Adipocytes Promote Endometrial Cancer Progression Through Activation of the SIRT1-HMMR Signaling Axis.

Adipocyte is a predominant component of the omental adipose tissue that influences the tumor microenvironment and increases the risk of endometrial cancer progression (EC), however, little is known about the underlying mechanism. In this study, using a co-culture model, we found that the adipocyte-EC cell interaction promoted SIRT1 signaling in vitro and in vivo xenograft mice models. Furthermore, immunostaining of SIRT1 protein showed significantly higher expression of SIRT1 in endometrial cancer patients than in normal endometria. RNA sequencing analysis revealed HMMR (hyaluronan-mediated motility receptor), an oncogene, as a downstream effector of SIRT1 in adipocyte-associated EC. Transient knockdown and chromatin immunoprecipitation assays showed that SIRT1 inhibition impedes transcription of the HMMR gene via FOXM1, and reduced expression of HMMR in co-cultured EC cells blocks AURKA activation via TPX2, leading to cell cycle arrest. This is the first study to report the positive correlation between SIRT1 and HMMR in EC patient tumors and might be used as a potential biomarker in EC. Notably, SIRT1 regulates HMMR expression in a FOXM1-dependent manner, and interfering with SIRT1 may provide a promising strategy for the management of endometrial cancer.

Chronic dietary iron overload affects hepatic iron metabolism and cognitive behavior in Wistar rats.

BACKGROUND: Iron accumulation in organs affects iron metabolism, leading to deleterious effects on the body. Previously, it was studied that high dietary iron in various forms and concentrations influences iron metabolism, resulting in iron accumulation in the liver and spleen and cognitive impairment. However, the actual mechanism and impact of long-term exposure to high dietary iron remain unknown. As a result, we postulated that iron overload caused by chronic exposure to excessive dietary iron supplementation would play a role in iron dyshomeostasis and inflammation in the liver and brain of Wistar rats. METHODS: Animals were segregated into control, low iron (FAC-Ferric Ammonium Citrate 5000 ppm), and high iron dose group (FAC 20,000 ppm). The outcome of dietary iron overload on Wistar rats was evaluated in terms of body weight, biochemical markers, histological examination of liver and brain tissue, and cognitive-behavioral studies. Also, gene expression of rat brain tissue involving iron transporters Dmt1, TfR1, iron storage protein Fpn1, inflammatory markers Nf-kB, Tnf-α, Il-6, and hepcidin was performed. RESULTS: Our data indicate that excess iron supplementation for 30 weeks leads to decreased body weight, increased serum iron levels, and decreased RBC levels in iron fed Wistar rats. Morris water maze (MWM) studies after 30 weeks showed increased escape latency in the high iron dose group compared with the control group. Histological studies of the high iron dose group showed an iron accumulation in the liver and brain loss of cellular architecture, and cellular degeneration was observed. Excess iron treatment showed upregulation of the Dmt1 gene in iron metabolism and a remarkable increase in the Nf-kB gene in rat brain tissue. CONCLUSION: The results show chronic excess iron supplementation leads to iron accumulation in the liver, leading to inflammation in Wistar rats.

Challenges and Outcomes of the First Stem Cell Transplant Program in Tanzania, East Africa.

Introduction: Due to the significant resources involved in creating HSCT programs there is a significant disparity in the availability of this treatment modality between the developed and developing countries. This manuscript details the process and the outcomes of the first HSCT program in East Africa which was started at Muhimbili National Hospital (MNH) in Dar-es-Salaam, Tanzania. Materials and Methods: Information and data were collected on the processes which had been implemented for starting the HSCT program at MNH. The details of the collaborations, training, infrastructure development, and acquisition of the biomedical equipment, as well as the actual process for HSCT, as well as the outcomes of treatment are described. Observations. The project has been detailed in 4 stages for ease of description: Stage 1: Preparatory work which was performed by the Government of Tanzania, as well as the administrators and clinicians from MNH (July 2017-September 2021). Stage 2: Exploratory gap analysis by the teams from MNH and International Haematology Consortium of HCG Hospital, India (HCG-IHC) in October 2021. Stage 3: Activities for closure of gaps (November 2021). Stage 4: Stem Cell Transplantation Camps (November 2021 to March 2022). 11 peripheral blood stem cell transplants were done in two camps, November 2021 (5 patients), and February 2022 (6 patients). 10 patients underwent autologous peripheral blood stem cell transplantation for multiple myeloma and 1 for lymphoma. The median duration of hospital stay was 19 ± 6 days. The median time for neutrophil engraftment, it was on 8.8 ± 0.8 days, and for platelet engraftment was 9.6 ± 2.4 days. Progression-free survival was 100%, and there was no mortality. Conclusion: Commonalities in the socioeconomic challenges in developing countries can be leveraged to create robust HSCT programs in other developing countries.

