Therapeutic Potential Of Stem Cells Research Articles

Therapeutic potential of stem cells in subarachnoid hemorrhage

Therapeutic potential of stem cells in subarachnoid hemorrhage

Effects of Ibuprofen and Diclofenac Pre-Treatment on Viability and Apoptosis Processes in Human Dental Pulp Stem Cells

Background and Objectives: Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, which is managed by using nonsteroidal anti-inflammatory drugs (NSAIDs). However, information is limited about how NSAIDs affect the therapeutic potential of stem cells. Materials and Methods: We investigated the effects of ibuprofen and diclofenac on the characteristics, morphology, and immunophenotype of human mesenchymal stromal cells isolated from the dental pulp (DPSCs) and cultured in vitro, as well as their effects on the expression of angiogenic growth factors (VEGFA and HGF) and selected genes in apoptosis signalling pathways (BAX, BAK, CASP3, CASP9, and BCL2). Results: Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of HGF, while the expression of VEGFA remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including the upregulation of CASP9 and BCL2, with decreased CASP3 expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. Conclusions: Our results suggest that concomitant use of the NSAIDs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, affecting the efficacy of stem cell therapy.

Aqueous two‐phase systems as a novel alternative in the primary recovery of human mesenchymal cells obtained from adipose tissue

AbstractIn recent years, therapies based on regenerative medicine have gained wide interest owing to their potential in organ transplantation and in the treatment of multiple diseases. These cell‐based therapies rely mainly on the therapeutic potential of stem cells as a result of their self‐renewal, differentiation, capacities and immunosuppressive properties. Adipose tissue contains a large number of mesenchymal stem cells compared to other tissues and is easily accessible through noninvasive techniques; hence the primary recovery of adipose‐derived mesenchymal stem cells (ASC) has become a critical step. Aqueous two‐phase systems (ATPS) have shown promise as a separation technique for mesenchymal stem cells (MSC) as a result of their scalability, cost‐effectiveness and compatibility. In this study, we investigated the partitioning behavior of the stromal vascular fraction cells, including ASC, in different ATPS compositions [polyethylene glycol, dextran (DEX), Ficoll and Ucon). Among the three ATPS tested, most of the ASC consistently migrates to the top phase as indicated by immunostaining studies for CD73, CD90 and CD105 stem cell markers. Nevertheless, the Ficoll–DEX system retrieves the greatest quantity of ASC recovered in the top phase (89% of total ASC), whereas the Ucon–DEX system effectively eliminates the most contaminating cells (38%). Our findings provide insights into the conditions under which ASC and contaminant cells concentrate in opposite phases in different ATPS, which can contribute to the development of efficient and scalable separation systems for MSC in regenerative medicine and tissue engineering applications. © 2024 Society of Chemical Industry (SCI).

An Updated Review on the Therapeutic Potential of Stem Cells for Treating Cardiovascular Disorders

Despite significant progress in the field of medicine, cardiovascular illnesses continue to be the primary cause of mortality on a global scale. The increasing prevalence of cardiovascular illnesses necessitates the exploration of novel and potential therapeutic strategies to address the escalating risk associated with CVDs. Stem cell therapy has emerged as the central focus of regenerative cardiovascular medicine, surpassing all other treatments and therapies. Multiple clinical trials and studies have demonstrated that stem cell therapy, particularly mesenchymal stem cells, is the most appealing approach for treating cardiac disorders due to their significant therapeutic potential. Recent research have shown that mesenchymal stem cells have a positive impact on several cardiac muscle diseases, such as heart failure, problems with blood vessel lining, damage caused by lack of blood flow, and high blood pressure in the lungs. This study specifically examines the potential, preconditioning techniques, methods of administration, and mechanisms of mesenchymal stem cell (MSC) therapy for the treatment of cardiovascular diseases (CVDs).

Stem Cell and Neural Progenitor Cell Therapy for Neurogenic Bladder—Where Are We in 2023?

Abstract Purpose of Review This review aims to consolidate the currently available literature regarding the treatment of neurogenic bladder (NGB) with stem cells or neural progenitor cells (NPCs). Recent Findings Several promising studies published in the past 5 years suggest therapeutic potential of stem cells in treating NGB. In vitro models of NGB have demonstrated the efficacy of stem cells from varying sources to induce nerve regeneration while simultaneously improving bladder function parameters. Additionally, mesenchymal stem cells (MSCs) were found to inhibit fibrosis through the TGF-β1 signaling pathway while their effects were potentiated by elevated levels of BDNF or SDF-1. Among induced pluripotent stem cells (iPSCs), it was noted that autophagy inducers improved regenerative effects. NPCs, in a recent clinical trial, also underscored the potential for translating stem cell therapies into practice. Summary Stem cells offer a potentially revolutionary regenerative medicine strategy for treatment of NGB. Many in vivo trials are promising, but there is a distinct shortage of clinical trials attempting to translate this success into human subjects. In the future, research should be directed towards understanding the complex mechanisms of stem cell-based therapy while moving towards the clinical applications of the technology.

