International Journal of Molecular Sciences

Editorial

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4 pages, 188 KiB

Open AccessEditorial

Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration

by Aleksandra Klimczak

Int. J. Mol. Sci. 2022, 23(12), 6652; https://doi.org/10.3390/ijms23126652 - 15 Jun 2022

Cited by 4 | Viewed by 1528

Abstract

Mesenchymal stem/stromal cells (MSC) have been extensively studied over the last 30 years in the context of their regenerative and immunomodulatory activities for potential application in regenerative medicine [...] Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

Research

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18 pages, 5300 KiB

Open AccessArticle

Extracellular Vesicles Derived from Human Liver Stem Cells Attenuate Chronic Kidney Disease Development in an In Vivo Experimental Model of Renal Ischemia and Reperfusion Injury

by Stefania Bruno, Giulia Chiabotto, Massimo Cedrino, Elena Ceccotti, Chiara Pasquino, Samuela De Rosa, Cristina Grange, Stefania Tritta and Giovanni Camussi

Int. J. Mol. Sci. 2022, 23(3), 1485; https://doi.org/10.3390/ijms23031485 - 27 Jan 2022

Cited by 9 | Viewed by 3514

Abstract

The potential therapeutic effect of extracellular vesicles (EVs) that are derived from human liver stem cells (HLSCs) has been tested in an in vivo model of renal ischemia and reperfusion injury (IRI), that induce the development of chronic kidney disease (CKD). EVs were [...] Read more.

The potential therapeutic effect of extracellular vesicles (EVs) that are derived from human liver stem cells (HLSCs) has been tested in an in vivo model of renal ischemia and reperfusion injury (IRI), that induce the development of chronic kidney disease (CKD). EVs were administered intravenously immediately after the IRI and three days later, then their effect was tested at different time points to evaluate how EV-treatment might interfere with fibrosis development. In IRI-mice that were sacrificed two months after the injury, EV- treatment decreased the development of interstitial fibrosis at the histological and molecular levels. Furthermore, the expression levels of pro-inflammatory genes and of epithelial–mesenchymal transition (EMT) genes were significantly reverted by EV-treatment. In IRI-mice that were sacrificed at early time points (two and three days after the injury), functional and histological analyses showed that EV-treatment induced an amelioration of the acute kidney injury (AKI) that was induced by IRI. Interestingly, at the molecular level, a reduction of pro-fibrotic and EMT-genes in sacrificed IRI-mice was observed at days two and three after the injury. These data indicate that in renal IRI, treatment with HLSC-derived EVs improves AKI and interferes with the development of subsequent CKD by modulating the genes that are involved in fibrosis and EMT. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

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12 pages, 1220 KiB

Open AccessArticle

Secretome Analysis of Rabbit and Human Mesenchymal Stem and Endothelial Progenitor Cells: A Comparative Study

by Jaromír Vašíček, Andrej Baláži, Mária Tirpáková, Andrea Svoradová, Ľubomír Ondruška, Vladimír Parkányi and Peter Chrenek

Int. J. Mol. Sci. 2021, 22(22), 12283; https://doi.org/10.3390/ijms222212283 - 13 Nov 2021

Cited by 6 | Viewed by 2320

Abstract

Human adipose tissue-derived mesenchymal stem cells (AT-MSCs) have been studied several years for their immunomodulatory effect through the paracrine mechanism and cytokine secretion. In combination with endothelial progenitor cells (EPCs), MSCs have great therapeutical potential for the repair of endothelium and wound healing. [...] Read more.

