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Kranc W, Kaczmarek M, Kowalska K, Pieńkowski W, Ciesiółka S, Konwerska A, Mozdziak P, Brązert M, Jeseta M, Spaczyński RZ, Pawelczyk L, Kempisty B. Morphological characteristics, extracellular vesicle structure and stem-like specificity of human follicular fluid cell subpopulation during osteodifferentiation. Exp Mol Pathol 2025; 142:104965. [PMID: 40253818 DOI: 10.1016/j.yexmp.2025.104965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 03/28/2025] [Accepted: 04/03/2025] [Indexed: 04/22/2025]
Abstract
Extracellular vesicles can play an important role in the processes occurring after stem cell transplantation, preventing cell apoptosis, stimulating immunological processes, and promoting the synthesis of extracellular matrix. Human follicular fluid (FF) can be a source of a subpopulation of cells with mesenchymal stem cells (MSCs) properties. Moreover these subpopulations of FF cells can differentiate into osteoblasts. In presented studies flow cytometry of ovarian FF cells confirmed positive expression of MSCs markers such as: CD44, CD90, CD105, CD73 and negative expression of a hematopoietic marker: CD45. The CD90+, CD105+, CD45- cell subpopulation has been obtained during magnetic separation using appropriate antibodies conjugated with microbeads. The extracellular vesicles (EVs) secreted by the cells during osteodifferentiation process differed from those secreted by cells culture in the basal medium. Based on the previous and current electron microscopy research, changes in size, number, and shape would support the notion that released EVs could be crucial to the ovarian FF cell subpopulation differentiation process. Osteogenic differentiation has been confirmed via Alizarin red staining. Therefore, follicular fluid (FF) can be a new source of a cell subpopulation with MSC properties, with the cells capable of differentiating into the osteogenic lineage. EVs could play a key role as mediators in tissue regeneration, especially bone tissue regeneration.
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Affiliation(s)
- Wiesława Kranc
- Department of Anatomy, Poznan University of Medical Sciences, 6 Święcickiego St., 60-781 Poznan, Poland.
| | - Mariusz Kaczmarek
- Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Center, 15 Garbary St., 61-866 Poznań, Poland; Department of Cancer Immunology, Poznan University of Medical Sciences, 5 Garbary St., 61-866 Poznań, Poland.
| | - Katarzyna Kowalska
- Department of Histology and Embryology, Poznan University of Medical Sciences, 6 Swiecickiego St., 60-781 Poznan, Poland.
| | - Wojciech Pieńkowski
- Division of Perinatology and Women's Diseases, Poznan University of Medical Sciences, 33 Polna St. 60-535 Poznan, Poland.
| | - Sylwia Ciesiółka
- Department of Histology and Embryology, Poznan University of Medical Sciences, 6 Swiecickiego St., 60-781 Poznan, Poland.
| | - Aneta Konwerska
- Department of Histology and Embryology, Poznan University of Medical Sciences, 6 Swiecickiego St., 60-781 Poznan, Poland.
| | - Paul Mozdziak
- Prestage Department of Poultry Sciences, North Carolina State University, Raleigh, NC 27695, USA; Physiology Graduate Faculty, North Carolina State University, Raleigh, NC 27695, USA.
| | - Maciej Brązert
- Department of Diagnostic and Treatment of Infertility, Department of Gynecological Endocrinology and Infertility Treatment Karol Marcinkowski University, Poznan University of Medical Sciences, 33 Polna St., 60-535 Poznan, Poland.
| | - Michal Jeseta
- Department of Obstetrics and Gynecology, University Hospital and Masaryk University, 62500 Brno, Czechia.
| | - Robert Z Spaczyński
- Center for Gynecology, Obstetrics and Infertility Treatment Pastelova, Pastelowa 8, 60-198, Poznan, Poland..
| | - Leszek Pawelczyk
- Department of Diagnostic and Treatment of Infertility, Department of Gynecological Endocrinology and Infertility Treatment Karol Marcinkowski University, Poznan University of Medical Sciences, 33 Polna St., 60-535 Poznan, Poland.
| | - Bartosz Kempisty
- Physiology Graduate Faculty, North Carolina State University, Raleigh, NC 27695, USA; Department of Obstetrics and Gynecology, University Hospital and Masaryk University, 62500 Brno, Czechia; Division of Anatomy, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Chalubinskiego 6a, 50-368 Wroclaw, Poland; Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 1 Lwowska St., 87-100 Torun, Poland.