Whole transcriptome sequencing reveals HOXD11-AGAP3, a novel fusion transcript in the Indian acute leukemia cohort.

Introduction: Acute leukemia is a heterogeneous disease with distinct genotypes and complex karyotypes leading to abnormal proliferation of hematopoietic cells. According to GLOBOCAN reports, Asia accounts for 48.6% of leukemia cases, and India reports ~10.2% of all leukemia cases worldwide. Previous studies have shown that the genetic landscape of AML in India is significantly different from that in the western population by WES. Methods: We have sequenced and analyzed 9 acute myeloid leukemia (AML) transcriptome samples in the present study. We performed fusion detection in all the samples and categorized the patients based on cytogenetic abnormalities, followed by a differential expression analysis and WGCNA analysis. Finally, Immune profiles were obtained using CIBERSORTx. Results: We found a novel fusion HOXD11-AGAP3 in 3 patients, BCR-ABL1 in 4, and KMT2A-MLLT3 in one patient. Categorizing the patients based on their cytogenetic abnormalities and performing a differential expression analysis, followed by WGCNA analysis, we observed that in the HOXD11-AGAP3 group, correlated co-expression modules were enriched with genes from pathways like Neutrophil degranulation, Innate Immune system, ECM degradation, and GTP hydrolysis. Additionally, we obtained HOXD11-AGAP3-specific overexpression of chemokines CCL28 and DOCK2. Immune profiling using CIBRSORTx revealed differences in the immune profiles across all the samples. We also observed HOXD11-AGAP3-specific elevated expression of lincRNA HOTAIRM1 and its interacting partner HOXA2. Discussion: The findings highlight population-specific HOXD11-AGAP3, a novel cytogenetic abnormality in AML. The fusion led to alterations in immune system represented by CCL28 and DOCK2 over-expression. Interestingly, in AML, CCL28 is known prognostic marker. Additionally, non-coding signatures (HOTAIRM1) were observed specific to the HOXD11-AGAP3 fusion transcript which are known to be implicated in AML.

Biochemical separation of Cetuximab-Fab from papain-digested antibody fragments and radiolabeling with 64Cu for potential use in radioimmunotheranostics.

Engineered Fab fragments of monoclonal antibodies (mAbs) after radiolabeling with suitable radiometals have the potential to play a key role in personalized radioimmunotheranostics of cancer patients. In this study, we have generated Fab fragment of Cetuximab, a mAb targeting epidermal growth factor receptor (EGFR) expression and purified from the Fc and other fragments by ultrafiltration and affinity chromatography. The Cetuximab-Fab was conjugated with a suitable bifunctional chelator and radiolabeled with no-carrier-added (NCA) 64Cu produced via 64Zn (n, p) 64Cu reaction in a nuclear reactor. The radioimmunoconjugate obtained after size exclusion chromatographic separation possessed >95% radiochemical purity and it retained its integrity over at least three half-lives of the radiometal. Biodistribution studies was performed in fibrosarcoma tumor bearing Swiss mice, which demonstrated the explicit need for purification of the Cetuximab-Fab from Fc fragments. Enhanced and rapid tumor uptake with decent tumor-to-background ratio with prolonged retention was observed when radiolabeled purified Cetuximab-Fab was intravenously administered in animal models. Overall, this preclinical study established the pivotal role of separation science and technology to obtain the radioimmunoconjugate with requisite purity in order to demonstrate optimal pharmacokinetics and maximized treatment efficacy.

Amyloid fibril-based thixotropic hydrogels for modeling of tumor spheroids in vitro.