Human adipose tissue-derived mesenchymal stem cells (AT-MSCs) have been studied several years for their immunomodulatory effect through the paracrine mechanism and cytokine secretion. In combination with endothelial progenitor cells (EPCs), MSCs have great therapeutical potential for the repair of endothelium and wound healing. However, little is known about the cytokine profile of rabbit AT-MSCs or even EPCs. The aim of this study was to analyze the secretomes of these rabbit stem/progenitor cells. A large-scale human cytokine array (up to 80 cytokines) was used to identify and compare cytokines secreted into conditioned media of human and rabbit AT-MSCs as well as HUVECs and rabbit EPCs. Few cytokines were highly expressed by human AT-MSCs (TIMP-2, TIMP-1), HUVECs (MCP-1, TIMP-2, GRO, Angiogenin, IL-8, TIMP-1), or by rabbit EPCs (TIMP-2). Several cytokines have moderate expression by human (MCP-1, GRO, Angiogenin, TGF-β 2, IL-8, LIF, IL-6, Osteopontin, Osteoprotegerin) and rabbit AT-MSCs (TIMP-2, TGF-β 2, LIF, Osteopontin, IL-8, IL-5, IL-3) or by HUVECs (IL-6, MIF, TGF-β 2, GCP-2, IGFBP-2, Osteoprotegerin, EGF, LIF, PDGF-BB, MCP-3, Osteopontin, Leptin, IL-5, ENA-78, TNF-β) and rabbit EPCs (TGF-β 2, Osteopontin, GRO, LIF, IL-8, IL-5, IL-3). In conclusion, the proposed method seems to be useful for the secretome analysis of rabbit stem/progenitor cells. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

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18 pages, 5421 KiB

Open AccessArticle

HATMSC Secreted Factors in the Hydrogel as a Potential Treatment for Chronic Wounds—In Vitro Study

by Honorata Kraskiewicz, Piotr Hinc, Agnieszka Krawczenko, Aleksandra Bielawska-Pohl, Maria Paprocka, Danuta Witkowska, Isma Liza Mohd Isa, Abhay Pandit and Aleksandra Klimczak

Int. J. Mol. Sci. 2021, 22(22), 12241; https://doi.org/10.3390/ijms222212241 - 12 Nov 2021

Cited by 10 | Viewed by 2962

Abstract

Mesenchymal stem cells (MSCs) can improve chronic wound healing; however, recent studies suggest that the therapeutic effect of MSCs is mediated mainly through the growth factors and cytokines secreted by these cells, referred to as the MSC secretome. To overcome difficulties related to [...] Read more.

Mesenchymal stem cells (MSCs) can improve chronic wound healing; however, recent studies suggest that the therapeutic effect of MSCs is mediated mainly through the growth factors and cytokines secreted by these cells, referred to as the MSC secretome. To overcome difficulties related to the translation of cell therapy into clinical use such as efficacy, safety and cost, we propose a hydrogel loaded with a secretome from the recently established human adipose tissue mesenchymal stem cell line (HATMSC2) as a potential treatment for chronic wounds. Biocompatibility and biological activity of hydrogel-released HATMSC2 supernatant were investigated in vitro by assessing the proliferation and metabolic activity of human fibroblast, endothelial cells and keratinocytes. Hydrogel degradation was measured using hydroxyproline assay while protein released from the hydrogel was assessed by interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) ELISAs. Pro-angiogenic activity of the developed treatment was assessed by tube formation assay while the presence of pro-angiogenic miRNAs in the HATMSC2 supernatant was investigated using real-time RT-PCR. The results demonstrated that the therapeutic effect of the HATMSC2-produced factors is maintained following incorporation into collagen hydrogel as confirmed by increased proliferation of skin-origin cells and improved angiogenic properties of endothelial cells. In addition, HATMSC2 supernatant revealed antimicrobial activity, and which therefore, in combination with the hydrogel has a potential to be used as advanced wound-healing dressing. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

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21 pages, 3994 KiB

Open AccessArticle

Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells

by Tzu-Yin Chen, Chia-Hao Liu, Tsung-Hsien Chen, Mei-Ru Chen, Shan-Wen Liu, Pinpin Lin and Kurt Ming-Chao Lin

Int. J. Mol. Sci. 2021, 22(21), 12069; https://doi.org/10.3390/ijms222112069 - 8 Nov 2021

Cited by 5 | Viewed by 3055

Abstract

The role of the epithelial–mesenchymal transition (EMT) in lung epithelial cells is increasingly being recognized as a key stage in the development of COPD, fibrosis, and lung cancers, which are all highly associated with cigarette smoking and with exposure to second-hand smoke. Using [...] Read more.