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Wang Y, Sun C, Liu Z, Zhang S, Gao K, Yi F, Zhou W, Liu H. Nanoengineered Endocytic Biomaterials for Stem Cell Therapy. ADVANCED FUNCTIONAL MATERIALS 2024; 34. [DOI: 10.1002/adfm.202410714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Indexed: 01/05/2025]
Abstract
AbstractStem cells, ideal for the tissue repair and regeneration, possess extraordinary capabilities of multidirectional differentiation and self‐renewal. However, the limited spontaneous differentiation potential makes it challenging to harness them for tissue repair without external intervention. Although conventional approaches using biomolecules, small organic molecules, and ions have shown specific and effective functions, they face challenges such as in vivo diffusion and degradation, poor internalization, and side effects on adjacent cells. Nanoengineered biomaterials offer a solution by solidifying and nanosizing these soluble regulating molecules and ions, facilitating their uptake by stem cells. Once inside lysosomes, these nanoparticles release their contents in a controlled “molecule or ion storm,” efficiently altering the intracellular biological and chemical microenvironment to tune the differentiation of stem cells. This newly emerged approach for regulating stem cell fate has attracted much attention in recent years. This method has shown promising results and is poised to enhance clinical stem cell therapy. This review provides an overview of the design principles for nanoengineered biomaterials, discusses the categories and characteristics of nanoparticles, summarizes the application of nanoparticles in tissue repair and regeneration, and discusses the direction of nanoparticle‐enhanced stem cell therapy and prospects for its clinical application in regenerative medicine.
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Affiliation(s)
- Yingxue Wang
- Institute for Advanced Interdisciplinary Research (iAIR) University of Jinan Jinan 250022 P. R. China
| | - Chunhui Sun
- Institute for Advanced Interdisciplinary Research (iAIR) University of Jinan Jinan 250022 P. R. China
| | - Zhaoying Liu
- Institute for Advanced Interdisciplinary Research (iAIR) University of Jinan Jinan 250022 P. R. China
| | - Shengmin Zhang
- Institute for Advanced Interdisciplinary Research (iAIR) University of Jinan Jinan 250022 P. R. China
| | - Ke Gao
- Institute for Advanced Interdisciplinary Research (iAIR) University of Jinan Jinan 250022 P. R. China
| | - Fan Yi
- School of Basic Medical Sciences Shandong University Jinan 250012 P. R. China
| | - Wenjuan Zhou
- School of Basic Medical Sciences Shandong University Jinan 250012 P. R. China
| | - Hong Liu
- Institute for Advanced Interdisciplinary Research (iAIR) University of Jinan Jinan 250022 P. R. China
- State Key Laboratory of Crystal Materials Shandong University Jinan 250100 P. R. China
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Han Y, Dong Y, Jia B, Shi X, Zhao H, Li S, Wang H, Sun B, Yin L, Dai K. High-precision bioactive scaffold with dECM and extracellular vesicles targeting 4E-BP inhibition for cartilage injury repair. Mater Today Bio 2024; 27:101114. [PMID: 39211509 PMCID: PMC11360177 DOI: 10.1016/j.mtbio.2024.101114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 05/13/2024] [Accepted: 06/06/2024] [Indexed: 09/04/2024] Open
Abstract
The restoration of cartilage injuries remains a formidable challenge in orthopedics, chiefly attributed to the absence of vascularization and innervation in cartilage. Decellularized extracellular matrix (dECM) derived from cartilage, following antigenic removal through decellularization processes, has exhibited remarkable biocompatibility and bioactivity, rendering it a viable candidate for cartilage repair. Additionally, extracellular vesicles (EVs) generated from cartilage have demonstrated a synergistic effect when combined with dECM, potentially mitigating the inhibitory impact on protein synthesis by phosphorylating 4ebp, thereby promoting the synthesis of cartilage-related proteins such as collagen. In pursuit of this objective, we have innovated a novel bioink and repair scaffold characterized by exceptional biocompatibility, bioactivity, and biodegradability, establishing a tissue-specific microenvironment conducive to chondrogenesis. Within rat osteochondral defects, the biologically active scaffold successfully prompted the formation of transparent cartilage, featuring adequate mechanical strength, favorable elasticity, and dECM deposition indicative of cartilage. In summary, this study has effectively engineered a hydrogel bioink tailored for cartilage repair and devised a bioactive cartilage repair scaffold proficient in instigating cell differentiation and fostering cartilage repair.
