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EXPERIMENTAL BIOLOGY AND MEDICINE 2001年第6期226卷 507-520页

作者： Minguell, JJ Erices, A Conget, P Univ Chile INTA Unidad Biol Celular Santiago 11 Chile Clin Las Condes Lab Transplante Medula Osea Santiago Chile

Within the bone marrow stroma there exists a subset of nonhematopoietic cells referred to as mesenchymal stem or mesenchymal progenitor cells. These cells can be ex vivo expanded and induced, either in vitro or in vivo, to terminally differentiate into osteoblasts, chondrocytes, adipocytes, tenocytes, myotubes, neural cells, and hematopoietic-supporting stroma. The multipotential of these cells, their easy isolation and culture, as well as their high ex vivo expansive potential make these cells an attractive therapeutic tool. In this work we will review the information dealing with the biology of mesenchymal progenitors as it has been revealed mainly by ex vivo studies performed with bone marrow-derived cells. The discussed topics include, among others, characteristics of mesenchymal progenitors, evidence for the existence of a vast repertoire of uncommitted and committed progenitors both in the bone marrow and in mesenchymal tissues, a diagram for their proliferative hierarchy, and comments on mobilization, microenvironment, and clinical use of mesenchymal progenitors. Despite the enormous data available at molecular and cellular levels, it is evident that a number of fundamental questions still need to be resolved before mesenchymal progenitors can be used for safe and effective clinical applications in the context of both cell and gene therapies.

关键词： mesenchymal stem cells marrow stromal cells uncommitted mesenchymal progenitors human mesenchymal stem cells characteristics mesenchymal progenitors

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mesenchymal stem cells

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VOX SANGUINIS 2004年第Sup2期87卷 38-41页

作者： Roberts, I Univ London Imperial Coll Sci Technol & Med Dept Haematol London W12 0NN England

The article discusses on the nature and characteristics of mesenchymal stem cells (MSC). MSC are the spindle-shaped and it resembles fibroblast. Since MSC has no marker and can not be identified they are defined in its immunophenotypic profile. The most well studied and primary source of MSC is bone marrow, although this tissue cells are present in a low frequency. It has shown in recent work hat MSC are also present in fetal bone marrow from as early as 9 weeks gestation and prior to it they circulate in fetal blood in fairly high numbers from seven weeks gestation.

关键词： Animals Blood Component Removal Cell Differentiation Cytokines Hematopoiesis Hematopoietic stem Cell Transplantation Humans Immunophenotyping mesenchymal stem cells stem cells

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mesenchymal stem cells With Polydopamine-Coated NaGdF4 Nanoparticles with Ca²⁺ Chelation Ability for Ischemic Stroke Therapy

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ADVANCED MATERIALS 2025年第10期37卷 e2416020页

作者： Wu, Shiman Chu, Xu Lv, Guanglei Gao, Jiahao Huang, Yuxin Li, Huiyan Jiang, Xingwu Liu, Yanyan Zhang, Jiawen Fang, Xiangming Yao, Zhenwei Bu, Wenbo Fudan Univ Huashan Hosp Dept Radiol Shanghai 200040 Peoples R China Fudan Univ Dept Mat Sci Acad Engn & Technol Shanghai 200433 Peoples R China Fudan Univ Acad Engn & Technol State Key Lab Mol Engn Polymers Shanghai 200433 Peoples R China Nanjing Med Univ Affiliated Wuxi Peoples Hosp Dept Radiol Wuxi 214023 Jiangsu Peoples R China

mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for ischemic stroke. However, the survival of transplanted MSCs is often compromised by the excessive levels of reactive oxygen species (ROS) and calcium ions (Ca2+) in the ischemic microenvironment following blood flow occlusion. In this study, a protective strategy is developed using functional nanomaterials to escort and shield MSCs. Specifically, NaGdF4@PDA-ALD nanoparticles (NPANs) are synthesized, featuring a NaGdF4 core coated with polydopamine (PDA) for ROS scavenging and further modified with alendronate sodium (ALD) for Ca2+ chelation. The internalization of NPANs by MSCs protected them from oxidative damage and calcium overload, thereby promoting their viability and functionality. Furthermore, NaGdF4 generated T-1 signal enhancement, enabling in vivo tracking of MSCs via magnetic resonance imaging. The NPANs-treated MSCs demonstrated improved survival and migration to the ischemic region, promoting blood flow restoration and angiogenesis. These findings confirm the feasibility of employing functional nanoparticles to augment MSCs-based therapies, offering a promising strategy to improve their therapeutic efficacy in ischemic stroke treatment.