The role of the epithelial–mesenchymal transition (EMT) in lung epithelial cells is increasingly being recognized as a key stage in the development of COPD, fibrosis, and lung cancers, which are all highly associated with cigarette smoking and with exposure to second-hand smoke. Using the exposure of human lung cancer epithelial A549 cells and non-cancerous Beas-2B cells to sidestream cigarette smoke extract (CSE) as a model, we studied the protective effects of adipose-derived stem cell-conditioned medium (ADSC-CM) against CSE-induced cell death and EMT. CSE dose-dependently induced cell death, decreased epithelial markers, and increased the expression of mesenchymal markers. Upstream regulator analysis of differentially expressed genes after CSE exposure revealed similar pathways as those observed in typical EMT induced by TGF-β1. CSE-induced cell death was clearly attenuated by ADSC-CM but not by other control media, such as a pass-through fraction of ADSC-CM or A549-CM. ADSC-CM effectively inhibited CSE-induced EMT and was able to reverse the gradual loss of epithelial marker expression associated with TGF-β1 treatment. CSE or TGF-β1 enhanced the speed of A549 migration by 2- to 3-fold, and ADSC-CM was effective in blocking the cell migration induced by either agent. Future work will build on the results of this in vitro study by defining the molecular mechanisms through which ADSC-CM protects lung epithelial cells from EMT induced by toxicants in second-hand smoke. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

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15 pages, 2002 KiB

Open AccessArticle

Mesenchymal Stem Cell-Conditioned Media Regulate Steroidogenesis and Inhibit Androgen Secretion in a PCOS Cell Model via BMP-2

by Rishi Man Chugh, Hang-soo Park, Sahar Esfandyari, Amro Elsharoud, Mara Ulin and Ayman Al-Hendy

Int. J. Mol. Sci. 2021, 22(17), 9184; https://doi.org/10.3390/ijms22179184 - 25 Aug 2021

Cited by 27 | Viewed by 4246

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. Previous studies have demonstrated the therapeutic efficacy of human bone marrow mesenchymal stem cells (BM-hMSCs) for PCOS; however, the regulatory mechanism remains unknown. Bone morphogenetic proteins (BMPs) secreted by BM-hMSCs may [...] Read more.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. Previous studies have demonstrated the therapeutic efficacy of human bone marrow mesenchymal stem cells (BM-hMSCs) for PCOS; however, the regulatory mechanism remains unknown. Bone morphogenetic proteins (BMPs) secreted by BM-hMSCs may underlie the therapeutic effect of these cells on PCOS, based on the ability of BMPs to modulate androgen production and alter steroidogenesis pathway enzymes. In this study, we analyze the effect of BMP-2 on androgen production and steroidogenic pathway enzymes in H295R cells as a human PCOS in vitro cell model. In H295R cells, BMP-2 significantly suppressed cell proliferation, androgen production, and expression of androgen-synthesizing genes, as well as inflammatory gene expression. Furthermore, H295R cells treated with the BM-hMSCs secretome in the presence of neutralizing BMP-2 antibody or with BMP-2 gene knockdown showed augmented expression of androgen-producing genes. Taken together, these results indicate that BMP-2 is a key player mediating the favorable effects of the BM-hMSCs secretome in a human PCOS cell model. BMP-2 overexpression could increase the efficacy of BM-hMSC-based therapy, serving as a novel stem cell therapy for patients with intractable PCOS. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

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15 pages, 5037 KiB

Open AccessArticle

Effect of Different Bone Grafting Materials and Mesenchymal Stem Cells on Bone Regeneration: A Micro-Computed Tomography and Histomorphometric Study in a Rabbit Calvarial Defect Model

by Shiau-Ting Shiu, Wei-Fang Lee, Sheng-Min Chen, Liu-Ting Hao, Yuan-Ting Hung, Pin-Chuang Lai and Sheng-Wei Feng

Int. J. Mol. Sci. 2021, 22(15), 8101; https://doi.org/10.3390/ijms22158101 - 28 Jul 2021

Cited by 22 | Viewed by 5066

Abstract

This study evaluated the new bone formation potential of micro–macro biphasic calcium phosphate (MBCP) and Bio-Oss grafting materials with and without dental pulp-derived mesenchymal stem cells (DPSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) in a rabbit calvarial bone defect model. The surface [...] Read more.