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Affiliation(s)
- Yu Han
- Department of Orthopaedics, Medical 3D Printing Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Department of Orthopedic Surgery, Shanghai Key Laboratory of Orthopedic Implants,Clinical and Translational Research Center for 3D Printing Technology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Yixin Dong
- Department of Orthopaedics, Medical 3D Printing Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Bo Jia
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
| | - Xiangyu Shi
- Department of Orthopaedics, Medical 3D Printing Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Hongbo Zhao
- Department of Orthopaedics, Medical 3D Printing Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Shushan Li
- Department of Orthopaedics, Medical 3D Printing Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Haitao Wang
- Department of Orthopaedics, Medical 3D Printing Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Binbin Sun
- Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, China
| | - Li Yin
- Department of Orthopaedics, Medical 3D Printing Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Kerong Dai
- Department of Orthopedic Surgery, Shanghai Key Laboratory of Orthopedic Implants,Clinical and Translational Research Center for 3D Printing Technology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
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Wang J, Gu Y, Sun Y, Qiao Q, Huang X, Yang K, Bai Y. Adipogenic differentiation effect of human periodontal ligament stem cell initial cell density on autologous cells and human bone marrow stromal cells. Cell Biochem Funct 2024; 42:e4069. [PMID: 38940455 DOI: 10.1002/cbf.4069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 05/22/2024] [Accepted: 05/23/2024] [Indexed: 06/29/2024]
Abstract
Stem cells demonstrate differentiation and regulatory functions. In this discussion, we will explore the impacts of cell culture density on stem cell proliferation, adipogenesis, and regulatory abilities. This study aimed to investigate the impact of the initial culture density of human periodontal ligament stem cells (hPDLSCs) on the adipogenic differentiation of autologous cells. Our findings indicate that the proliferation rate of hPDLSCs increased with increasing initial cell density (0.5-8 × 104 cells/cm2). After adipogenic differentiation induced by different initial cell densities of hPDLSC, we found that the mean adipose concentration and the expression levels of lipoprotein lipase (LPL), CCAAT/enhancer binding protein α (CEBPα), and peroxisome proliferator-activated receptor γ (PPAR-γ) genes all increased with increasing cell density. To investigate the regulatory role of hPDLSCs in the adipogenic differentiation of other cells, we used secreted exocrine vesicles derived from hPDLSCs cultivated at different initial cell densities of 50 μg/mL to induce the adipogenic differentiation of human bone marrow stromal cells. We also found that the mean adipose concentration and expression of LPL, CEBPα, and PPARγ genes increased with increasing cell density, with an optimal culture density of 8 × 104 cells/cm2. This study provides a foundation for the application of adipogenic differentiation in stem cells.
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Affiliation(s)
- Jing Wang
- Department of Orthodontics, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China
| | - Yingzhi Gu
- Department of Orthodontics, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China
| | - Yaxi Sun
- Department of Orthodontics, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China
| | - Qingchen Qiao
- Department of Orthodontics, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China
| | - Xiaofeng Huang
- Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Kai Yang
- Department of Orthodontics, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China
| | - Yuxing Bai
- Department of Orthodontics, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China
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Xu Y, Huang L, Zhuang Y, Huang H. Modulation of adipose tissue metabolism by exosomes in obesity. Am J Physiol Endocrinol Metab 2024; 326:E709-E722. [PMID: 38416071 DOI: 10.1152/ajpendo.00155.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 02/14/2024] [Accepted: 02/17/2024] [Indexed: 02/29/2024]
Abstract
Obesity and its related metabolic complications represent a significant global health challenge. Central to this is the dysregulation of glucolipid metabolism, with a predominant focus on glucose metabolic dysfunction in the current research, whereas adipose metabolism impairment garners less attention. Exosomes (EXs), small extracellular vesicles (EVs) secreted by various cells, have emerged as important mediators of intercellular communication and have the potential to be biomarkers, targets, and therapeutic tools for diverse diseases. In particular, EXs have been found to play a role in adipose metabolism by transporting cargoes such as noncoding RNAs (ncRNA), proteins, and other factors. This review article summarizes the current understanding of the role of EXs in mediating adipose metabolism disorders in obesity. It highlights their roles in adipogenesis (encompassing adipogenic differentiation and lipid synthesis), lipid catabolism, lipid transport, and white adipose browning. The insights provided by this review offer new avenues for developing exosome-based therapies to treat obesity and its associated comorbidities.