关键词： calcium overload mesenchymal stem cells NaGdF4 nanoparticles reactive oxygen species stroke

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mesenchymal stem cells-Derived Extracellular Vesicles Mimetics as Osteoinductive Mediators for Bone Healing

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ADVANCED FUNCTIONAL MATERIALS 2025年第0期

作者： Karoichan, Antoine Li, Ling Agnes, Celine J. Willie, Bettina M. Tabrizian, Maryam McGill Univ Fac Dent Med & Oral Hlth Sci 2001 McGill Coll Ave Montreal PQ H3A 1G1 Canada Shriners Hosp Children 1003 Decarie Blvd Montreal PQ H4A 0A9 Canada McGill Univ Dept Biomed Engn 3775 Univ St Montreal PQ H3A 2B4 Canada

Bone defects remain challenging to treat, with common therapies still relying on invasive approaches. mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) offer a promising alternative due to their regenerative and immunomodulatory properties, but challenges in scalable EV production limit clinical translation. Nanoghosts (NGs) are an emerging class of EV-mimetics synthesized through the physical distortion of ghost cells that offer innate bioactivity similar to EVs while having more scalable yields. In this study, the osteogenic potential of NGs made from MSC ghosts (MSC-NGs) is explored for the first time and contrasted with conventional MSC-EVs. MSC-NGs are generated through sonication, yielding two-fold more vesicles compared to MSC-EVs from the same number of cells. Unlike MSC-EVs, MSC-NGs significantly enhanced the osteogenic differentiation of MSCs, evidenced by increased alkaline phosphatase (ALP) activity and early mineralization. Proteomic analysis further revealed that MSC-NGs are more enriched in osteogenesis-related proteins than MSC-EVs. In vivo, treatment of a 0.5 mm mouse femoral osteotomy with MSC-NGs accelerated fracture healing, showing increased callus mineralization by day 14 and improved bone marrow reconstitution by day 21, along with reduced osteoclastic activity. These findings demonstrate MSC-NGs as scalable and effective therapeutics for bone tissue engineering, offering advantages over MSC-EVs in future bone healing strategies.

关键词： bone healing EV-mimetics extracellular vesicles and nanoghosts mesenchymal stem cells osteogenic differentiation

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mesenchymal stem cells therapy for the treatment of non-union fractures: a systematic review and meta-analysis

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BMC MUSCULOSKELETAL DISORDERS 2025年第1期26卷 1-23页

作者： Cui, Cunbao Lin, Feng Xia, Liang Zhang, Xinguang Shandong First Med Univ Cent Hosp Dept Joint Surg 105 Jiefang Rd Jinan 250013 Peoples R China Shandong First Med Univ Cent Hosp Dept Thorac Surg 105 Jiefang Rd Jinan 250013 Peoples R China

BackgroundThis meta-analysis aimed to pool the existing evidence to determine the clinical efficacy and safety of mesenchymal stem cells (MSC) in patients with *** systematic search in PubMed and Scopus was performed until October 2024 to gather pertinent studies. The inclusion criteria included participants with non-unions, the intervention of MSC administration, a comparator of standard treatment (bone graft), and outcomes focused on healing rate, healing time, or side effects. The Jadad score Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias in randomized and non-randomized studies, respectively. Moreover, GRADE criteria were used to assess the quality of evidence. Using a random effects model, odds ratios (OR) with 95% confidence intervals (CIs) were calculated for healing and complication rates, while standardized mean differences (SMD) with their 95% CIs were used to assess the impact of MSC therapy on bone union ***-one studies, with 866 patients, were included. The bone healing rates were 44% at 3 months, 73% at 6 months, 90% at 9 months, and 86% at 12 months, eventually reaching 91% after 12 months of follow-up. MSC therapy, with or without scaffolds, was linked to higher odds of bone healing rate at 3 and 6 months, compared to bone grafts as the standard care (OR = 1.69). The time to union following the treatment was 6.30 months (95%CI: 86-96%), with patients treated with MSC/Scaffold experiencing a shorter time compared to MSC alone (5.85 vs. 6.36 months). MSC therapy significantly decreased bone union time (SMD:-0.54 months, 95% CI: -0.75 to -0.33). The complication rate was 1% (MSC/Scaffold: 0%, MSC alone: 2%), with MSC alone or MSC/Scaffold showing a lower risk than the standard care (OR = 0.41, 95% CI: 0.22-0.78).ConclusionMSC is a potential adjunct therapy for patients with non-union *** trial numberNot applicable.

