Mesenchymal stromal cell–based therapies for acute kidney injury: progress in the last decade

Fazekas, Barbara; Griffin, Matthew D.

doi:10.1016/j.kint.2019.12.019

Cited by 50 publications

(55 citation statements)

References 105 publications

(233 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further, MSCs may accelerate tissue repair via a paracrine mechanism leading to proangiogenic, anti‐inflammatory, and antifibrotic effects than directly differentiating into tissue‐specific cells (Gnecchi et al, 2005). Preclinical and clinical trials are in progress to evaluate the beneficial effects of MSC therapy in various kidney disease models (Fazekas & Griffin, 2020; Perico et al, 2018). However, it is imperative to consider that autologous cell transplantation is preferred over allogenic transplantation in patients with CKD who may need kidney transplantation in the future, as the latter may increase the risk of allosensitization.…”

Section: Introductionmentioning

confidence: 99%

Metformin inhibits chronic kidney disease‐induced DNA damage and senescence of mesenchymal stem cells

Kim

Yu²,

Lee

et al. 2021

Aging Cell

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) are promising source of cell‐based regenerative therapy. In consideration of the risk of allosensitization, autologous MSC‐based therapy is preferred over allogenic transplantation in patients with chronic kidney disease (CKD). However, it remains uncertain whether adequate cell functionality is maintained under uremic conditions. As chronic inflammation and oxidative stress in CKD may lead to the accumulation of senescent cells, we investigated cellular senescence of CKD MSCs and determined the effects of metformin on CKD‐associated cellular senescence in bone marrow MSCs from sham‐operated and subtotal nephrectomized mice and further explored in adipose tissue‐derived MSCs from healthy kidney donors and patients with CKD. CKD MSCs showed reduced proliferation, accelerated senescence, and increased DNA damage as compared to control MSCs. These changes were significantly attenuated following metformin treatment. Lipopolysaccharide and transforming growth factor β1‐treated HK2 cells showed lower tubular expression of proinflammatory and fibrogenesis markers upon co‐culture with metformin‐treated CKD MSCs than with untreated CKD MSCs, suggestive of enhanced paracrine action of CKD MSCs mediated by metformin. In unilateral ureteral obstruction kidneys, metformin‐treated CKD MSCs more effectively attenuated inflammation and fibrosis as compared to untreated CKD MSCs. Thus, metformin preconditioning may exhibit a therapeutic benefit by targeting accelerated senescence of CKD MSCs.

show abstract

Section: Introductionmentioning

confidence: 99%

Metformin inhibits chronic kidney disease‐induced DNA damage and senescence of mesenchymal stem cells

Kim

Yu²,

Lee

et al. 2021

Aging Cell

View full text Add to dashboard Cite

show abstract

“…The therapeutic methods so far were function-limited and if the treatment intervention was not timely, could deteriorate into chronic kidney disease, and many patients suffer from chronic pain for a long time [27] . Cell-based therapies and tissue regeneration are new approach to overcome the present limitations of kidney injury healing [28,29] . MSCs were a promising therapeutic tool in regenerative medicine due to their self-renewal and multidirectional differentiation potency.…”

Section: Discussionmentioning

confidence: 99%

Platelet-rich plasma enhanced MSCs repair for glycerin-induced acute kidney injury via AKT/Rab27 paracrine pathway