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Affiliation(s)
- Yajing Xu
- Department of Endocrinology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, People's Republic of China
| | - Linghong Huang
- Department of Endocrinology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, People's Republic of China
| | - Yong Zhuang
- Department of Endocrinology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, People's Republic of China
| | - Huibin Huang
- Department of Endocrinology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, People's Republic of China
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Liu M, Ng M, Phu T, Bouchareychas L, Feeley BT, Kim HT, Raffai RL, Liu X. Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes. Stem Cell Res Ther 2023; 14:321. [PMID: 37936229 PMCID: PMC10631219 DOI: 10.1186/s13287-023-03555-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 10/30/2023] [Indexed: 11/09/2023] Open
Abstract
BACKGROUND Macrophage polarization has been observed in the process of muscle injuries including rotator cuff (RC) muscle atrophy and fatty infiltration after large tendon tears. In our previous study, we showed that fibrogenesis and white adipogenesis of muscle residential fibro/adipogenic progenitors (FAPs) cause fibrosis and fatty infiltration and that brown/beige adipogenesis of FAPs promotes rotator cuff muscle regeneration. However, how polarized macrophages and their exosomes regulate FAP differentiation remains unknown. METHODS We cultured FAPs with M0, M1, and M2 macrophages or 2 × 109 exosomes derived from M0, M1 and M2 with and without GW4869, an exosome inhibitor. In vivo, M0, M1, and M2 macrophages were transplanted or purified macrophage exosomes (M0, M1, M2) were injected into supraspinatus muscle (SS) after massive tendon tears in mice (n = 6). SS were harvested at six weeks after surgery to evaluate the level of muscle atrophy and fatty infiltration. RESULTS Our results showed that M2 rather than M0 or M1 macrophages stimulates brown/beige fat differentiation of FAPs. However, the effect of GW4869, the exosome inhibitor, diminished this effect. M2 exosomes also promoted FAP Beige differentiation in vitro. The transplantation of M2 macrophages reduced supraspinatus muscle atrophy and fatty infiltration. In vivo injections of M2 exosomes significantly reduced muscle atrophy and fatty infiltration in supraspinatus muscle. CONCLUSION Results from our study demonstrated that polarized macrophages directly regulated FAP differentiation through their exosomes and M2 macrophage-derived exosomes may serve as a novel treatment option for RC muscle atrophy and fatty infiltration.
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Affiliation(s)
- Mengyao Liu
- Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, 94158, USA
- Department of Orthopedic Surgery, University of California, San Francisco, 1700 Owens Street, San Francisco, CA, 94158, USA
- College of Medicine, California Northstate University, Elk Grove, CA, 95757, USA
| | - Martin Ng
- Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, 94158, USA
- Department of Surgery, Division of Endovascular and Vascular Surgery, University of California, San Francisco, 4150 Clement Street, San Francisco, CA, 94121, USA
| | - Tuan Phu
- Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, 94158, USA
- Department of Surgery, Division of Endovascular and Vascular Surgery, University of California, San Francisco, 4150 Clement Street, San Francisco, CA, 94121, USA
| | - Laura Bouchareychas
- Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, 94158, USA
- Department of Surgery, Division of Endovascular and Vascular Surgery, University of California, San Francisco, 4150 Clement Street, San Francisco, CA, 94121, USA
| | - Brian T Feeley
- Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, 94158, USA
- Department of Orthopedic Surgery, University of California, San Francisco, 1700 Owens Street, San Francisco, CA, 94158, USA
| | - Hubert T Kim
- Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, 94158, USA
- Department of Orthopedic Surgery, University of California, San Francisco, 1700 Owens Street, San Francisco, CA, 94158, USA
| | - Robert L Raffai
- Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, 94158, USA.
