Low Serum Cultured Adipose Tissue-Derived Stromal Cells Ameliorate Acute Kidney Injury in Rats

Acute kidney injury (AKI) is a fatal medical episode caused by sudden kidney damage or failure, leading to the death of patients within a few hours or days. Previous studies demonstrated that exosomes derived from various mesenchymal stem/stromal cells (MSC-exosomes) have positive effects on renal injuries in multiple experimental animal models of kidney diseases including AKI. However, the mass production of exosomes is a challenge not only in preclinical studies with large animals but also for successful clinical applications. In this respect, tangential flow filtration (TFF) is suitable for good manufacturing practice (GMP)-compliant large-scale production of high-quality exosomes. Until now, no studies have been reported on the use of TFF, but rather ultracentrifugation has been almost exclusively used, to isolate exosomes for AKI therapeutic application in preclinical studies. Here, we demonstrated the reproducible large-scale production of exosomes derived from adipose tissue-derived MSC (ASC-exosomes) using TFF and the lifesaving effect of the ASC-exosomes in a lethal model of cisplatin-induced rat AKI. Our results suggest the possibility of large-scale stable production of ASC-exosomes without loss of function and their successful application in life-threatening diseases.

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Therapeutic potential of extracellular vesicles secreted by adipose tissue-derived mesenchymal stromal cells in acute kidney injury induced by sepsis

Cytotherapy ◽

10.1016/s1465324921004552 ◽

2021 ◽

Vol 23 (5) ◽

pp. S114

Author(s):

C.M. Nogueira ◽

C.M. Barbosa ◽

C.M. da Silva ◽

F.D. Ornellas ◽

D.D. Ornellas ◽

...

Keyword(s):

Acute Kidney Injury ◽

Adipose Tissue ◽

Extracellular Vesicles ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Therapeutic Potential ◽

Kidney Injury

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Adipose tissue derived mesenchymal stem cell transplantation in the treatment of ischemia/reperfusion induced acute kidney injury in rats. Application route and therapeutic window

Acta Cirurgica Brasileira ◽

10.1590/s0102-865020180110000008 ◽

2018 ◽

Vol 33 (11) ◽

pp. 1016-1026 ◽

Cited By ~ 4

Author(s):

Betânia Souza Monteiro ◽

Bianka Souza dos Santos ◽

Bruna Lopes de Almeida ◽

Emy Hiura ◽

Wagner Alexey Back Fiorio ◽

...

Keyword(s):

Acute Kidney Injury ◽

Adipose Tissue ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Therapeutic Window ◽

Mesenchymal Stem Cell Transplantation

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Association Between Serum Osmolality and Acute Kidney Injury in Critically Ill Patients: A Retrospective Cohort Study

Frontiers in Medicine ◽

10.3389/fmed.2021.745803 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jie Yang ◽

Yisong Cheng ◽

Ruoran Wang ◽

Bo Wang

Keyword(s):

Acute Kidney Injury ◽

Logistic Regression ◽

Critically Ill ◽

Critically Ill Patients ◽

Retrospective Cohort ◽

Kidney Injury ◽

High Serum ◽

Serum Osmolality ◽

Multivariate Logistic Regression ◽

Low Serum

Purposes: Acute kidney injury (AKI) is a common complication in critically ill patients and is usually associated with poor outcomes. Serum osmolality has been validated in predicting critically ill patient mortality. However, data about the association between serum osmolality and AKI is still lacking in ICU. Therefore, the purpose of the present study was to investigate the association between early serum osmolality and the development of AKI in critically ill patients.Methods: The present study was a retrospective cohort analysis based on the medical information mart for intensive care III (MIMIC-III) database. 20,160 patients were involved in this study and divided into six subgroups according to causes for ICU admission. The primary outcome was the incidence of AKI after ICU admission. The association between early serum osmolality and AKI was explored using univariate and multivariate logistic regression analyses.Results: The normal range of serum osmolality was 285–300 mmol/L. High serum osmolality was defined as serum osmolality >300 mmol/L and low serum osmolality was defined as serum osmolality <285 mmol/L. Multivariate logistic regression indicated that high serum osmolality was independently associated with increased development of AKI with OR = 1.198 (95% CL = 1.199–1.479, P < 0.001) and low serum osmolality was also independently associated with increased development of AKI with OR = 1.332 (95% CL = 1.199–1.479, P < 0.001), compared with normal serum osmolality, respectively.Conclusions: In critically ill patients, early high serum osmolality and low serum osmolality were both independently associated with an increased risk of development of AKI.