关键词： mesenchymal stem cells MSCs Non-union Bone healing Meta-analysis

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mesenchymal stem cells attenuate hyperoxaluria-induced kidney injury and crystal depositions via inhibiting the activation of NLRP3 inflammasome

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LIFE SCIENCES 2025年 371卷 123608页

作者： Zou, Bangyu Wang, Ding Zhong, Jinghua He, Zhiqing Zhou, Yuhao Yang, Houmeng Liu, Yongda Zeng, Guohua Duan, Xiaolu Guangzhou Med Univ Affiliated Hosp 1 Dept Urol Guangzhou Peoples R China Guangdong Prov Key Lab Urol Dis Guangzhou Peoples R China Guangdong Engn Res Ctr Urinary Minimally Invas Sur Guangzhou Peoples R China Guangzhou Med Univ Guangzhou Inst Urol Guangzhou Peoples R China Guangzhou Med Univ Guangdong Prov Clin Res Ctr Obstet & Gynecol Dept Obstet & Gynecol Guangdong Prov Key Lab Major Obstet DisAffiliated Guangzhou Peoples R China Univ Chinese Acad Sci Hwa Mei Hosp Ningbo 2 Hosp Dept Urol Ningbo Peoples R China Naval Med Univ Changhai Hosp Affiliated Hosp 1 Dept Urol Shanghai Peoples R China

Aims: Calcium oxalate (CaOx) is the predominant form of kidney stones, associated with significant morbidity and recurrence rates. mesenchymal stem cells (MSCs) have shown promise in treating renal injury, but their impact on CaOx stone formation remains unclear. Materials and methods: We established a hyperoxaluria-induced AKI model in mice through intraperitoneal injection of glyoxylate. Two types of MSCs, bone marrow-derived MSCs (BMSCs) and umbilical cord-derived mesenchymal stem cells (UMSCs), were injected through tail vein injection. Histological evaluations and blood biochemical tests were performed to assess crystal deposition and kidney function. The inflammatory response and NLRP3 inflammasome activation were assessed using immunofluorescence, immunohistochemistry, TUNEL staining, and qPCR. In vitro, macrophages were cocultured in the presence of MSCs. ELISA was used to measure IL-1(3 and IL-18 release. MTS assays assessed renal epithelial cell protection. Western blotting evaluated NLRP3 inflammasome activation in macrophages. Key findings: Both BMSCs and UMSCs significantly inhibited CaOx crystal deposition and kidney injury by inhibiting NLRP3 inflammasome activation. In vitro, both MSC types suppressed NLRP3 inflammasome activation in macrophages through the NF-kappa B signaling pathway, leading to decreased release of IL-1(3 and IL-18 and enhanced protection of renal epithelial cells. This attenuation of renal tubular cell injury is a critical factor in preventing CaOx stone formation. Significance: Our findings reveal that Both BMSCs and UMSCs effectively attenuate hyperoxaluria-induced kidney injury and crystal deposition by inhibiting NLRP3 inflammasome activation. This discovery is helpful for developing new effective therapeutic means for nephrolithiasis.

关键词： mesenchymal stem cells Nephrolithiasis Kidney injury NLRP3 inflammasome

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mesenchymal stem cells-derived small extracellular vesicles and apoptotic extracellular vesicles for wound healing and skin regeneration: a systematic review and meta-analysis of preclinical studies

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JOURNAL OF TRANSLATIONAL MEDICINE 2025年第1期23卷 1-21页

作者： Zhu, Yufan Yang, Han Xue, Zhixin Tang, Haojing Chen, Xihang Liao, Yunjun Southern Med Univ Nanfang Hosp Dept Plast & Cosmet Surg 1838 Guangzhou North Rd Guangzhou 510515 Guangdong Peoples R China