Mesenchymal stem cell-derived extracellular vesicles for human diseases

Stem cell therapy is a novel approach for treating various severe and intractable diseases, including autoimmune disorders, organ transplants, tumors, and neurodegenerative diseases. Nevertheless, the extensive utilization of stem cells is constrained by potential tumorigenicity, challenges in precise differentiation, rejection concerns, and ethical considerations. Extracellular vesicles possess the ability to carry diverse bioactive factors from stem cells and deliver them to specific target cells or tissues. Moreover, they offer the advantage of low immunogenicity. Consequently, they have the potential to facilitate the therapeutic potential of stem cells, mitigating the risks associated with direct stem cell application. Therefore, the use of stem cell extracellular vesicles in clinical diseases has received increasing attention. This review summarizes advances in the use of extracellular vesicles from mesenchymal stem cells (MSC). MSC extracellular vesicles are used in the treatment of inflammatory diseases such as rheumatoid arthritis, liver injury, COVID-19, and allergies; in the repair of tissue damage in heart disease, kidney injury, and osteoarthritic diseases; as a carrier in the treatment of tumors; and as a regenerative agent in neurodegenerative disorders such as Alzheimer's and Parkinson's.

Therapeutic Potential of Stem Cells in Natural Killer-Like B Cell-Associated Diseases.

Stem cells are undifferentiated cells possessing a remarkable capacity to develop into multiple cell types. NKB cells, referred to "natural killer-like B cells," are recently identified subtype of B lymphocytes possessing characteristics that are similar to both natural killer (NK) cells and regular B lymphocytes. NK cells are lymphocyte-like in structure and cytotoxic in nature participating in the immediate immune response to the infected or malignant cells, whereas B lymphocytes produce antibodies and participate in adaptive immune response by binding to the specific antigen. The identification of NKB cells brings up new possibilities for studying and perhaps modulating immune responses in a variety of diseases, particularly those associated with microbial infections or inflammatory responses. Further, correlation of NKB cells with interleukins allows us to understand the molecular mechanism of diseases. Stem cell research offers a better understanding of NKB cell participation and provides new insights for novel treatment methods wherein mesenchymal stem cells (MSCs) have found to be the most promising stem cell showing positive outcomes in NKB cell-associated inflammatory diseases. Additionally, the perceptions acquired from researching NKB cells in diverse diseases leads to innovative treatment options, improving our capacity to control and cure immunological dysregulation-related ailments.

Therapeutic potential of stem cell and melatonin on the reduction of CCl4-induced liver fibrosis in experimental mice model

Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.

Advancing Spinal Cord Injury Treatment through Stem Cell Therapy: A Comprehensive Review of Cell Types, Challenges, and Emerging Technologies in Regenerative Medicine.

Spinal cord injuries (SCIs) can lead to significant neurological deficits and lifelong disability, with far-reaching physical, psychological, and economic consequences for affected individuals and their families. Current treatments for SCIs are limited in their ability to restore function, and there is a pressing need for innovative therapeutic approaches. Stem cell therapy has emerged as a promising strategy to promote the regeneration and repair of damaged neural tissue following SCIs. This review article comprehensively discusses the potential of different stem cell types, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and neural stem/progenitor cells (NSPCs), in SCI treatment. We provide an in-depth analysis of the unique advantages and challenges associated with each stem cell type, as well as the latest advancements in the field. Furthermore, we address the critical challenges faced in stem cell therapy for SCIs, including safety concerns, ethical considerations, standardization of protocols, optimization of transplantation parameters, and the development of effective outcome measures. We also discuss the integration of novel technologies such as gene editing, biomaterials, and tissue engineering to enhance the therapeutic potential of stem cells. The article concludes by emphasizing the importance of collaborative efforts among various stakeholders in the scientific community, including researchers, clinicians, bioengineers, industry partners, and patients, to overcome these challenges and realize the full potential of stem cell therapy for SCI patients. By fostering such collaborations and advancing our understanding of stem cell biology and regenerative medicine, we can pave the way for the development of groundbreaking therapies that improve the lives of those affected by SCIs.