This study evaluated the new bone formation potential of micro–macro biphasic calcium phosphate (MBCP) and Bio-Oss grafting materials with and without dental pulp-derived mesenchymal stem cells (DPSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) in a rabbit calvarial bone defect model. The surface structure of the grafting materials was evaluated using a scanning electron microscope (SEM). The multipotent differentiation characteristics of the DPSCs and BMSCs were assessed. Four circular bone defects were created in the calvarium of 24 rabbits and randomly allocated to eight experimental groups: empty control, MBCP, MBCP+DPSCs, MBCP+BMSCs, Bio-Oss+DPSCs, Bio-Oss+BMSCs, and autogenous bone. A three-dimensional analysis of the new bone formation was performed using micro-computed tomography (micro-CT) and a histological study after 2, 4, and 8 weeks of healing. Homogenously porous structures were observed in both grafting materials. The BMSCs revealed higher osteogenic differentiation capacities, whereas the DPSCs exhibited higher colony-forming units. The micro-CT and histological analysis findings for the new bone formation were consistent. In general, the empty control showed the lowest bone regeneration capacity throughout the experimental period. By contrast, the percentage of new bone formation was the highest in the autogenous bone group after 2 (39.4% ± 4.7%) and 4 weeks (49.7% ± 1.5%) of healing (p < 0.05). MBCP and Bio-Oss could provide osteoconductive support and prevent the collapse of the defect space for new bone formation. In addition, more osteoblastic cells lining the surface of the newly formed bone and bone grafting materials were observed after incorporating the DPSCs and BMSCs. After 8 weeks of healing, the autogenous bone group (54.9% ± 6.1%) showed a higher percentage of new bone formation than the empty control (35.3% ± 0.5%), MBCP (38.3% ± 6.0%), MBCP+DPSC (39.8% ± 5.7%), Bio-Oss (41.3% ± 3.5%), and Bio-Oss+DPSC (42.1% ± 2.7%) groups. Nevertheless, the percentage of new bone formation did not significantly differ between the MBCP+BMSC (47.2% ± 8.3%) and Bio-Oss+BMSC (51.2% ± 9.9%) groups and the autogenous bone group. Our study results demonstrated that autogenous bone is the gold standard. Both the DPSCs and BMSCs enhanced the osteoconductive capacities of MBCP and Bio-Oss. In addition, the efficiency of the BMSCs combined with MBCP and Bio-Oss was comparable to that of the autogenous bone after 8 weeks of healing. These findings provide effective strategies for the improvement of biomaterials and MSC-based bone tissue regeneration. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

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17 pages, 7095 KiB

Open AccessArticle

Comparative Transcriptome Analysis of Human Adipose-Derived Stem Cells Undergoing Osteogenesis in 2D and 3D Culture Conditions

by Byung-Chul Kim, Kyu Hwan Kwack, Jeewan Chun and Jae-Hyung Lee

Int. J. Mol. Sci. 2021, 22(15), 7939; https://doi.org/10.3390/ijms22157939 - 26 Jul 2021

Cited by 9 | Viewed by 3707

Abstract

Human adipose-derived stem cells (hADSCs) are types of mesenchymal stem cells (MSCs) that have been used as tissue engineering models for bone, cartilage, muscle, marrow stroma, tendon, fat and other connective tissues. Tissue regeneration materials composed of hADSCs have the potential to play [...] Read more.