Zhang

Zhou

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Acute kidney injury (AKI) was defined by rapid deterioration of renal function, as a common complication in hospitalized patients. Among the recent therapeutic options, mesenchymal stem cells (MSCs) were considered a promising therapeutic strategy for damaged tissues repair. Platelet rich plasma (PRP) regulates stromal cells to repair tissue damage through the release of growth factors. Here we proposed a possible therapeutic use of human umbilical cord mesenchymal stem cells stimulated by platelet-rich plasma (PRP-MSCs) in glycerin-induced acute kidney injury murine model.Methods: In vivo, we constructed glycerin-induced acute kidney injury rat models. On day 1 post injury, rat received a tail vein injection of 1×106 MSCs and 1×106 PRP-MSCs. All animals were sacrificed at Day 3 after glycerin injection. In vitro, NRK-52E cells were damaged by 20% glycerol for 12 hours, after that NRK-52E incubated with MSCs and PRP-MSCs for 24 hours in transwell co-culture system, DMEM as a negative control. NRK-52E cells were harvested for apoptosis assay, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). Then the number of MSCs exosomes stimulated by PRP was detected by confocal microscopy and Nanosight tracking analysis (NTA), PRP-MSCs-Ex (10mg/kg) and MSCs-Ex (10mg/kg) were injected intravenously, saline as control. The therapeutic effect of PRP-MSCs was evaluated by analyzing renal function (serum BUN, Creatinine), histopathological structure changes and apoptosis and proliferation of renal tubular cells. Results: In vivo and vitro studies confirmed that the PRP induced YAP nucleus expression to promoting the proliferation and reinforces the stemness of MSCs, and PRP could promoted the paracrine secretion of exosomes by MSCs to repair AKI though AKT/Rab27 pathway.Conclusions: Our results revealed that PRP stimulated MSCs paracrine pathway could effectively alleviate glycerin-induced acute kidney injury. Therefore, RPP pretreatment may be a new method to improve the therapeutic effect of MSCs.

show abstract

Section: Discussionmentioning

confidence: 99%

Platelet-rich Plasma Enhanced MSCs Repair for Glycerin-induced Acute Kidney Injury via AKT/Rab27 Paracrine Pathway

Zhang

Shi

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Acute kidney injury (AKI) was defined by rapid deterioration of renal function, as a common complication in hospitalized patients. Among the recent therapeutic options, mesenchymal stem cells (MSCs) were considered a promising strategy for damaged tissues repair. Platelet rich plasma (PRP) regulates stromal cells to repair tissue damage through the release of growth factors. Here we proposed a possible therapeutic use of human umbilical cord mesenchymal stem cells stimulated by platelet-rich plasma (PRP-MSCs) in a murine model of acute renal injury generated by glycerin injection.Methods: In vivo, we constructed cisplatin-induced acute kidney injury rat models. On day 1 post injury, rat received a tail vein injection of 1×106 MSCs and 1×106 PRP-MSCs. All animals were sacrificed at Day 3 after glycerin injection. Renal function (serum BUN, Creatinine), histopathological structure changes and tubular cells apoptosis were evaluated. In vitro experiment, 50 μmol/L of glycerin treated NRK-52E for 12h were incubated with MSC or PRP-MSC for 24h in transwell co-culture system. Cells were harvested for apoptosis assay, immunofluorescence assay, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR).Results: In vivo and vitro studies confirmed that the PRP induced YAP nucleus expression to promoting the proliferation and reinforces the stemness of MSCs, and stimulated the paracrine exosomes of MSCs by activating AKT/Rab27 signaling pathway to inhibiting the apoptosis of renal tubular cells. Conclusions: Our results revealed a novel potential use of PRP-MSCs as therapeutic strategy for acute kidney injury, highlighting the presence and role of the reno-protective factor PRP-MSCs.

show abstract

Mesenchymal stromal cell–based therapies for acute kidney injury: progress in the last decade

Cited by 50 publications

References 105 publications

Metformin inhibits chronic kidney disease‐induced DNA damage and senescence of mesenchymal stem cells

Metformin inhibits chronic kidney disease‐induced DNA damage and senescence of mesenchymal stem cells

Platelet-rich plasma enhanced MSCs repair for glycerin-induced acute kidney injury via AKT/Rab27 paracrine pathway

Platelet-rich Plasma Enhanced MSCs Repair for Glycerin-induced Acute Kidney Injury via AKT/Rab27 Paracrine Pathway

Contact Info

Product

Resources

About