Biomaterials mimicking extracellular matrices (ECM) for three-dimensional (3D) cultures have gained immense interest in tumor modeling and in vitro organ development. Here, we introduce a new class of amyloid fibril-based peptide hydrogels as a versatile biomimetic ECM scaffold for 3D cell culture and homogenous tumor spheroid modeling. We show that these amyloid fibril-based hydrogels are thixotropic and allow cancer cell adhesion, proliferation, and migration. All seven designed hydrogels support 3D cell culture with five different cancer cell lines forming spheroid with necrotic core and upregulation of the cancer biomarkers. We further developed the homogenous, single spheroid using the drop cast method and the data suggest that all hydrogels support the tumor spheroid formation but with different necrotic core diameters. The detailed gene expression analysis of MCF7 spheroid by microarray suggested the involvement of pro-oncogenes and significant regulatory pathways responsible for tumor spheroid formation. Further, using breast tumor tissue from a mouse xenograft model, we show that selected amyloid hydrogels support the formation of tumor spheroids with a well-defined necrotic core, cancer-associated gene expression, higher drug resistance, and tumor heterogeneity reminiscent of the original tumor. Altogether, we have developed an easy-to-use, rapid, cost-effective, and scalable platform for generating in vitro cancer models for the screening of anti-cancer therapeutics and developing personalized medicine.

Targeted silencing of the MCL-1 gene using multi-layered dendrimer-based nanoconstructs achieves efficient tumor regression in xenografted mice models.

The setback in the practical clinical use of RNA interference (RNAi)-based cancer treatment stems from the lack of targeted small interfering RNA (siRNA) delivery. Here, we show that luteinizing hormone-releasing hormone(LHRH) analog-tethered multi-layered polyamidoamine (PAMAM) nanoconstructs silence the anti-apoptotic MCL-1 gene in LHRH receptor overexpressing human breast (MCF-7) and prostate cancer (LNCaP) cells with 70.91 % and 74.10 % efficiency, respectively. These results were confirmed by RT-PCR. The Acridine orange/Ethidium bromide (AO/EB) dual staining revealed that the silencing of MCL-1 induced apoptosis in both the cell lines. In vivo tumor regression studies performed using MCF-7 and LNCaP xenografted severe combined immunodeficiency(SCID) mice demonstrated highly improved tumor regression in groups treated with targeted nanoconstructs complexed with MCL-1 siRNA (T + siMCL-1) compared to the other treatment groups. The quantitative RT-PCR results of tumor tissues demonstrated significant MCL-1 gene silencing, i.e., 73.76 % and 92.63 % in breast and prostate tumors, respectively, after T + siMCL-1 treatment. Reduction in MCL-1 protein expression as assessed by immunohistochemistry further confirmed these results. Furthermore, the caspase 3/7 assay demonstrated apoptosis in the MCL-1 silenced tissues. The study strongly suggests that targeted delivery of siRNAs using multi-layered dendrimer nanostructures could be an effective therapy for LHRH overexpressing cancers.

Hyperthermia and doxorubicin release by Fol-LSMO nanoparticles induce apoptosis and autophagy in breast cancer cells.

Background: Studies on the anticancer effects of lanthanum strontium manganese oxide (LSMO) nanoparticles (NPs)-mediated hyperthermia at cellular and molecular levels are scarce. Materials & methods: LSMO NPs conjugated with folic acid (Fol-LSMO NPs) were synthesized, followed by doxorubicin-loading (DoxFol-LSMO NPs), and their effects on breast cancer cells were investigated. Results: Hyperthermia (45°C) and combination treatments exhibited the highest (∼95%) anticancer activity with increased oxidative stress. The involvement of intrinsic mitochondria-mediated apoptotic pathway and induction of autophagy was noted. Cellular and molecular evidence confirmed the crosstalk between apoptosis and autophagy, involving Beclin1, Bcl2 and Caspase-3 genes with free reactive oxygen species presence. Conclusion: The study confirmed hyperthermia and doxorubicin release by Fol-LSMO NPs induces apoptosis and autophagy in breast cancer cells.

Retrospective analysis of 34 febrile neutropenia episodes - therapeutic implication of multiplex polymerase chain reaction in infection diagnosis.

