Administration of mesenchymal stem cells in diabetic kidney disease: mechanisms, signaling pathways, and preclinical evidence

Zhu, Yongtong; Luo, Manyu; Bai, Xue; Lou, Yan; Nie, Ping; Jiang, Shan; Li, Jicui; Li, Bing; Luo, Ping

doi:10.1007/s11010-022-04421-4

Cited by 7 publications

(5 citation statements)

References 155 publications

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“…A clinical trial has tried a single intravenous injection of ADSCs to treat 30 patients with DN for three months, and the outcomes showed recovery of renal function with little adverse event [ 31 ]. However, the comprehensive evaluation of the efficacy, tolerability, and safety of MSCs in the treatment of DN is still lacking [ 32 ]. Therefore, this study conducted evaluation of the concrete efficacy and mechanism of hucMSCs in the treatment of DN by applying in vivo (STZ-induced diabetic rats) and in vitro (high glucose-induced rat podocytes) models.…”

Section: Discussionmentioning

confidence: 99%

Intravenous injection of human umbilical cord-derived mesenchymal stem cells ameliorates not only blood glucose but also nephrotic complication of diabetic rats through autophagy-mediated anti-senescent mechanism

Guo

Chen

et al. 2023

Stem Cell Res Ther

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Background Diabetic nephropathy (DN) is one of the most severe complications of diabetes mellitus, which is characterized by early occurrence of albuminuria and end-stage glomerulosclerosis. Senescence and autophagy of podocytes play an important role in DN development. Human umbilical cord-derived mesenchymal stem cells (hucMSCs) have potential in the treatment of diabetes and its complications. However, the role of hucMSCs in the treatment of DN and the underlying mechanism remain unclear. Methods In vivo, a streptozotocin-induced diabetic male Sprague Dawley rat model was established to determine the renoprotective effect of hucMSCs on DN by biochemical analysis, histopathology, and immunohistochemical staining of renal tissues. And the distribution of hucMSCs in various organs in rats within 168 h was analyzed. In vitro, CCK8 assay, wound healing assay, and β-galactosidase staining were conducted to detect the beneficial effects of hucMSCs on high glucose-induced rat podocytes. Real-time PCR and western blot assays were applied to explore the mechanism of action of hucMSCs. Results The in vivo data revealed that hucMSCs were distributed into kidneys and significantly protected kidneys from diabetic damage. The in vitro data indicated that hucMSCs improved cell viability, wound healing, senescence of the high glucose-damaged rat podocytes through a paracrine action mode. Besides, the altered expressions of senescence-associated genes (p16, p53, and p21) and autophagy-associated genes (Beclin-1, p62, and LC3) were improved by hucMSCs. Mechanistically, hucMSCs protected high glucose-induced injury in rat podocytes by activating autophagy and attenuating senescence through the AMPK/mTOR pathway. Conclusions In conclusion, hucMSCs might be a promising therapeutic strategy for the clinical treatment of DN-induced renal damages.

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Section: Discussionmentioning

confidence: 99%

Intravenous injection of human umbilical cord-derived mesenchymal stem cells ameliorates not only blood glucose but also nephrotic complication of diabetic rats through autophagy-mediated anti-senescent mechanism

Guo

Chen

et al. 2023

Stem Cell Res Ther

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“…The interference by MSC-Exos with TLR signaling and its subsequent downstream cascades leads to the suppression of JAK/STAT activation. 103,104 The JAK/STAT pathway activation encompasses the phospho- and critical TLR and NLR cascade components. By downregulating these molecules, miR-155 limits the activation of these receptors and their downstream pro-inflammatory responses.…”

Section: Jak/stat Signaling Pathwaymentioning

confidence: 99%

“…The control of the JAK/STAT signaling pathway by MSC‐Exos through PRRs, encompassing TLRs and NLRs, assumes a pivotal function in immunomodulation 102 ; this involves the mechanisms through which MSC‐Exos impacts the JAK/STAT pathway via TLRs and NLRs: Inhibition of TLR‐mediated JAK/STAT activation: The activation of TLRs can initiate the JAK/STAT signaling pathway. The interference by MSC‐Exos with TLR signaling and its subsequent downstream cascades leads to the suppression of JAK/STAT activation 103,104 …”

