Mesenchymal Stem Cells Loaded with Gelatin Microcryogels Attenuate Renal Fibrosis

Abstract

Background The treatment of chronic kidney diseases (CKDs) by different approaches using mesenchymal stem cells (MSCs) has made great strides. In this study, we aimed to explore the potential mechanism of gelatin microcryogels (GMs) as a cell therapeutic vector to block the progression of CKD. Methods In vivo, the pedicled omentum valve with MSC-loaded GMs was packed onto 5/6 nephrectomized kidneys derived from rats. The therapeutic effects were evaluated. In vitro, TNF-α, TGF-β, and MSCs were added to the medium of the HK-2 cell culture system, and key genes involved in anti-inflammatory and antifibrosis effects were evaluated by qPCR. Results After 12 weeks of MSC transplantation, kidney functions, such as serum creatinine, urea nitrogen, and 24-hour urine protein, were significantly improved. The pedicled omentum valve was packed with MSC-loaded GMs onto the 5/6 nephrectomized kidney, and the expressions of collagen IV, α-SMA, and TGF-β were all evaluated by immunohistochemical staining and western blot analysis. MSC-loaded-GMs also showed antifibrotic effects by inducing the upregulation of HO-1, BMP-7, and HGF and the downregulation of MCP-1 at the mRNA level. Four weeks after MSC-loaded GM treatment, we found that the mRNA levels of TNF-α and IL-6 were clearly reduced. MSC-conditional medium (MSC-CM) showed that the TNF-α-induced expression of IL-8 and IL-6 mRNA was reversed; E-cadherin mRNA was upregulated; and the TGF-β-induced expression of collagen IV, α-SMA, and fibronectin (FN) mRNA in HK-2 cells was reduced. Conclusions We demonstrated that the pedicled omentum valve packed with MSC-loaded GMs had a renal protective effect on the 5/6 nephrectomized kidney by observing the anti-inflammatory and antifibrosis effects.

Ultrasound enhances the therapeutic potential of mesenchymal stem cells wrapped in greater omentum for aristolochic acid nephropathy

“…Compared with the AAN-saline group, the expression of the inflammatory factors TNF-alpha, IL-1β, and IL-6 decreased in the AAN-MSC group, indicating that MSCs showed anti-inflammatory activity. These results are consistent with our previous study showing that the application of pedicled greater omentum flaps loaded with MSC-loaded gelatine microcryogels for the treatment of 5/6 nephrectomized kidneys significantly improved the function of the residual kidney via anti-fibrotic and anti-inflammatory mechanisms [ 19 ]. When the expression of TNF-α, a proinflammatory cytokine, was downregulated, CD206 expression in the AAN-MSC group was increased compared with that in the AAN-saline group.…”

“…Garcia-Gomez et al confirmed the ability of this unique omentum-mediated therapy to slow 5/6 nephrectomy-induced CKD [ 18 ]. Our previous research also confirmed that the pedicled omentum valve exerts a renoprotective effect on the kidney after 5/6 nephrectomy via anti-inflammatory and antifibrotic effects [ 19 ]. However, even if the omentum is used to prolong the survival of MSCs, their therapeutic efficacy may not be sufficient because MSCs cannot survive in the body for long periods.…”

“…Various approaches have been developed to improve the efficacy of MSC-based therapeutics for CKD after AKI, including an incubation with cytokines or chemical compounds [ 27 – 30 ] and the application of supporting materials [ 19 ]. At the same time, different injection methods, including intravenous or arterial injection, might also affect the efficacy of MSCs.…”

Urine-derived stem/progenitor cells: A focus on their characterization and potential

“…Many studies demonstrated the role and benefits of adult stem cells in kidney repair and regeneration, especially regarding MSCs[ 61 ]. Indeed, MSCs have shown to be efficient to reduce renal lesions in many models including rodent models of AKI induced by cisplatin[ 62 ], gentamicin[ 63 , 64 ] and ischemia reperfusion[ 65 - 67 ] and also in chronic kidney disease models[ 68 , 69 ].…”

Hydrogel Encapsulation: Taking the Therapy of Mesenchymal Stem Cells and Their Derived Secretome to the Next Level

“…In addition to immune regulation, antifibrosis is also an important function of MSCs. Gelatinmicrocryogel-loaded MSCs protected 5/6 nephrectomized kidneys through anti-inflammatory and anti-fibrotic effects (Geng et al, 2019). In a radiation therapy-induced esophageal fibrosis model, Kim et al used catechol-functionalized hyaluronic acid hydrogel-encapsulated MSC spheroids to improve esophageal injury (Kim et al, 2021).…”