Harnessing the Therapeutic Potential of Stem Cells in the Management of Chronic Obstructive Pulmonary Disease: A Comprehensive Review.

Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory condition with limited treatment options. Stem cell therapy has emerged as a promising approach for COPD management due to its regenerative and immunomodulatory properties. This review article aims to comprehensively explore the therapeutic potential of stem cells in COPD management. The introduction provides background on COPD, highlighting its impact on health and the need for novel therapies. The different types of stem cells relevant to COPD, including embryonic stem cells, adult stem cells, and induced pluripotent stem cells, are described along with their properties and characteristics. The pathogenesis of COPD is discussed, emphasizing the key mechanisms involved in disease development and progression. Subsequently, the role of stem cells in tissue repair, regeneration, and immunomodulation is examined, highlighting their ability to address specific pathological processes in COPD. Mechanisms of action, such as paracrine signaling, immunomodulation, anti-inflammatory effects, and tissue regeneration, are explored. The interaction between stem cells and the host environment, which promotes lung repair, is also discussed. Challenges in stem cell therapy for COPD, including optimal cell sources, delivery methods, safety, and efficacy, are identified. Regulatory considerations and the importance of standardization are emphasized. Potential strategies for optimizing the therapeutic potential of stem cells in COPD management, such as combination therapies and preconditioning techniques, are outlined. Emerging trends and future directions are highlighted, including advanced cell engineering and patient-specific induced pluripotent stem cells. In conclusion, stem cell therapy holds significant promise for COPD management, addressing the limitations of current treatments. Continued research and development are necessary to overcome challenges, optimize therapies, and realize stem cells' full potential in improving the lives of patients with COPD.

Bio-Inspired Nanocarriers Derived from Stem Cells and Their Extracellular Vesicles for Targeted Drug Delivery.

With their seemingly limitless capacity for self-improvement, stem cells have a wide range of potential uses in the medical field. Stem-cell-secreted extracellular vesicles (EVs), as paracrine components of stem cells, are natural nanoscale particles that transport a variety of biological molecules and facilitate cell-to-cell communication which have been also widely used for targeted drug delivery. These nanocarriers exhibit inherent advantages, such as strong cell or tissue targeting and low immunogenicity, which synthetic nanocarriers lack. However, despite the tremendous therapeutic potential of stem cells and EVs, their further clinical application is still limited by low yield and a lack of standardized isolation and purification protocols. In recent years, inspired by the concept of biomimetics, a new approach to biomimetic nanocarriers for drug delivery has been developed through combining nanotechnology and bioengineering. This article reviews the application of biomimetic nanocarriers derived from stem cells and their EVs in targeted drug delivery and discusses their advantages and challenges in order to stimulate future research.

Ameliorative potential of stem cells from human exfoliated deciduous teeth (SHED) in preclinical studies: A meta-analysis

The preclinical and clinical role of mesenchymal stem cells from various adult sources is extensively investigated and established in regenerative medicine. However, the comprehensive exploration of the therapeutic potential of Stem cells from human exfoliated deciduous teeth (SHED) is inadequate. Therefore, we performed a systematic meta-analysis of preclinical animal model studies in several diseases to provide insight into SHED's efficacy and therapeutic potential. Two blinded and independent investigators searched the available online databases and scrutinized the included studies. Meta-analysis was performed to evaluate the pooled effect estimate of intervention of SHED by Review Manager 5.4.1. To investigate the therapeutic efficacy of SHED intervention, we also analyzed the test of heterogeneity (I2), overall effect (Z), sensitivity, and publication bias. Among the 2156 scrutinized studies, 40 were included and evaluated as per inclusion and exclusion criteria. The intervention of SHED and its derivatives in several diseases depicted statistically significant therapeutic effects in periodontitis, pulpitis, spinal cord injury, parkinson's disease, alzheimer's disease, focal cerebral ischemia, peripheral nerve injury, and retinal pigmentosa. SHED also improved levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin in liver fibrosis . In autoimmune diseases also, values were significant. SHED also showed a statistically significant reduction of wound healing area and new bone formation in bone defects. The pooled effect estimates of included preclinical studies demonstrated a statistically significant therapeutic effect of SHED in numerous diseases. Based on our data, it is suggested that the potential of SHED may be implemented in clinical trials after conducting a few more preclinical studies.