BackgroundStudies examining the therapeutic potential of mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) in wound healing and skin regeneration have progressed rapidly. Prior to considering clinical translation, a systematic and comprehensive understanding of these experimental details and the overall impact of MSC-EVs on skin regeneration is ***83 studies were identified in Web of Science, Embase, and PubMed that satisfied a set of prespecified inclusion criteria. A random effects meta-analysis was conducted for wound closure rate, scar width, blood vessel density and collagen *** findings demonstrate clear potential of MSC-EVs to be developed as therapy for wound healing and skin regeneration both in diabetic and non-diabetic animal models. Moreover, subgroup analyses demonstrated that apoptotic small extracellular vesicles (ApoSEVs) showed better efficacy than apoptotic bodies (ApoBDs) and small extracellular vesicles (sEVs) in wound closure outcome and collagen deposition, while sEVs displayed better than ApoEVs in revascularization. Among frequently used routes of administration, subcutaneous injection displayed a greater improvement to wound closure, collagen deposition and revascularization as compared to dressing/covering. Among easier-access source of MSCs, ADSCs demonstrated the best effect in wound closure rate and collagen deposition, as compared, BMMSCs displayed better in revascularization. Additionally, high heterogeneity observed in collection conditions, separation methods, storage methods, modifications, treatment dose, administration route, and frequency of MSC-EVs underscores the urgent need for standardization in these areas, prior to clinical *** RegistrationPROSPERO CRD42024499172.

关键词： Extracellular vesicles mesenchymal stem cells Skin regeneration Wound healing Meta-analysis

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mesenchymal stem cells versus mesenchymal stem cells-derived exosomes as potential autophagy pathway modulators in a diabetic model

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ADVANCES IN MEDICAL SCIENCES 2025年第1期70卷 152-165页

作者： Meligy, Fatma Y. Mohammed, Hanan Sharaf El-Deen Elghait, Amal T. Abou Mohamed, Heba K. Ashry, Israa El-Sayed Mohamed Sayed, Ayat Abdel-Rahman Hussein, Ola A. Salman, Ahmed Atia, Tarek Mohamed, Abir S. Behnsawy, Nour H. Gaber, Safy Salah Sakr, Hader I. Ahmed, Salwa Fares Univ Petra Fac Dent Dept Restorat Dent & Basic Med Sci Amman Jordan Assiut Univ Fac Med Histol & Cell Biol Dept Assiut Egypt Assiut Univ Fac Med Internal Med Dept Crit Care Unit Assiut Egypt Sphinx Univ Histol & Cell Biol Dept Assiut Egypt Assiut Univ Anat & Embryol Dept Fac Med Assiut Egypt Sphinx Univ Assiut Assiut Egypt Assiut Univ Fac Med Pharmacol Dept Assiut Egypt Assiut Univ Fac Med Med Biochem Dept Assiut Egypt Sphinx Univ Dept Biochem Assiut Egypt Univ Jordan Fac Med Dept Anat & Histol Amman Jordan Menoufia Univ Fac Med Dept Anat & Embryol Menoufia Egypt Prince Sattam Bin Abdulaziz Univ Coll Appl Med Sci Dept Med Lab Al Kharj Saudi Arabia Jazan Univ Coll Nursing & Hlth Sci Dept Publ Hlth Jazan Saudi Arabia Assiut Univ Fac Med Assiut Egypt Univ Uberaba UNIUBE Cairo Brazil Beni Suef Univ Fac Med Dept Med Physiol Bani Suwayf Egypt Cairo Univ Fac Med Dept Med Physiol Cairo Egypt Batterjee Med Coll Dept Med Physiol Gen Med Practice Program Jeddah 21442 Saudi Arabia Univ Tabuk Fac Med Anat Dept Tabuk Saudi Arabia

Purpose: This work compared the potential effects of bone marrow mesenchymal stem cells (BM-MSCs) with BMMSCs-derived exosomes against impaired autophagy in streptozotocin (STZ)-induced diabetic rats. Materials and methods: Three days after STZ injection, a single dose of (3 x 10<^>6) BM- MSCs or BM-MSCs-derived exosomes (80 mu g/rat) was administered to evaluate their effects against nondiabetic and diabetic control rats. We assessed pancreatic structure via light and electron microscopy and evaluated its staining for insulin and the autophagy marker P62 immunohistochemically. Moreover, autophagy marker LC3 gene expression was examined by PCR. Results: Both BM-MSCs and BM-MSCs derived exosomes showed histological restoration of pancreatic tissues. Both treatments markedly increased the amount of insulin and significantly decreased the autophagy markers P62 and LC3. Conclusion: Our findings suggest that both BM-MSCs and BM-MSCs-derived exosomes provides a potential alternative to modulate diabetes mellitus.