Human adipose-derived stem cells (hADSCs) are types of mesenchymal stem cells (MSCs) that have been used as tissue engineering models for bone, cartilage, muscle, marrow stroma, tendon, fat and other connective tissues. Tissue regeneration materials composed of hADSCs have the potential to play an important role in reconstituting damaged tissue or diseased mesenchymal tissue. In this study, we assessed and investigated the osteogenesis of hADSCs in both two-dimensional (2D) and three-dimensional (3D) culture conditions. We confirmed that the hADSCs successfully differentiated into bone tissues by ARS staining and quantitative RT–PCR. To gain insight into the detailed biological difference between the two culture conditions, we profiled the overall gene expression by analyzing the whole transcriptome sequencing data using various bioinformatic methods. We profiled the overall gene expression through RNA-Seq and further analyzed this using various bioinformatic methods. During differential gene expression testing, significant differences in the gene expressions between hADSCs cultured in 2D and 3D conditions were observed. The genes related to skeletal development, bone development and bone remodeling processes were overexpressed in the 3D culture condition as compared to the 2D culture condition. In summary, our RNA-Seq-based study proves effective in providing new insights that contribute toward achieving a genome-wide understanding of gene regulation in mesenchymal stem cell osteogenic differentiation and bone tissue regeneration within the 3D culture system. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

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16 pages, 4807 KiB

Open AccessArticle

Menstrual Blood-Derived Endometrial Stem Cells’ Impact for the Treatment Perspective of Female Infertility

by Giedrė Skliutė, Raminta Baušytė, Veronika Borutinskaitė, Giedrė Valiulienė, Algirdas Kaupinis, Mindaugas Valius, Diana Ramašauskaitė and Rūta Navakauskienė

Int. J. Mol. Sci. 2021, 22(13), 6774; https://doi.org/10.3390/ijms22136774 - 24 Jun 2021

Cited by 20 | Viewed by 4634

Abstract

When looking for the causes and treatments of infertility, much attention is paid to one of the reproductive tissues—the endometrium. Therefore, endometrial stem cells are an attractive target for infertility studies in women of unexplained origin. Menstrual blood stem cells (MenSCs) are morphologically [...] Read more.

When looking for the causes and treatments of infertility, much attention is paid to one of the reproductive tissues—the endometrium. Therefore, endometrial stem cells are an attractive target for infertility studies in women of unexplained origin. Menstrual blood stem cells (MenSCs) are morphologically and functionally similar to cells derived directly from the endometrium; with dual expression of mesenchymal and embryonic cell markers, they proliferate and regenerate better than bone marrow mesenchymal stem cells. In addition, menstrual blood stem cells are extracted in a non-invasive and painless manner. In our study, we analyzed the characteristics and the potential for decidualization of menstrual blood stem cells isolated from healthy volunteers and women diagnosed with infertility. We demonstrated that MenSCs express CD44, CD166, CD16, CD15, BMSC, CD56, CD13 and HLA-ABC surface markers, have proliferative properties, and after induction of menstrual stem cell differentiation into epithelial direction, expression of genes related to decidualization (PRL, ESR, IGFBP and FOXO1) and angiogenesis (HIF1, VEGFR2 and VEGFR3) increased. Additionally, the p53, p21, H3K27me3 and HyperAcH4 proteins’ expression increased during MenSCs decidualization, they secrete proteins that are involved in the regulation of the actin cytoskeleton, estrogen and relaxin signaling pathways and the management of inflammatory processes. Our findings reveal the potential use of MenSCs for the treatment of reproductive disorders. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

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18 pages, 8805 KiB

Open AccessArticle

Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration

by Elia Bari, Ilaria Roato, Giuseppe Perale, Filippo Rossi, Tullio Genova, Federico Mussano, Riccardo Ferracini, Marzio Sorlini, Maria Luisa Torre and Sara Perteghella

Int. J. Mol. Sci. 2021, 22(8), 4064; https://doi.org/10.3390/ijms22084064 - 14 Apr 2021

Cited by 15 | Viewed by 2864

Abstract

SmartBone^® (SB) is a biohybrid bone substitute advantageously proposed as a class III medical device for bone regeneration in reconstructive surgeries (oral, maxillofacial, orthopedic, and oncology). In the present study, a new strategy to improve SB osteoinductivity was developed. SB scaffolds were [...] Read more.