- Department of Surgery, Division of Endovascular and Vascular Surgery, University of California, San Francisco, 4150 Clement Street, San Francisco, CA, 94121, USA.
| | - Xuhui Liu
- Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, 94158, USA.
- Department of Orthopedic Surgery, University of California, San Francisco, 1700 Owens Street, San Francisco, CA, 94158, USA.
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Zhou JQ, Wan HY, Wang ZX, Jiang N. Stimulating factors for regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells. World J Stem Cells 2023; 15:369-384. [PMID: 37342227 PMCID: PMC10277964 DOI: 10.4252/wjsc.v15.i5.369] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Revised: 02/21/2023] [Accepted: 03/29/2023] [Indexed: 05/26/2023] Open
Abstract
Mesenchymal stem cells (MSCs), distributed in many tissues in the human body, are multipotent cells capable of differentiating in specific directions. It is usually considered that the differentiation process of MSCs depends on specialized external stimulating factors, including cell signaling pathways, cytokines, and other physical stimuli. Recent findings have revealed other underrated roles in the differentiation process of MSCs, such as material morphology and exosomes. Although relevant achievements have substantially advanced the applicability of MSCs, some of these regulatory mechanisms still need to be better understood. Moreover, limitations such as long-term survival in vivo hinder the clinical application of MSCs therapy. This review article summarizes current knowledge regarding the differentiation patterns of MSCs under specific stimulating factors.
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Affiliation(s)
- Jia-Qi Zhou
- Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Hao-Yang Wan
- Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Zi-Xuan Wang
- Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Nan Jiang
- Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
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Wang F, Wang Q, Zhao Y, Tian Z, Chang S, Tong H, Liu N, Bai S, Li X, Fan J. Adipose-derived stem cells with miR-150-5p inhibition laden in hydroxyapatite/tricalcium phosphate ceramic powders promote osteogenesis via regulating Notch3 and activating FAK/ERK and RhoA. Acta Biomater 2023; 155:644-653. [PMID: 36206975 DOI: 10.1016/j.actbio.2022.09.070] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 09/24/2022] [Accepted: 09/28/2022] [Indexed: 02/02/2023]
Abstract
Adipose-derived mesenchymal stem cells (ADSCs) are multipotent stromal cells and play huge role in forming and repairing bone tissues. Emerging evidence shows that MicroRNAs (miRNAs) are involved in ADSCs differentiation. Here, we explored the role of miR-150-5p and its related mechanisms in ADSCs osteogenesis. Real-time PCR was used to determine miR-150-5p expression during ADSCs osteogenesis. miR-150-5p inhibitors, miR-150-5p ADV or short hairpin RNA (shRNA) of Notch3 were transfected to ADSCs for analyzing the effects on osteogenesis. The mixture of hydroxyapatite/tricalcium phosphate (HA/TCP) ceramic powders and transfected ADSCs was implanted into BALB/C nude mice. Micro-CT and histological methods were performed to evaluate the new bone formation. Compared with negative control (NC) and miR-150-5p overexpression, inhibition of miR-150-5p increased ADSCs osteogenesis by regulating Notch3. MiR-150-5p overexpression decreased the expression of pFAK, pERK1/2, and RhoA, while these were up-regulated when miR-150-5p was inhibited, or notch3 was silenced. Furthermore, miR-150-5p inhibition partially reversed the suppression effect of notch3 knockdown on osteogenesis in vitro and in vivo. This study demonstrated the critical function of miR-150-5p during osteogenesis. The combination of ADSCs with miR-150-5p inhibition and HA/TCP might be a promising strategy for bone damage repair. STATEMENT OF SIGNIFICANCE: Osteoporosis is a common chronic metabolic bone disease in humans. Bone tissue engineering based on mesenchymal stem cells, biomaterials, and growth factors, provides a promising way to treat osteoporosis and bone defects. ADSCs commonly differentiate into adipose cells, they can also differentiate into osteogenic cell lineages. Nucleic acids and protein have usually been considered as regulators of ADSCs osteogenic differentiation. In the current study, we demonstrated the combination of ADSCs with miR-150-5p inhibition and hydroxyapatite/tricalcium phosphate ceramic powders enhanced bone regeneration. Furthermore, miR-150-5p/Notch3 axis regulating osteogenesis via the FAK/ERK1/2 and RhoA pathway was assessed. The current study showed the application of ADSCs in bone regeneration might be a promising strategy for osteoporosis and bone damage repairing.