关键词： Diabetes mellitus mesenchymal stem cells Exosome Autophagy

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mesenchymal stem cells derived exosomes: a new era in cardiac regeneration

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stem CELL RESEARCH & THERAPY 2025年第1期16卷 1-21页

作者： Pisheh, Hossein Rayat Sani, Mahsa Shiraz Univ Med Sci Sch Adv Med Sci & Technol Dept Tissue Engn & Appl Cell Sci Shiraz Iran Shiraz Univ Med Sci Shiraz Inst Stem Cell & Regenerat Med Shiraz Iran

Despite significant strides in medical treatments and surgical procedures for cardiovascular diseases, these conditions continue to be a major global health concern. The persistent need for innovative therapeutic approaches to mend damaged heart tissue highlights the complexity and urgency of this medical challenge. In recent years, stem cells have emerged as a promising tool for tissue regeneration, but challenges such as graft rejection and tumor formation have limited their clinical application. Exosomes, extracellular vesicles containing a diverse array of biomolecules, have garnered significant attention for their potential in regenerative medicine. The cardioprotective and reparative properties of mesenchymal stem cell-derived exosomes hold promise for the treatment of heart diseases. These exosomes can modulate various cellular processes, including angiogenesis, apoptosis, and inflammation, thereby enhancing cardiac function. Despite the growing interest, there remains a lack of comprehensive reviews synthesizing the molecular mechanisms, preclinical, and clinical evidence related to the specific role of MSC-derived exosomes in cardiac therapies. This review aims to fill that gap by exploring the potential of MSC-derived exosomes as a therapeutic strategy for cardiac diseases. This review explores the potential of mesenchymal stem cell-derived exosomes as a therapeutic strategy for cardiac diseases. We discuss the molecular mechanisms underlying their cardioprotective effects, summarize preclinical and clinical studies investigating their efficacy, and address the challenges and future perspectives of exosome-based therapies. The collective evidence suggests that MSC-derived exosomes hold promise as a novel and effective therapeutic approach for cardiac diseases.

关键词： Exosomes mesenchymal stem cells Cardiovascular diseases Tissue repair Angiogenesis

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mesenchymal stem cells and mesenchymal stem cell-derived exosomes: attractive therapeutic approaches for female reproductive dysfunction

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MOLECULAR BIOLOGY REPORTS 2025年第1期52卷 1-17页

作者： Khodaei, Sepideh Hassanpour Sabetkam, Shahnaz Kalarestaghi, Hossein Asl, Khadijeh Dizaji Mazloumi, Zeinab Bahramloo, Mohammadmahdi Norouzi, Nahid Naderali, Elahe Rafat, Ali Eastern Mediterranean Univ EMU Famagusta Dept Dent Mersin 10 Famagusta North Cyprus Turkiye Univ Kyrenia Fac Med Dept Anat Kyrenia Northern Cyprus Turkiye Ardabil Univ Med Sci Sch Med Dept Anat Sci Res Lab Embryol & Stem Cell Ardebil Iran Islamic Azad Univ Fac Med Sci Dept Histopathol & Anat Tabriz Med Sci Tabriz Iran Tabriz Univ Med Sci Fac Adv Med Sci Dept Med Appl Cell Sci Tabriz Iran Islamic Azad Univ Student Res Comm Dept Med Sci Tabriz Branch Tabriz Iran Kashan Univ Med Sci Nursing Trauma Res Ctr Kashan Iran Maragheh Univ Med Sci Dept Anat Sci Maragheh Iran Kashan Univ Med Sci Inst Basic Sci Anat Sci Res Ctr Kashan Iran

Infertility is a reproductive health problem in the male or female reproductive system. Traditional assisted reproductive technology (ART) has been unable to solve various cases of infertility for years. Clinical researchers have sought to treat infertility using new methods that are more effective and noninvasive than the old methods. Recently, mesenchymal stem cells (MSCs) and MSCs-derived Exosomes (MSC-Exos) via paracrine activity play an important role in treating various causes of infertility and improving pregnancy outcomes. In this review, we focus on the roles of MSCs and MSC-Exos cell therapy in female infertility in the different types of female reproductive disorders.

关键词： Reproductive diseases Infertility mesenchymal stem cells mesenchymal stem cell-derived exosomes

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