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Single Cell Profiling of Acute Kidney Injury Reveals Novel Transcriptional Signatures, Mixed Identities and Epithelial-to-Stromal Crosstalk

10.1101/2019.12.30.890905 ◽

2019 ◽

Author(s):

Valeria Rudman-Melnick ◽

Mike Adam ◽

Andrew Potter ◽

Saagar M. Chokshi ◽

Qing Ma ◽

...

Keyword(s):

Acute Kidney Injury ◽

Single Cell ◽

Stromal Cells ◽

Gene Activation ◽

Kidney Injury ◽

Rapid Decline ◽

Renal Tubules ◽

Developmental Gene ◽

Single Cell Profiling

SummaryAcute kidney injury (AKI) is a rapid decline of renal function, with an incidence of up to 67% of intensive care unit patients. Current treatments are merely supportive, emphasizing the need for deeper understanding that could lead to improved therapies. We used single cell RNA sequencing, in situ hybridization and protein expression analyses to create comprehensive renal cell specific transcriptional profiles of multiple AKI stages. We revealed that AKI induces marked dedifferentiation, renal developmental gene activation and mixed identities in injured renal tubules. Moreover, we identified potential pathologic crosstalk between epithelial and stromal cells, and several novel genes involved in AKI. We also demonstrated the definitive effects of age on AKI outcome, and showed that renal developmental genes hold a potential as novel AKI markers. Moreover, our study provides the resource power which will aid in unraveling the molecular genetics of AKI.

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Chronic Kidney Disease-Associated Inflammation Increases the Risks of Acute Kidney Injury and Mortality after Cardiac Surgery

International Journal of Molecular Sciences ◽

10.3390/ijms21249689 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9689

Author(s):

Angela Casas ◽

Adrián Mallén ◽

Arnau Blasco-Lucas ◽

Fabrizio Sbraga ◽

Jordi Guiteras ◽

...

Keyword(s):

Acute Kidney Injury ◽

Adipose Tissue ◽

Cardiac Surgery ◽

Coronary Artery ◽

Map Kinases ◽

Kidney Diseases ◽

Bypass Graft ◽

Kidney Injury ◽

Perivascular Adipose Tissue ◽

Increased Risk

Cardiovascular mortality increases with decreasing renal function although the cause is yet unknown. Here, we have investigated whether low chronic inflammation in chronic kidney diseases (CKD) could contribute to increased risk for coronary artery diseases (CAD). Thus, a prospective case–control study was conducted in patients with CAD and CKD undergoing coronary artery bypass graft surgery with the aim of detecting differences in cardiovascular outcomes, epicardial adipose tissue volume, and inflammatory marker activity associated with renal dysfunction. Expression of membrane CD14 and CD16, inflammatory cytokines and chemokines, mitogen-activated protein (MAP) kinases and hsa-miR-30a-5p were analyzed in peripheral blood mononuclear cells (PBMCs). Epicardial fat volume and tissue inflammation in perivascular adipose tissue and in the aorta were also studied. In the present study, 151 patients were included, 110 with CAD (51 with CKD) and 41 nonCAD controls (15 with CKD). CKD increased the risk of cardiac surgery–associated acute kidney injury (CSA-AKI) as well as the 30-day mortality after cardiac surgery. Higher counts of CD14++CD16+ monocytes were associated with vascular inflammation, with an increased expression of IL1β, and with CKD in CAD patients. Expression of hsa-miR-30a-5p was correlated with hypertension. We conclude that CKD patients show an increased risk of CSA-AKI and mortality after cardiovascular surgery, associated with the expansion of the CD14++CD16+ subset of proinflammatory monocytes and with IL1β expression. We propose that inflammation associated with CKD may contribute to atherosclerosis (ATH) pathogenesis.

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