SmartBone^® (SB) is a biohybrid bone substitute advantageously proposed as a class III medical device for bone regeneration in reconstructive surgeries (oral, maxillofacial, orthopedic, and oncology). In the present study, a new strategy to improve SB osteoinductivity was developed. SB scaffolds were loaded with lyosecretome, a freeze-dried formulation of mesenchymal stem cell (MSC)-secretome, containing proteins and extracellular vesicles (EVs). Lyosecretome-loaded SB scaffolds (SBlyo) were prepared using an absorption method. A burst release of proteins and EVs (38% and 50% after 30 min, respectively) was observed, and then proteins were released more slowly with respect to EVs, most likely because they more strongly adsorbed onto the SB surface. In vitro tests were conducted using adipose tissue-derived stromal vascular fraction (SVF) plated on SB or SBlyo. After 14 days, significant cell proliferation improvement was observed on SBlyo with respect to SB, where cells filled the cavities between the native trabeculae. On SB, on the other hand, the process was still present, but tissue formation was less organized at 60 days. On both scaffolds, cells differentiated into osteoblasts and were able to mineralize after 60 days. Nonetheless, SBlyo showed a higher expression of osteoblast markers and a higher quantity of newly formed trabeculae than SB alone. The quantification analysis of the newly formed mineralized tissue and the immunohistochemical studies demonstrated that SBlyo induces bone formation more effectively. This osteoinductive effect is likely due to the osteogenic factors present in the lyosecretome, such as fibronectin, alpha-2-macroglobulin, apolipoprotein A, and TGF-β. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

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Review

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11 pages, 7587 KiB

Open AccessReview

Osteocytes: Their Lacunocanalicular Structure and Mechanoresponses

by Takeshi Moriishi and Toshihisa Komori

Int. J. Mol. Sci. 2022, 23(8), 4373; https://doi.org/10.3390/ijms23084373 - 15 Apr 2022

Cited by 10 | Viewed by 3287

Abstract

Osteocytes connect with neighboring osteocytes and osteoblasts through their processes and form an osteocyte network. Shear stress on osteocytes, which is induced by fluid flow in the lacunae and canaliculi, has been proposed as an important mechanism for mechanoresponses. The lacunocanalicular structure is [...] Read more.

Osteocytes connect with neighboring osteocytes and osteoblasts through their processes and form an osteocyte network. Shear stress on osteocytes, which is induced by fluid flow in the lacunae and canaliculi, has been proposed as an important mechanism for mechanoresponses. The lacunocanalicular structure is differentially developed in the compression and tension sides of femoral cortical bone and the compression side is more organized and has denser and thinner canaliculi. Mice with an impaired lacunocanalicular structure may be useful for evaluation of the relationship between lacunocanalicular structure and mechanoresponses, although their bone component cells are not normal. We show three examples of mice with an impaired lacunocanalicular structure. Ablation of osteocytes by diphtheria toxin caused massive osteocyte apoptosis, necrosis or secondary necrosis that occurred after apoptosis. Osteoblast-specific Bcl2 transgenic mice were found to have a reduced number of osteocyte processes and canaliculi, which caused massive osteocyte apoptosis and a completely interrupted lacunocanalicular network. Osteoblast-specific Sp7 transgenic mice were also revealed to have a reduced number of osteocyte processes and canaliculi, as well as an impaired, but functionally connected, lacunocanalicular network. Here, we show the phenotypes of these mice in physiological and unloaded conditions and deduce the relationship between lacunocanalicular structure and mechanoresponses. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

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20 pages, 1984 KiB

Open AccessReview

Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells and Their Contribution to Angiogenic Processes in Tissue Regeneration

by Agnieszka Krawczenko and Aleksandra Klimczak

Int. J. Mol. Sci. 2022, 23(5), 2425; https://doi.org/10.3390/ijms23052425 - 22 Feb 2022

Cited by 40 | Viewed by 4620

Abstract

Mesenchymal stem/stromal cells (MSCs) are widely described in the context of their regenerative and immunomodulatory activity. MSCs are isolated from various tissues and organs. The most frequently described sources are bone marrow and adipose tissue. As stem cells, MSCs are able to differentiate [...] Read more.