BACKGROUND: Hemato-oncologic patients on chemotherapy or undergoing bone marrow transplantation are susceptible to infections due to neutropenia. Incidences of febrile neutropenia (FN) in these patients are common, contributing to high mortality and morbidity. Lack of diagnosis of pathogens responsible for infections in these patients is a major healthcare challenge. Newer molecular diagnostics are increasingly becoming relevant. The objective of this retrospective study was to evaluate the effectiveness of Syndrome Evaluation System (SES), a multiplex molecular diagnostic platform for diagnosis of pathogens, and its impact on the management of FN. METHODS: In total, 34 neutropenic episodes from 21 patients admitted during September 2013 to April 2015 were analyzed in this study. Clinical samples from patients were tested on SES and routine culture. Treatment was as per standard of care. RESULTS: SES showed a 5-fold higher clinical sensitivity (55.9%) as compared to automated culture (11.1%). SES results were available within 14 hours as compared to >72 hours for culture, and elucidated change in antimicrobial therapy in 50% of episodes. Mortality rates were lower when SES was used early in the episode. De-escalation of antimicrobials according to SES results was possible, which translated into substantial cost saving. CONCLUSION: Newer non-culture-based molecular technologies like SES are changing the way we manage FN. It is faster, has a higher diagnostic yield as compared to traditional culture, and helps in making rapid, evidence-based therapeutic decision-making including de-escalation of antimicrobials. It would potentially lead to a reduction in mortality and healthcare cost in the long run.

Direct evidence of cellular transformation by prion-like p53 amyloid infection.

Tumor suppressor p53 mutations are associated with more than 50% of cancers. Aggregation and amyloid formation of p53 is also implicated in cancer pathogenesis, but direct evidence for aggregated p53 amyloids acting as an oncogene is lacking. Here, we conclusively demonstrate that wild-type p53 amyloid formation imparts oncogenic properties to non-cancerous cells. p53 amyloid aggregates were transferred through cell generations, contributing to enhanced survival, apoptotic resistance with increased proliferation and migration. The tumorigenic potential of p53 amyloid-transformed cells was further confirmed in mouse xenografts, wherein the tumors showed p53 amyloids. p53 disaggregation rescued the cellular transformation and inhibited tumor development in mice. We propose that wild-type p53 amyloid formation contributes to tumorigenesis and can be a potential target for therapeutic intervention. This article has an associated First Person interview with the first author of the paper.

COVID-19: Loss of bridging between innate and adaptive immunity?

COVID-19 has spread to most countries in the world. However, there are some striking differences in how COVID-19 is behaving in different age groups. While data on COVID-19 is limited, children appear to be less susceptible to severe disease. These unique characteristics may be considered as a potential link to understanding the immune system and response in COVID-19 and lead to an effective cure to the disease. We suggest a possible role of loss of bridging between innate and adaptive immunity in COVID-19 and a potential treatment modality also discussed.

Mesenchymal stem cells-bridge catalyst between innate and adaptive immunity in COVID 19.

Majority of patients infected with the COVID 19 virus display a mild to moderate course of disease and spontaneously recover at 14-20 days. However, about 15% of patients progress to severe stages and 2.5% of these patients succumb to this illness. Most patients with severe disease belong to the elderly age group (<65 years of age) and have multiple associated co-morbidities. The immune responses induced by the COVID 19 virus, during the incubation and non-severe stages, requires the early initiation of a specific adaptive immune response to eliminate the virus and prevent the progress to severe stages. In patients with a dysfunctional bridge adaptive immunity, the innate immune response becomes exaggerated due to the lack of feedback from the adaptive immune cells. The resultant cytokine storm is responsible for the severe lung injury leading to acute respiratory distress syndrome seen in COVID 19 patients. Mesenchymal stem cells are known to suppress overactive immune responses as well as bring about tissue regeneration and repair. This immuno-modulatory effect of MSCs could hold potential to manage a patient with severe symptoms of COVID 19 infection due to a dysfunctional adaptive immune system.

A kit based methodology for convenient formulation of 166Ho-Chitosan complex for treatment of liver cancer.

The effectiveness of 166Ho-chitosan complex as a radiopharmaceutical for trans-arterial radiation therapy of liver cancer has been established in clinical trials. We have developed a simple kit-bade strategy for convenient formulation of therapeutically relevant doses of 166Ho-chitosan complex in a hospital radiopharmacy in order to facilitate its widespread utilization. Quality control studies established the suitability of the radiopharmaceutical formulated using the developed strategy for in vivo administration. Biodistribution studies in normal Wistar rats showed excellent retention of the radiopharmaceutical in the liver, thus, paving the way towards utility of this approach in clinical context.

Tinospora cordifolia protects against inflammation associated anemia by modulating inflammatory cytokines and hepcidin expression in male Wistar rats.