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Affiliation(s)
- Fanglin Wang
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China
| | - Qiao Wang
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China
| | - Yu Zhao
- Department of Plastic Surgery, Shengjing Hospital, Affiliated Hospital of China Medical University, No.36 Sanhao Street, Heping area, Shenyang, Liaoning 110004, PR China
| | - Zhiyu Tian
- Clinical Primary Department 105K, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China
| | - Shijie Chang
- Division of Biomedical Engineering, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China
| | - Hao Tong
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China
| | - Ningwei Liu
- 5+3 Integration of Clinical Medicine 106K, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China
| | - Shuling Bai
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China
| | - Xiang Li
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China; Department of Cell Biology, School of Life Sciences, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China.
| | - Jun Fan
- Department of Tissue Engineering, School of Intelligent Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China.
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Peruzzi B, Urciuoli E, Mariani M, Chioma L, Tomao L, Montano I, Algeri M, Luciano R, Fintini D, Manco M. Circulating Extracellular Vesicles Impair Mesenchymal Stromal Cell Differentiation Favoring Adipogenic Rather than Osteogenic Differentiation in Adolescents with Obesity. Int J Mol Sci 2022; 24:447. [PMID: 36613885 PMCID: PMC9820591 DOI: 10.3390/ijms24010447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/20/2022] [Accepted: 12/21/2022] [Indexed: 12/29/2022] Open
Abstract
Excess body weight has been considered beneficial to bone health because of its anabolic effect on bone formation; however, this results in a poor quality bone structure. In this context, we evaluated the involvement of circulating extracellular vesicles in the impairment of the bone phenotype associated with obesity. Circulating extracellular vesicles were collected from the plasma of participants with normal weight, as well as overweight and obese participants, quantified by flow cytometry analysis and used to treat mesenchymal stromal cells and osteoblasts to assess their effect on cell differentiation and activity. Children with obesity had the highest amount of circulating extracellular vesicles compared to controls. The treatment of mesenchymal stromal cells with extracellular vesicles from obese participants led to an adipogenic differentiation in comparison to vesicles from controls. Mature osteoblasts treated with extracellular vesicles from obese participants showed a reduction in differentiation markers in comparison to controls. Children with obesity who regularly performed physical exercise had a lower circulating extracellular vesicle amount in comparison to those with a sedentary lifestyle. This pilot study demonstrates how the high amount of circulating extracellular vesicles in children with obesity affects the bone phenotype and that physical activity can partially rescue this phenotype.
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Affiliation(s)
- Barbara Peruzzi
- Research Area for Multifactorial Diseases and Complex Phenotypes, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
| | - Enrica Urciuoli
- Research Area for Multifactorial Diseases and Complex Phenotypes, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
| | - Michela Mariani
- Unit of Endocrinology, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
| | - Laura Chioma
- Unit of Endocrinology, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
| | - Luigi Tomao
- Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
| | - Ilaria Montano
- Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
| | - Mattia Algeri
- Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
| | - Rosa Luciano
- Department of Laboratory Medicine, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
| | - Danilo Fintini
- Unit of Endocrinology, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
| | - Melania Manco
- Unit of Endocrinology, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
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10
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Analysis of the different characteristics between omental preadipocytes and differentiated white adipocytes using bioinformatics methods. Adipocyte 2022; 11:227-238. [PMID: 35499169 PMCID: PMC9067510 DOI: 10.1080/21623945.2022.2063471] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Obesity is emerging as an epidemiological issue, being associated with the onset and progress of various metabolism-related disorders. Obesity is characterized by the white adipose expansion, which encounters white adipocyte hypertrophy and hyperplasia. White adipocyte hyperplasia is defined as adipogenesis with the increase in the number of the white adipocytes from the preadipocytes. Adipogenesis contributes to distributing excess triglycerides among the smaller newly formed adipocytes, reducing the number of hypertrophic adipocytes and secreting anti-inflammatory factor. Therefore, adipogenesis is emerging as a new therapeutic target for the treatment of obesity. In the present study, for a better understanding of the contribution of the alteration of the omental differentiated white adipocytes to the systemic metabolic disorders, we downloaded the mRNA expression profiles from GEO database GSE1657, 328 differentially expressed genes (DEGs) were screened between the undifferentiated preadipocytes (UNDIF) and omental differentiated white adipocytes (DIF). The contributions of the upregulated and downregulated DEGs to the system were performed via the Gene Ontology (GO) analysis, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Protein-Protein Interaction (PPI) network, respectively. The potential contribution of the whole altered genes in the differentiated white adipocytes was explored with the performance of Gene Set Enrichment Analysis (GSEA), especially on the GO analysis, KEGG analysis, hallmark analysis, oncogenic analysis and related miRNA analysis. The output of the current study will shed light on the new targets for the treatment of obesity and obesity-related disorders.