Mesenchymal stem/stromal cells (MSCs) are widely described in the context of their regenerative and immunomodulatory activity. MSCs are isolated from various tissues and organs. The most frequently described sources are bone marrow and adipose tissue. As stem cells, MSCs are able to differentiate into other cell lineages, but they are usually reported with respect to their paracrine potential. In this review, we focus on MSCs derived from adipose tissue (AT-MSCs) and their secretome in regeneration processes. Special attention is given to the contribution of AT-MSCs and their derivatives to angiogenic processes described mainly in the context of angiogenic dysfunction. Finally, we present clinical trials registered to date that concern the application of AT-MSCs and their secretome in various medical conditions. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

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16 pages, 1428 KiB

Open AccessReview

Regenerative Potential of Mesenchymal Stem Cells’ (MSCs) Secretome for Liver Fibrosis Therapies

by Simona-Rebeca Nazarie (Ignat), Sami Gharbia, Anca Hermenean, Sorina Dinescu and Marieta Costache

Int. J. Mol. Sci. 2021, 22(24), 13292; https://doi.org/10.3390/ijms222413292 - 10 Dec 2021

Cited by 25 | Viewed by 4760

Abstract

Chronic liver injuries lead to liver fibrosis and then to end-stage liver cirrhosis. Liver transplantation is often needed as a course of treatment for patients in critical conditions, but limitations associated with transplantation prompted the continuous search for alternative therapeutic strategies. Cell therapy [...] Read more.

Chronic liver injuries lead to liver fibrosis and then to end-stage liver cirrhosis. Liver transplantation is often needed as a course of treatment for patients in critical conditions, but limitations associated with transplantation prompted the continuous search for alternative therapeutic strategies. Cell therapy with stem cells has emerged as an attractive option in order to stimulate tissue regeneration and liver repair. Transplanted mesenchymal stem cells (MSCs) could trans-differentiate into hepatocyte-like cells and, moreover, show anti-fibrotic and immunomodulatory effects. However, cell transplantation may lead to some uncontrolled side effects, risks associated with tumorigenesis, and cell rejection. MSCs’ secretome includes a large number of soluble factors and extracellular vesicles (EVs), through which they exert their therapeutic role. This could represent a cell-free strategy, which is safer and more effective than MSC transplantation. In this review, we focus on cell therapies based on MSCs and how the MSCs’ secretome impacts the mechanisms associated with liver diseases. Moreover, we discuss the important therapeutic role of EVs and how their properties could be further used in liver regeneration. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

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39 pages, 2363 KiB

Open AccessReview

Dental Pulp Stem Cell-Derived Secretome and Its Regenerative Potential

by Julia K. Bar, Anna Lis-Nawara and Piotr Grzegorz Grelewski

Int. J. Mol. Sci. 2021, 22(21), 12018; https://doi.org/10.3390/ijms222112018 - 6 Nov 2021

Cited by 47 | Viewed by 7382

Abstract

The therapeutic potential of the dental pulp stem (DSC) cell-derived secretome, consisting of various biomolecules, is undergoing intense research. Despite promising in vitro and in vivo studies, most DSC secretome-based therapies have not been implemented in human medicine because the paracrine effect of [...] Read more.

