IL‐7 overexpression enhances therapeutic potential of rat bone marrow mesenchymal stem cells for diabetic wounds

Khalid, Ramla Sana; Khan, Irfan; Zaidi, Midhat Batool; Naeem, Nadia; Haneef, Kanwal; Qazi, Rida‐e‐Maria; Habib, Rakhshinda; Malick, Tuba Shakil; Ali, Anwar; Salim, Asmat

doi:10.1111/wrr.12706

Cited by 11 publications

(12 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some of our previous reports have demonstrated the effect of genetic and chemical modification royalsocietypublishing.org/journal/rsfs Interface Focus 12: 20220017 of MSCs on improved angiogenesis. This includes genetic modification of MSCs with IL-7 with enhanced angiogenesis and wound tissue regeneration [26], and chemical modification of MSCs using isorhamnetin with upregulation in the gene and protein expression of growth factors involved in angiogenesis [20]. Similarly, dinitrophenol has been shown to modulate gene expression levels of angiogenic and cell survival factors in bone marrow derived MSCs [27].…”

Section: Discussionmentioning

confidence: 99%

Potential of stem cell seeded three-dimensional scaffold for regeneration of full-thickness skin wounds

et al. 2022

Self Cite

View full text Add to dashboard Cite

Hypoxic wounds are tough to heal and are associated with chronicity, causing major healthcare burden. Available treatment options offer only limited success for accelerated and scarless healing. Traditional skin substitutes are widely used to improve wound healing, however, they lack proper vascularization. Mesenchymal stem cells (MSCs) offer improved wound healing; however, their poor retention, survival and adherence at the wound site negatively affect their therapeutic potential. The aim of this study is to enhance skin regeneration in a rat model of full-thickness dermal wound by transplanting genetically modified MSCs seeded on a three-dimensional collagen scaffold. Rat bone marrow MSCs were efficiently incorporated in the acellular collagen scaffold. Skin tissues with transplanted subcutaneous scaffolds were histologically analysed, while angiogenesis was assessed both at gene and protein levels. Our findings demonstrated that three-dimensional collagen scaffolds play a potential role in the survival and adherence of stem cells at the wound site, while modification of MSCs with jagged one gene provides a conducive environment for wound regeneration with improved proliferation, reduced inflammation and enhanced vasculogenesis. The results of this study represent an advanced targeted approach having the potential to be translated in clinical settings for targeted personalized therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Potential of stem cell seeded three-dimensional scaffold for regeneration of full-thickness skin wounds

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…A variety of exogenous target genes can be integrated into MSCs genomic DNA and expressed for a long period of time, which is why MSCs have been successfully used as an ideal target cell for the treatment of diseases such as hematological disorders, lung injury, and bone defects. In addition, transfected MSCs have been shown to improve the low survival rate of transplanted cells in diabetic wound sites (Khalid et al, 2019). Researchers have already transfected BM-MSCs with adenovirus-vectored VEGF genes, which significantly promoted the repair of diabetic foot wounds in rats (Cai et al, 2014).…”

Section: Gene Therapymentioning

confidence: 99%

“…Researchers have already transfected BM-MSCs with adenovirus-vectored VEGF genes, which significantly promoted the repair of diabetic foot wounds in rats (Cai et al, 2014). Compared with untransfected MSCs, IL-7-transfected BM-MSCs were able to enhance cell-cell connections in diabetic foot trauma as well as promote angiogenesis through induction of angiogenic genes (Khalid et al, 2019). Because of the ability to stably express target genes transduced into cells, exploring specific target genes to enhance the efficacy of MSCs in repairing diabetic foot injury offers a promising future for regenerative medicine.…”