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11
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Wang Z, Zhao Z, Gao B, Zhang L. Exosome mediated biological functions within skeletal microenvironment. Front Bioeng Biotechnol 2022; 10:953916. [PMID: 35935491 PMCID: PMC9355125 DOI: 10.3389/fbioe.2022.953916] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 06/29/2022] [Indexed: 12/02/2022] Open
Abstract
Exosomes are membranous lipid vesicles fused with intracellular multicellular bodies that are released into the extracellular environment. They contain bioactive substances, including proteins, RNAs, lipids, and cytokine receptors. Exosomes in the skeletal microenvironment are derived from a variety of cells such as bone marrow mesenchymal stem cells (BMSCs), osteoblasts, osteoclasts, and osteocytes. Their biological function is key in paracrine or endocrine signaling. Exosomes play a role in bone remodeling by regulating cell proliferation and differentiation. Genetic engineering technology combined with exosome-based drug delivery can therapy bone metabolic diseases. In this review, we summarized the pathways of exosomes derived from different skeletal cells (i.e., BMSCs, osteoblasts, osteocytes, and osteoclasts) regulate the skeletal microenvironment through proteins, mRNAs, and non-coding RNAs. By exploring the role of exosomes in the skeletal microenvironment, we provide a theoretical basis for the clinical treatment of bone-related metabolic diseases, which may lay the foundation to improve bone tumor microenvironments, alleviate drug resistance in patients.
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Affiliation(s)
- Zhikun Wang
- School of Kinesiology, Shanghai University of Sport, Shanghai, China
| | - Zhonghan Zhao
- School of Kinesiology, Shanghai University of Sport, Shanghai, China
| | - Bo Gao
- Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- *Correspondence: Bo Gao, ; Lingli Zhang,
| | - Lingli Zhang
- College of Athletic Performance, Shanghai University of Sport, Shanghai, China
- *Correspondence: Bo Gao, ; Lingli Zhang,
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12
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Liu Q. The emerging roles of exosomal long non-coding RNAs in bladder cancer. J Cell Mol Med 2022; 26:966-976. [PMID: 34981655 PMCID: PMC8831985 DOI: 10.1111/jcmm.17152] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 11/30/2021] [Accepted: 12/14/2021] [Indexed: 12/12/2022] Open
Abstract
Extracellular vesicles (EVs), especially exosomes, have been reported to play essential roles as extracellular messengers by transporting goods in various diseases, while their potential roles in bladder cancer (BC) still remain to be further studied. BC exhibits a high degree of chemoresistance and metastatic ability, which may be affected by cancer‐derived exosomes that carry proteins, lipids and RNA. To date, the most studied exosomal molecular cargo is long non‐coding RNA (lncRNA). Although there is increasing interest in its role and function, there is relatively little knowledge about it compared with other RNA transcripts. Nevertheless, in the past ten years, we have witnessed increasing interest in the role and function of lncRNA. For example, lncRNAs have been studied as potential biomarkers for the diagnosis of BC. They may play a role as a therapeutic target in precision medicine, but they may also be directly involved in the characteristics of tumour progression, such as metastasis, epithelial‐mesenchymal transition and drug resistance. Cancer cells are on chemotherapy acting. The function of lncRNA in various cancer exosomes has not yet been determined. In this review, we summarize the current studies about the prominent roles of exosomal lncRNAs in genome integrity, BC progression and carcinogenic features.
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Affiliation(s)
- Qiang Liu
- Department of Urology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China
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