long distances. EVs have been involved in the modulation of several pathophysiological conditions and, more importantly, stem cell-derived EVs appear as a new promising therapeutic option. In fact, several reports provide convincing evidence of the regenerative potential of EVs released by stem cells and, in particular, mesenchymal stromal cells (MSCs) in different kidney injury models. Described mechanisms involve the reprogramming of injured cells, cell proliferation and angiogenesis, and inhibition of cell apoptosis and inflammation. Besides, the therapeutic use of MSC-EVs in clinical trials is under investigation. This review will focus on MSC-EV applications in preclinical models of acute and chronic renal damage including recent data on their use in kidney transplant conditioning. Moreover, ongoing clinical trials are described. Finally, new strategies to broaden and enhance EV therapeutic efficacy by engineering are discussed. Full article

(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)

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18 pages, 843 KiB

Open AccessReview

Mesenchymal Stem Cell Migration and Tissue Repair

by Xiaorong Fu, Ge Liu, Alexander Halim, Yang Ju, Qing Luo and Guanbin Song

Cells 2019, 8(8), 784; https://doi.org/10.3390/cells8080784 - 28 Jul 2019

Cited by 673 | Viewed by 26662

Abstract

Mesenchymal stem cells (MSCs) are multilineage cells with the ability to self-renew and differentiate into a variety of cell types, which play key roles in tissue healing and regenerative medicine. Bone marrow-derived mesenchymal stem cells (BMSCs) are the most frequently used stem cells [...] Read more.

Mesenchymal stem cells (MSCs) are multilineage cells with the ability to self-renew and differentiate into a variety of cell types, which play key roles in tissue healing and regenerative medicine. Bone marrow-derived mesenchymal stem cells (BMSCs) are the most frequently used stem cells in cell therapy and tissue engineering. However, it is prerequisite for BMSCs to mobilize from bone marrow and migrate into injured tissues during the healing process, through peripheral circulation. The migration of BMSCs is regulated by mechanical and chemical factors in this trafficking process. In this paper, we review the effects of several main regulatory factors on BMSC migration and its underlying mechanism; discuss two critical roles of BMSCs—namely, directed differentiation and the paracrine function—in tissue repair; and provide insight into the relationship between BMSC migration and tissue repair, which may provide a better guide for clinical applications in tissue repair through the efficient regulation of BMSC migration. Full article

(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)

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21 pages, 389 KiB

Open AccessEditor’s ChoiceReview

Advances in Regenerative Stem Cell Therapy in Androgenic Alopecia and Hair Loss: Wnt Pathway, Growth-Factor, and Mesenchymal Stem Cell Signaling Impact Analysis on Cell Growth and Hair Follicle Development

by Pietro Gentile and Simone Garcovich

Cells 2019, 8(5), 466; https://doi.org/10.3390/cells8050466 - 16 May 2019

Cited by 209 | Viewed by 29003

Abstract

The use of stem cells has been reported to improve hair regrowth in several therapeutic strategies, including reversing the pathological mechanisms, that contribute to hair loss, regeneration of hair follicles, or creating hair using the tissue-engineering approach. Although various promising stem cell approaches [...] Read more.

The use of stem cells has been reported to improve hair regrowth in several therapeutic strategies, including reversing the pathological mechanisms, that contribute to hair loss, regeneration of hair follicles, or creating hair using the tissue-engineering approach. Although various promising stem cell approaches are progressing via pre-clinical models to clinical trials, intraoperative stem cell treatments with a one-step procedure offer a quicker result by incorporating an autologous cell source without manipulation, which may be injected by surgeons through a well-established clinical practice. Many authors have concentrated on adipose-derived stromal vascular cells due to their ability to separate into numerous cell genealogies, platelet-rich plasma for its ability to enhance cell multiplication and neo-angiogenesis, as well as human follicle mesenchymal stem cells. In this paper, the significant improvements in intraoperative stem cell approaches, from in vivo models to clinical investigations, are reviewed. The potential regenerative instruments and functions of various cell populaces in the hair regrowth process are discussed. The addition of Wnt signaling in dermal papilla cells is considered a key factor in stimulating hair growth. Mesenchymal stem cell-derived signaling and growth factors obtained by platelets influence hair growth through cellular proliferation to prolong the anagen phase (FGF-7), induce cell growth (ERK activation), stimulate hair follicle development (β-catenin), and suppress apoptotic cues (Bcl-2 release and Akt activation). Full article

(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)

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