Therapeutic potential of stem cells and acitretin on inflammatory signaling pathway-associated genes regulated by miRNAs 146a and 155 in AD-like rats

Alzheimer’s disease (AD) is one of the most common causes of dementia. Several drugs are used to improve the symptoms, but do not stop AD progression. There are more promising treatments that may have a significant role in AD diagnosis and treatment such as miRNAs and stem cells. The present study aims to develop a new approach for AD treatment by mesenchymal stem cells (MSCs) and/or acitretin with special reference to inflammatory signaling pathway as NF-kB and its regulator miRNAs in AD-like rat model. Fourty-five male albino rats were allotted for the present study. The experimental periods were divided into induction, withdrawal, and therapeutic phases. Expression levels of miR-146a, miR-155, necrotic, growth and inflammatory genes were assessed using RT-qPCR. Histopathological examination of brain tissues was performed in different rat groups. The normal physiological, molecular, and histopathological levels were restored after treatment with MSCs and/or acitretin. The present study demonstrates that the miR-146a and miR-155 might be used as promising biomarkers for AD. MSCs and/or acitretin proved their therapeutic potential in restoring the expression levels of targeted miRNAs and their related genes concerning NF-kB signaling pathway.

Cultivation and cryopreservation of rat stem cells and their interaction with lyophilised acellular matrix

With the rapid development of regenerative medicine in the 21st century, the study of the therapeutic potential of stem cells in both preclinical research and clinical trials has become particularly relevant. Preclinical studies on animals allow for a detailed understanding of the mechanisms of action of allogzeneic cell preparations, exploring their regenerative activity, pharmacodynamics, and potential side effects. The purpose of the study was to select optimal conditions for obtaining, cultivating, and cryopreserving mesenchymal stem cells from rats and analyse their interaction with the lyophilised acellular matrix. The enzymatic method was applied to obtain primary cell cultures from the umbilical cord, dermis, and muscles of Rattus norvegicus fetuses. Cell cultures were cultivated in vitro, and cell line proliferation rates were analysed using an inverted microscope. In addition, cryopreservation was performed to store cellular materials. The interaction of mesenchymal stem cells with an acellular matrix and cryopreservation of the obtained cells was at the 4 and 5th passages. It was shown that the optimal nutrient medium for cultivating the obtained lines of mesenchymal stem cells from the umbilical cord and dermis of rat fetuses is DMEM/F12 Advanced. It was established that the method of thawing the cell suspension by 10-fold dilution of dimethyl sulfoxide is more effective than the alternative method of immediate removal of cryoprotectant by centrifugation. The lyophilised acellular dermal matrix was found to have a cytotoxic effect on all cultured rat cells, while the pericardial matrix showed a positive effect on the growth of the investigated cell lines. Thus, the optimal nutrient medium and conditions for freezing/thawing of rat stem cells were selected, and the effect of lyophilised acellular matrix, planned for therapeutic use, on the obtained cell lines was determined

Controlling the Stem Cell Environment Via Conducting Polymer Hydrogels to Enhance Therapeutic Potential

AbstractStem cells are a promising treatment option for various neurological diseases such as stroke, spinal cord injury, and other neurodegenerative disorders. However, the ideal environment to optimize the therapeutic potential of the cells remains poorly understood. Stem cells in the native environment are influenced by a combination of mechanical, chemical, and electrical cues for proliferation and differentiation. Because of their controllable properties, conductive hydrogels are promising biomaterials to interact with stem cells. Herein, this work develops an interpenetrating conducting polymer hydrogel with tunable mechanical properties. The hydrogel serves as a platform to provide mechanical and electrical cues for interactions with mesenchymal stem cells (MSCs). This work optimizes the formulation of the hydrogel for maximum viability of MSCs and relatively higher cytoskeletal protein expression. The viability of cells is not affected due to electrical stimulation (ES). Further, ES alters the trophic factor secretion of MSCs, with significant increase in VEGF pathway genes—VEGFA and HSPB1. In addition, substrate stiffness of the hydrogel enhances the VEGFB secretion compared to control. Hence, the conducting polymer hydrogel system creates a tunable physical and electrical niche to enhance the therapeutic potential of stem cells for neurological injuries.

Combinatorial Therapeutic Potential of Stem Cells and Benzimidazol Derivatives for the Reduction of Liver Fibrosis.