Section: Gene Therapymentioning

confidence: 99%

Stem Cell-Based Therapy for Diabetic Foot Ulcers

Qiao

Wang

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Diabetic foot ulcer has become a worldwide clinical medical challenge as traditional treatments are not effective enough to reduce the amputation rate. Therefore, it is of great social significance to deeply study the pathogenesis and biological characteristics of the diabetic foot, explore new treatment strategies and promote their application. Stem cell-based therapy holds tremendous promise in the field of regenerative medicine, and its mechanisms include promoting angiogenesis, ameliorating neuroischemia and inflammation, and promoting collagen deposition. Studying the specific molecular mechanisms of stem cell therapy for diabetic foot has an important role and practical clinical significance in maximizing the repair properties of stem cells. In addition, effective application modalities are also crucial in order to improve the survival and viability of stem cells at the wound site. In this paper, we reviewed the specific molecular mechanisms of stem cell therapy for diabetic foot and the extended applications of stem cells in recent years, with the aim of contributing to the development of stem cell-based therapy in the repair of diabetic foot ulcers.

show abstract

“…However, IL-7 has also been shown to regulate autoimmune responses and rebuild and maintain immune tolerance by inducing differentiation and proliferation of Treg cells in mouse models of autoimmune diseases and patients with type 1 diabetes ( 18 , 19 ). In addition, IL-7 can participate in tissue repair by enhancing the fusion characteristics of rat bone marrow mesenchymal stem cells, promoting their proliferation, differentiation, and migration ability, and inducing the secretion of pro-regeneration factors ( 20 , 21 ).…”

Section: Introductionmentioning

confidence: 99%

IL-7-Treated Periodontal Ligament Cells Regulate Local Immune Homeostasis by Modulating Treg/Th17 Cell Polarization

Zhang

Huang

et al. 2022

Front. Med.

View full text Add to dashboard Cite

Both interleukin (IL)-7 and human periodontal ligament cells (hPDLCs) have immunomodulatory properties. However, their combined effect on CD4+T cells has never been studied. In this study, we aimed to investigate the effect of conditioned medium of hPDLCs treated with rhIL-7 on the differentiation of CD4+T cells into regulatory T cells/T helper 17 cells (Treg/Th17 cells) and observe the effect of IL-7 on the immunomodulatory properties of PDLCs. After hPDLCs were treated with different concentrations of rhIL-7 for 24 h, the collected supernatants were used to incubate CD4+T cells for 3 days. A gamma-secretase inhibitor (DAPT) was used to suppress the activation of the Notch1 signaling pathway. Cell proliferation, apoptosis, and necrosis were determined using the cell counting kit-8 (CCK-8) and flow cytometry (FCM). The expressions of forkhead box P3 (Foxp3) in CD4+T cells and transforming growth factor (TGF-β) and IL-6 in the supernatants were determined by ELISA. Reverse transcription-quantitative PCR (RT-qPCR), and the Western blot (WB) determined the mRNA levels and protein expression of various target factors. FCM was used to detect the mean fluorescence intensity of PD-L1 in hPDLCs and to analyze the differentiation of Treg/Th17 cells. Our results showed that IL-7 promoted proliferation and inhibited apoptosis in hPDLCs, promoted the expression of TGF-β, PD-L1, Notch1, Jagged1, and Hes1, and inhibited the levels of hypoxia-inducible factor (HIF)-1α and TCF7, whereas the addition of DAPT effectively reversed these effects. Importantly, we found that the conditioned medium of hPDLCs treated with rhIL-7 promoted the polarization of CD4+T cells into Treg cells but had no significant effect on the differentiation of Th17 cells. Our study indicated that treatment of PDLCs with IL-7 can promote the polarization of CD4+T cells into Treg cells by modulating the expression of inflammatory factors and signaling molecules through activating the Notch1 signaling pathway, thus participating in the regulation of immune homeostasis in the periodontal microenvironment.

show abstract

IL‐7 overexpression enhances therapeutic potential of rat bone marrow mesenchymal stem cells for diabetic wounds

Cited by 11 publications

References 47 publications

Potential of stem cell seeded three-dimensional scaffold for regeneration of full-thickness skin wounds

Potential of stem cell seeded three-dimensional scaffold for regeneration of full-thickness skin wounds

Stem Cell-Based Therapy for Diabetic Foot Ulcers

IL-7-Treated Periodontal Ligament Cells Regulate Local Immune Homeostasis by Modulating Treg/Th17 Cell Polarization

Contact Info

Product

Resources

About