Section: Regulation Of Prrs‐mediating Signaling Pathways By Mscs‐deri...mentioning

confidence: 99%

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A comprehensive insight into the immunomodulatory role of MSCs‐derived exosomes (MSC‐Exos) through modulating pattern‐recognition receptors (PRRs)

Alshahrani,

Jasim,

Altalbawy

et al. 2024

Cell Biochemistry & Function

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Mesenchymal stem cell‐derived exosomes (MSC‐Exos) are emerging as remarkable agents in the field of immunomodulation with vast potential for diagnosing and treating various diseases, including cancer and autoimmune disorders. These tiny vesicles are laden with a diverse cargo encompassing proteins, nucleic acids, lipids, and bioactive molecules, offering a wealth of biomarkers and therapeutic options. MSC‐Exos exhibit their immunomodulatory prowess by skillfully regulating pattern‐recognition receptors (PRRs). They conduct a symphony of immunological responses, modulating B‐cell activities, polarizing macrophages toward anti‐inflammatory phenotypes, and fine‐tuning T‐cell activity. These interactions have profound implications for precision medicine, cancer immunotherapy, autoimmune disease management, biomarker discovery, and regulatory approvals. MSC‐Exos promises to usher in a new era of tailored therapies, personalized diagnostics, and more effective treatments for various medical conditions. As research advances, their transformative potential in healthcare becomes increasingly evident.

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“…DKD is the main cause of end-stage renal disease (ESRD) worldwide, affecting approximately 30% of patients with type 1 DM and approximately 40% of patients with type 2 DM, as reviewed elsewhere ( 4 ). DKD is clinically characterized by increased urinary albumin excretion and reduced renal function ( 5 ). Clinical diagnosis of DKD is usually based on microalbuminuria (30-300 mg/day) or the urinary albumin/creatinine ratio (>30 mg/g creatinine) ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Proteomic profiling and correlations with clinical features reveal biomarkers indicative of diabetic retinopathy with diabetic kidney disease

Fan

Xu²,

Chen³

et al. 2022

Front. Endocrinol.

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Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are complications of diabetes and place serious health and economic burdens on society. However, the identification and characterization of early biomarkers for DKD, especially for nonproliferative DR (NPDR) patients with DKD, are still needed. This study aimed to demonstrate the plasma proteomic profiles of NPDR+DKD and NPDR patients and identify potential biomarkers for early diagnosis of DKD. Fifteen plasma samples from the NPDR group and nine from the NPDR+DKD group were analyzed by LC−MS/MS to identify the differentially expressed proteins between the two groups. Functional enrichment, protein−protein interaction and clinical feature correlation analyses revealed the target protein candidates, which were verified using ELISA and receiver operating characteristic (ROC) analysis. In total, 410 proteins were detected in plasma; 15 were significantly upregulated and 7 were downregulated in the NPDR+DKD group. Bioinformatics analysis suggested that DKD is closely related to cell adhesion and immunity pathways. β-2-Microglobulin (B2M) and vimentin (VIM) were upregulated in NPDR+DKD, enriched as hub proteins and strongly correlated with clinical features. ELISA showed that B2M (p<0.001) and VIM (p<0.0001) were significantly upregulated in NPDR+DKD compared with NPDR. In ROC analysis, B2M and VIM could distinguish DKD from NPDR with area under the curve values of 0.9000 (p < 0.0001) and 0.9950. Our proteomic study revealed alterations in the proteomic profile and identified VIM and B2M as early biomarkers of DKD, laying the foundation for the prevention, diagnosis and treatment of DKD.

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Administration of mesenchymal stem cells in diabetic kidney disease: mechanisms, signaling pathways, and preclinical evidence

Cited by 7 publications

References 155 publications

Intravenous injection of human umbilical cord-derived mesenchymal stem cells ameliorates not only blood glucose but also nephrotic complication of diabetic rats through autophagy-mediated anti-senescent mechanism

Intravenous injection of human umbilical cord-derived mesenchymal stem cells ameliorates not only blood glucose but also nephrotic complication of diabetic rats through autophagy-mediated anti-senescent mechanism

A comprehensive insight into the immunomodulatory role of MSCs‐derived exosomes (MSC‐Exos) through modulating pattern‐recognition receptors (PRRs)

Proteomic profiling and correlations with clinical features reveal biomarkers indicative of diabetic retinopathy with diabetic kidney disease

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