(1) Background: Liver fibrosis is currently one of the top ten causes of death worldwide. Stem cells transplantation using mesenchymal stem cells (MSCs) is an alternative therapy which is used in the place of organ transplant, due to the incapacity of stem cells to endure oxidative stress in the damage site, thus affecting the healing process. The present study aimed to enhance the therapeutic potential of MSCs using combined therapy, along with the novel synthetic compounds of benzimidazol derivatives. (2) Methods: Eighteen compound series (benzimidazol derivatives) were screened against liver fibrosis using an in vitro CCl4-induced injury model on cultured hepatocytes. IC50 values were calculated on the bases of LDH assay and cell viability assay. (3) Results: Among the eighteen compounds, compounds (10), (14) and (18) were selected on the basis of IC50 value, and compound (10) was the most potent and had the lowest IC50 value in the LDH assay (8.399 ± 0.23 uM) and cell viability assay (4.73 ± 0.37 uM). Next, these compounds were combined with MSCs using an in vitro hepatocytes injury culture and in vivo rat fibrotic model. The effect of the MSCs + compounds treatment on injured hepatocytes was evaluated using LDH assay, cell viability assay, GSH assay and real-time PCR analysis and immuno-staining for caspase-3. Significant reductions in LDH level, caspase-3 and apoptotic marker genes were noted in MSCs + compounds-treated injured hepatocytes. In vivo data also showed the increased homing of the MSCs, along with compounds after transplantation. Real-time PCR analysis and TUNEL assay results also support our study. (4) Conclusions: It was concluded that compounds (10), (14) and (18) can be used in combination with MSCs to reduce liver fibrosis.

Exploring the therapeutic potential of stem cells in glaucoma: A promising frontier for vision restoration

Exploring the therapeutic potential of stem cells in glaucoma: A promising frontier for vision restoration

Induction of Targeted Differentiation of Dermal Mesenchymal Stem Cells Into Neural Lineage According to Peroxiredoxin II Expression.

To optimize the therapeutic potential of stem cells in stem cell therapy for neurological diseases, it is crucial to enhance the differentiation, migration, and neural network formation of stem cells, and to eliminate uncertain cell differentiation and proliferation factors. Several studies have shown that reactive oxygen species (ROS) are important factors in the regulation of neurogenesis, and Prx II (Peroxiredoxin II) is a gene that regulates ROS. As the entry point in this study to conduct a bioinformatics analysis of the sequencing results of Prx II+/+ dermal mesenchymal stem cells (DMSCs) and Prx II-/- DMSCs. lncRNA/miRNA/mRNA networks were then constructed and preliminarily verified in RT-qPCR experiments. In this study, a total of 11 hub genes (Gria1, Nrcam, Sox10, Snap25, Cntn2, Dlg2, Ngf, Ntrk3, Amph, Syt1, and Cd24a), eight miRNAs (miRNA-4661, miRNA-34a, miRNA-185, miRNA-34b-5p, miRNA-34c, miRNA-449a, miRNA-449b, miRNA-449c) and 12 lncRNAs (Dubr, Gas5, Gm20427, Gm26917, Gm42547, Gm8066, Kcnq1ot1, Malat1, Mir17hg, Neat1, Rian, and Tug1) were predicted in lncRNA/miRNA/mRNA network. The regulatory mechanism of Prx II in the differentiation of DMSCs into neurons through ROS was explored, and a theoretical basis was determined that can be applied in future research on nervous system diseases and the clinical applications of stem cells.

Stem Cell Therapies for Gastrointestinal Anastomotic Healing: A Systematic Review and Meta-Analysis on Results from Animal Studies

Background: Despite considerable progress in surgical techniques, anastomotic leak (AL) is a common complication after gastrointestinal surgery. Stem cells are a promising therapy to improve healing and have been used in gastrointestinal anastomoses. In this study, we perform a systematic review and meta-analysis to evaluate the efficacy of stem cell therapies in preventing ALs among animal studies. Methods: A systematic review of the literature was performed by searching PubMed, Web of Science, and the Cochrane Library. We considered all anastomoses of the gastrointestinal tract (excl. biliary) from the esophagus to the rectum. Outcomes included AL rates on postoperative day (POD) 7 and the latest time point reported. Results: Fourteen studies were identified, evaluating stem cells in gastrointestinal anastomoses, of which 1 was on esophageal, 2 on gastric, 2 on small intestinal, and 9 on colorectal anastomoses. Meta-analysis did not show significant differences in AL rates on POD 7 (odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.04–3.15, p = 0.248, I2 = 34.1%, 95% CI: 0–75.2%, Q = 6.07, df = 4, p = 0.194), but there was a nonsignificant trend for lower AL rates at the latest time point reported (OR 0.28, 95% CI: 0.08–1.01, p = 0.052, I2 = 34%, 95% CI: 0–70.8%, Q = 10.6, df = 7, p = 0.157). Conclusion: Stem cell therapy may be associated with lower AL rates in gastrointestinal anastomoses, though meta-analysis is severely inhibited by heterogeneous study design. More studies are needed to determine the therapeutic potential of stem cells.