Systemic iron homeostasis dysregulation is primarily associated with inflammation- associated anemia (AI) due to hepcidin up-regulation. Tinospora cordifolia (TC) has shown remarkable anti-inflammatory properties and has been found useful in the treatment of inflammatory disorders. However, the effects and mechanisms of TC on AI have not been studied yet. We conducted in vivo and in vitro studies to evaluate the effect of TC on AI. HPLC studies were also carried out to find out active constituents in TC extract. Model system exhibiting AI was developed by repeated injections of HKBA in Wistar rats. TC treated groups showed significantly higher levels of Hb and RBC count compared to the inflammatory control group. TC treatment showed reduction in the expression of the HAMP (hepcidin) gene in the rat liver. TC extract also inhibited gene expression of inflammatory cytokines (TNF-α, IL-1ß) and decreased NO production in RAW 264.7 cells. The HPLC analysis revealed the presence of tinosporaside, which could have synergistically contributed to the above findings. Overall results indicate that TC therapy was able to maintain circulating iron through reduction of inflammatory cytokines and expression of hepcidin in rats.

Carbon nanospheres mediated nuclear delivery of SMAR1 protein (DNA binding domain) controls breast tumor in mice model.

AIM: To investigate anticancer activity of the DNA binding domain of SMAR1 (His 5) in vitro and in vivo. MATERIALS & METHODS: His 5 was conjugated to hydrothermally synthesized carbon nanospheres (CNs). Anticancer activity of CNs-His 5 was evaluated in vitro and in vivo. RESULTS: CNs- His 5 significantly reduced cyclin D1 levels in MDA-MB-231 cells. Tumor bearing Balb/c mice injected with CNs-His 5 showed approximately 62% tumor regression and significantly reduced 18FDG uptake. Caspases assay and IHC staining confirmed tumor growth inhibition, which could be attributed to apoptotic, antiproliferative and antiangiogenic activities of His 5. CONCLUSION: DNA binding domain of the SMAR1 protein (His 5) has potent anticancer activity and its CNs mediated delivery could control breast tumor in mice model.

The application of mesenchymal stem cells to treat thermal and radiation burns.

Mesenchymal stem cells (MSCs) have been developed for a number of indications due to their regenerative and anti-inflammatory phenotypes and their utility is enhanced by the fact that allogeneic transplant is feasible with this cell type. Animal studies and early human cases indicate that this has the potential to be an exciting new therapy for treating chronic non-healing wounds such as diabetic ulcers, burns and cutaneous radiation burns. This review will focus on the use of MSCs to treat thermal and radiation burns. Large, severe burns are difficult to treat and pose a major public health burden worldwide. They are characterized by an extensive loss of the outer protective barrier, delayed wound healing, increased oxidative stress and a heightened inflammatory state. The breakdown of the protective barrier results in increased susceptibility to fluid loss and bacterial sepsis. In the case of radiation burns, chronic inflammation can result in subsequent waves of tissue injury leading to skin breakdown and necrosis. The aim of this review is to summarize the current knowledge on MSCs in treating thermal and radiation burns along with the specific scope of characterizing the biologic function of MSCs that help enhance wound healing in these chronic injuries.

In vitro and in vivo studies of a novel bacterial cellulose-based acellular bilayer nanocomposite scaffold for the repair of osteochondral defects.

Bacterial cellulose (BC) is a naturally occurring nanofibrous biomaterial which exhibits unique physical properties and is amenable to chemical modifications. To explore whether this versatile material can be used in the treatment of osteochondral defects (OCD), we developed and characterized novel BC-based nanocomposite scaffolds, for example, BC-hydroxyapatite (BC-HA) and BC-glycosaminoglycans (BC-GAG) that mimic bone and cartilage, respectively. In vitro biocompatibility of BC-HA and BC-GAG scaffolds was established using osteosarcoma cells, human articular chondrocytes, and human adipose-derived mesenchymal stem cells. On subcutaneous implantation, the scaffolds allowed tissue ingrowth and induced no adverse immunological reactions suggesting excellent in vivo biocompatibility. Implantation of acellular bilayered scaffolds in OCD created in rat knees induced progressive regeneration of cartilage tissue, deposition of extracellular matrix, and regeneration of subchondral bone by the host cells. The results of micro-CT revealed that bone mineral density and ratio of bone volume to tissue volume were significantly higher in animals receiving bilayered scaffold as compared to the control animals. To the best of our knowledge, this study proves for the first time, the functional performance of acellular BC-based bilayered scaffolds. Thus, this strategy has great potential for clinical translation and can be used in repair of OCD.