The therapeutic potential of the dental pulp stem (DSC) cell-derived secretome, consisting of various biomolecules, is undergoing intense research. Despite promising in vitro and in vivo studies, most DSC secretome-based therapies have not been implemented in human medicine because the paracrine effect of the bioactive factors secreted by human dental pulp stem cells (hDPSCs) and human exfoliated deciduous teeth (SHEDs) is not completely understood. In this review, we outline the current data on the hDPSC- and SHED-derived secretome as a potential candidate in the regeneration of bone, cartilage, and nerve tissue. Published reports demonstrate that the dental MSC-derived secretome/conditional medium may be effective in treating neurodegenerative diseases, neural injuries, cartilage defects, and repairing bone by regulating neuroprotective, anti-inflammatory, antiapoptotic, and angiogenic processes through secretome paracrine mechanisms. Dental MSC-secretomes, similarly to the bone marrow MSC-secretome activate molecular and cellular mechanisms, which determine the effectiveness of cell-free therapy. Many reports emphasize that dental MSC-derived secretomes have potential application in tissue-regenerating therapy due to their multidirectional paracrine effect observed in the therapy of many different injured tissues. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

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13 pages, 327 KiB

Open AccessReview

The Role of MSCs and Cell Fusion in Tissue Regeneration

by Jessica Dörnen and Thomas Dittmar

Int. J. Mol. Sci. 2021, 22(20), 10980; https://doi.org/10.3390/ijms222010980 - 12 Oct 2021

Cited by 11 | Viewed by 2893

Abstract

Regenerative medicine is concerned with the investigation of therapeutic agents that can be used to promote the process of regeneration after injury or in different diseases. Mesenchymal stem/stromal cells (MSCs) and their secretome—including extracellular vesicles (EVs) are of great interest, due to their [...] Read more.

Regenerative medicine is concerned with the investigation of therapeutic agents that can be used to promote the process of regeneration after injury or in different diseases. Mesenchymal stem/stromal cells (MSCs) and their secretome—including extracellular vesicles (EVs) are of great interest, due to their role in tissue regeneration, immunomodulatory capacity and low immunogenicity. So far, clinical studies are not very conclusive as they show conflicting efficacies regarding the use of MSCs. An additional process possibly involved in regeneration might be cell fusion. This process occurs in both a physiological and a pathophysiological context and can be affected by immune response due to inflammation. In this review the role of MSCs and cell fusion in tissue regeneration is discussed. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

22 pages, 1370 KiB

Open AccessReview

Mesenchymal Stem/Stromal Cell Therapy in Blood–Brain Barrier Preservation Following Ischemia: Molecular Mechanisms and Prospects

by Phuong Thao Do, Chung-Che Wu, Yung-Hsiao Chiang, Chaur-Jong Hu and Kai-Yun Chen

Int. J. Mol. Sci. 2021, 22(18), 10045; https://doi.org/10.3390/ijms221810045 - 17 Sep 2021

Cited by 40 | Viewed by 4903

Abstract

Ischemic stroke is the leading cause of mortality and long-term disability worldwide. Disruption of the blood–brain barrier (BBB) is a prominent pathophysiological mechanism, responsible for a series of subsequent inflammatory cascades that exacerbate the damage to brain tissue. However, the benefit of recanalization [...] Read more.

Ischemic stroke is the leading cause of mortality and long-term disability worldwide. Disruption of the blood–brain barrier (BBB) is a prominent pathophysiological mechanism, responsible for a series of subsequent inflammatory cascades that exacerbate the damage to brain tissue. However, the benefit of recanalization is limited in most patients because of the narrow therapeutic time window. Recently, mesenchymal stem cells (MSCs) have been assessed as excellent candidates for cell-based therapy in cerebral ischemia, including neuroinflammatory alleviation, angiogenesis and neurogenesis promotion through their paracrine actions. In addition, accumulating evidence on how MSC therapy preserves BBB integrity after stroke may open up novel therapeutic targets for treating cerebrovascular diseases. In this review, we focus on the molecular mechanisms of MSC-based therapy in the ischemia-induced prevention of BBB compromise. Currently, therapeutic effects of MSCs for stroke are primarily based on the fundamental pathogenesis of BBB breakdown, such as attenuating leukocyte infiltration, matrix metalloproteinase (MMP) regulation, antioxidant, anti-inflammation, stabilizing morphology and crosstalk between cellular components of the BBB. We also discuss prospective studies to improve the effectiveness of MSC therapy through enhanced migration into defined brain regions of stem cells. Targeted therapy is a promising new direction and is being prioritized for extensive research. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration)

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