404.7: Study on the Regulatory Effect of iPS-Derived Exosomes on the Local Immune Microenvironment in DCD Kidney Transplanted Rats

Introduction: Ischemia reperfusion injury (IRI) of donation After Cardiac death (DCD) transplanted kidney is the key factor of acute renal injury, acute and chronic rejection of renal transplantation and transplanted kidney disease.The latest researches show that mesenchymal stem cells (MSCs) have the function of protecting damaged tissues and organs and strong immune regulation. Induced pluripotent stem (iPS) cells have higher proliferative capacity and exosome secretion potential than MSCs. In addition to the functions of stem cells, exosomes have the unique ability to cross the blood-brain barrier and deliver remotely, which means that exosomes have better advantages in clinical disease treatment compared with the therapeutic potential of stem cells. Therefore, the main purpose of this study is to clarify the role of IPS derived exosomes in protecting the IRI of DCD transplanted kidney and regulating its local immune microenvironment. Methods: The iPS cells were passaged to the third passage and massively expanded. After 48 hours of culture, 100 mL of cell culture supernatant was collected and exosomes were extracted from the supernatant by the kit method, and the morphology and surface membrane marker proteins of the exosomes were identified. The SD rats were established with DCD renal transplantation model and 10, 50, and 100 μg of exosomes were infused into that SD rats respectively, and a PBS control group was set at the same time. On the 3rd, 5th, 7th, 14th and 28th days after transplantation, the content of cytokines in the serum of the recipient rats, the proportion of lymphocyte subsets CD4+CD25+Foxp3+Tregs in the spleen and the relative expression of Foxp3 mRNA were detected. The proliferation of renal tubular cells was detected by PCNA immunofluorescence. The pathological changes of renal tissue were determined by HE staining, and the apoptosis of renal tubular epithelial cells was detected by Tunel staining. The infiltration of inflammatory cells was detected by immunohistochemistry. The expression changes of regulatory T cells in renal tissue and macrophage phenotypic characteristics were analyzed by flow cytometry. Results: The experimental amount of exosomes was successfully obtained, and the morphology was observed by transmission electron microscope. The exosomes were round or oval membranous vesicles with uniform size, and the edges were clearly visible. The TSG101, CD63, and CD9 proteins were highly expressed on the exosome membrane surface by western-blot. A DCD rat kidney transplantation model was successfully established. The expression levels of IL-12, IL-2, IFN-γ, and TNF-α in the serum of each group were increased to varying degrees from the 3rd day after operation. On the 3rd and 7th days, the levels of IL-12, IL-2, IFN-γ, and TNF-α in the 100 μg exosome infusion group were significantly lower than those in the 10 μg, 50 μg and PBS groups (P<0.05), and the expression level of IL-10 in the 100 μg exosome infusion group was significantly higher than 10μg, 50μg and PBS groups (P<0.05). On the 28th day, the expression level of IL-10 in the 100 μg exosome infusion group was significantly higher than other groups (P<0.01). Compared with other groups, the CD4+CD25+Tregs and CD4+CD25+Foxp3+Tregs accounted for the highest proportion of CD4+T cells in the spleen of the 100μg infusion group (P<0.05). On the 28th day, the expression level of Foxp3 mRNA in the 100 μg infusion group was significantly higher than that in the 50 μg group (P<0.05). The stainings of PCNA, HE and Tunel showed that SD rats infused with 100μg exosomes could significantly reduce the pathological damage, inflammatory response and apoptosis of renal tubular epithelial cells in the transplanted kidney, promote the proliferation of renal tubular epithelial cells, and have a protective effect on IRI kidney. On the 28th day, the expression of CD4+CD25+Foxp3+Tregs cells in the transplanted kidney tissue was significantly increased, which further promoted the differentiation of macrophages into the immunomodulatory M2 subset. Conclusions: The infusion of iPS-derived high-dose exosomes is involved in the protection of the DCD kidney transplant during IRI process, and alleviates the acute and chronic injury of the DCD kidney transplant, and promotes the formation of the local immunosuppressive microenvironment in the DCD kidney transplantation. The National Natural Science Foundation of China (No.81900686).