Therapeutic efficacy of multipotent adult progenitor cells versus mesenchymal stem cells in experimental autoimmune encephalomyelitis.

AIM: In this study, we have evaluated the therapeutic efficacy of mouse multipotent adult progenitor cells (mMAPCs) in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, and compared it with mouse mesenchymal stem cells (mMSCs). MATERIALS & METHODS: We administered PKH26-labeled mMAPC and mMSC into EAE mice and evaluated their therapeutic efficacy. RESULTS: The mMAPC-treated mice in comparison with the mMSC group exhibited a higher suppression of EAE (p < 0.05), and a higher fold expression of neuronal genes GAP43, NG2, PDGFR, Nestin, SMI 32, BDNF and NT 3 in spinal cord (p < 0.05), suggesting a better neuroprotective and regenerative potential of mMAPC than mMSC. CONCLUSION: MAPC may be a potential cell type, which is superior to mesenchymal stem cell for the treatment of EAE/multiple sclerosis.

Arsenic and fluoride contaminated groundwaters: A review of current technologies for contaminants removal.

Chronic contamination of groundwaters by both arsenic (As) and fluoride (F) is frequently observed around the world, which has severely affected millions of people. Fluoride and As are introduced into groundwaters by several sources such as water-rock interactions, anthropogenic activities, and groundwater recharge. Coexistence of these pollutants can have adverse effects due to synergistic and/or antagonistic mechanisms leading to uncertain and complicated health effects, including cancer. Many developing countries are beset with the problem of F and As laden waters, with no affordable technologies to provide clean water supply. The technologies available for the simultaneous removal are akin to chemical treatment, adsorption and membrane processes. However, the presence of competing ions such as phosphate, silicate, nitrate, chloride, carbonate, and sulfate affect the removal efficiency. Highly efficient, low-cost and sustainable technology which could be used by rural populations is of utmost importance for simultaneous removal of both pollutants. This can be realized by using readily available low cost materials coupled with proper disposal units. Synthesis of inexpensive and highly selective nanoadsorbents or nanofunctionalized membranes is required along with encapsulation units to isolate the toxicant loaded materials to avoid their re-entry in aquifers. A vast number of reviews have been published periodically on removal of As or F alone. However, there is a dearth of literature on the simultaneous removal of both. This review critically analyzes this important issue and considers strategies for their removal and safe disposal.

Fetal Kidney Cells Can Ameliorate Ischemic Acute Renal Failure in Rats through Their Anti-Inflammatory, Anti-Apoptotic and Anti-Oxidative Effects.

Fetal kidney cells may contain multiple populations of kidney stem cells and thus appear to be a suitable cellular therapy for the treatment of acute renal failure (ARF) but their biological characteristics and therapeutic potential have not been adequately explored. We have culture expanded fetal kidney cells derived from rat fetal kidneys, characterized them and evaluated their therapeutic effect in an ischemia reperfusion (IR) induced rat model of ARF. The fetal kidney cells grew in culture as adherent spindle shaped/polygonal cells and expressed CD29, CD44, CD73, CD90, CD105, CD24 and CD133 markers. Administration of PKH26 labeled fetal kidney cells in ARF rats resulted in a significant decrease in the levels of blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decreased tubular necrosis in the kidney tissues (p<0.05 for all). The injected fetal kidney cells were observed to engraft around injured tubular cells, and there was increased proliferation and decreased apoptosis of tubular cells in the kidneys (p<0.05 for both). In addition, the kidney tissues of ARF rats treated with fetal kidney cells had a higher gene expression of renotropic growth factors (VEGF-A, IGF-1, BMP-7 and bFGF) and anti-inflammatory cytokine (IL10); up regulation of anti-oxidative markers (HO-1 and NQO-1); and a lower Bax/Bcl2 ratio as compared to saline treated rats (p<0.05 for all). Our data shows that culture expanded fetal kidney cells express mesenchymal and renal progenitor markers, and ameliorate ischemic ARF predominantly by their anti-apoptotic, anti-inflammatory and anti-oxidative effects.