{"title":"Reciprocal signals between nerve and epithelium: how do neurons talk with epithelial cells?","authors":"Sadaruddin Chachar, Jing Chen, Yumei Qin, Xia Wu, Haiyan Yu, Qiang Zhou, Xiaojiao Fan, Chaochen Wang, Isaac Brownell, Ying Xiao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Most epithelium tissues continuously undergo self-renewal through proliferation and differentiation of epithelial stem cells (known as homeostasis), within a specialized stem cell niche. In highly innervated epithelium, peripheral nerves compose perineural niche and support stem cell homeostasis by releasing a variety of neurotransmitters, hormones, and growth factors and supplying trophic factors to the stem cells. Emerging evidence has shown that both sensory and motor nerves can regulate the fate of epithelial stem cells, thus influencing epithelium homeostasis. Understanding the mechanism of crosstalk between epithelial stem cells and neurons will reveal the important role of the perineural niche in physiological and pathological conditions. Herein, we review recent discoveries of the perineural niche in epithelium mainly in tissue homeostasis, with a limited touch in wound repair and pathogenesis.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"10 4","pages":"56-67"},"PeriodicalIF":1.8,"publicationDate":"2021-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610808/pdf/ajsc0010-0056.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39679896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of mesenchymal stem cells in the healing of anastomosed carotid arteries.","authors":"Mohamed Sa Mohamed","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cell therapies could be the future of medicine. Many centers worldwide consider the use of stem cells to treat certain conditions. Well, proper homing remains the challenge, which means the ability to target the cells to the targeted site. Intraoperative transplantation of stem cells can overcome the homing challenge. However, it could be a double-edged sword, if a proper technique was not conducted. In this comment, a practical example of that is presented, where the use of stem cells in the vascular and neurovascular surgeries shows a promising potential, but the way in which the cells are processed and introduced is a critical step that should be given a lot of attention.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"10 3","pages":"53-55"},"PeriodicalIF":1.8,"publicationDate":"2021-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449140/pdf/ajsc0010-0053.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39440638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pia Montanucci, Teresa Pescara, Alessia Greco, Daniela Francisci, Giuseppe Basta, Riccardo Calafiore
{"title":"Microencapsulated Wharton Jelly-derived adult mesenchymal stem cells as a potential new therapeutic tool for patients with COVID-19 disease: an in vitro study.","authors":"Pia Montanucci, Teresa Pescara, Alessia Greco, Daniela Francisci, Giuseppe Basta, Riccardo Calafiore","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>The recent newly appeared Coronavirus disease (COVID-19), caused by an enveloped RNA virus named \"severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)\", is associated with severe respiratory morbidity and mortality. Recent studies have shown that lymphopenia and a cytokine mass release represent important pathogenic features, with clinical evidence of dyspnea and hypoxemia, often leading to acute respiratory distress syndrome (ARDS), in severely ill patients, with a high death toll. Currently, stem cells are actively being investigated for their potential use in many \"untreatable\" diseases. In this regard and in particular, Mesenchymal Stem Cells (MSC), due to their intrinsic features, including either ability to impact on regulation of the immune system, or association with both anti-viral and anti-inflammatory properties, or potential for differentiation into several cell lineages, have become a promising tool for cell and molecular-based therapies. On this background, we wished to explore whether human umbilical cord-derived mesenchymal stem cells (hUCMS) would represent a potential viable therapeutic approach for the management of critically ill COVID19 patients.</p><p><strong>Methods: </strong>We tested the hUCMS effects on peripheral blood mononuclear cell (PBMCs) retrieved from patients with COVID19 (Ethical Committee CEAS Umbria, Italy CER N°3658/20 7, May, 2020), both as free cell monolayers and after envelopment in sodium alginate microcapsules. Both cell systems, after priming with IFN-γ, proved able to produce several immunomodulatory molecules such as IDO1 and HLAG5, although only the microencapsulated hUCMS were associated with massive and dose-dependent production of these factors.</p><p><strong>Results: </strong>The microencapsulated hUCMS improved allo-suppression in mixed lymphocytes reactions (MLRs), while also blunting T helper 1 and T helper 17 responses, that are involved with the cytokine storm and greatly contribute to the patient death. Moreover, we observed that both free and microencapsulated hUCMS permitted 5 days survival of in vitro culture maintained PBMCs extracted from very ill patients.</p><p><strong>Conclusion: </strong>We have provided evidence that microencapsulated hUCMS in vitro, seem to represent a powerful tool to impact on several immune pathways, clearly deranged in COVID19 patients. Further study is necessary to begin in vivo assessment of this experimental system, upon determining both, the most appropriate time of the disease onset for intervention, and cell dosage/patient of our experimental product.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"10 3","pages":"36-52"},"PeriodicalIF":1.8,"publicationDate":"2021-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449139/pdf/ajsc0010-0036.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39440637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cancer stem cells in head and neck cancer.","authors":"Hector Picon, Achuta Kumar Guddati","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) are a unique population of cells found within tumors that are able to self-renew, restore the original heterogeneity of a tumor following treatment, and show increased tumorigenic potential when compared to other cancer cells. It is thought that they are responsible for the recurrence of tumors as well as the resistance to treatment that is seen clinically. CSCs are known to be involved in head and neck cancer (HNCs) specifically, as evidence for their existence can be found in head and neck squamous cell carcinoma (HNSCC), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC), among others. Here, findings from various approaches to identifying and targeting CSCs and their downstream effectors in HNC are summarized, with an emphasis on recent advancements. Prognostic and therapeutic markers are discussed for each specific type of HNC, and novel treatment strategies and current clinical trials involving CSCs are detailed as well. The information provided here is intended to further the research on this important topic and lead to clinical impact in the battle against HNC.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"10 3","pages":"28-35"},"PeriodicalIF":1.8,"publicationDate":"2021-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449141/pdf/ajsc0010-0028.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39440187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Olusola Jumoke Daramola, Stephen Osasan, Hebah Ali, Perpetua Emeagi
{"title":"Hematopoietic stem and progenitor cells directly participate in host immune response.","authors":"Olusola Jumoke Daramola, Stephen Osasan, Hebah Ali, Perpetua Emeagi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The properties of hematopoietic stem and progenitor cells (HSPCs), including self-renewal and pluripotency, have been extensively studied. These features have been explored in the management of several haematological disorders and malignancies. Although their role as precursors of innate immune cells is well understood, little is known about their direct participation in host immune response. In this review, we explicate the direct role of HSPCs in the host immune response and highlight therapeutic options for the infectious disease burden that is currently ravaging the world, including COVID-19.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"10 2","pages":"18-27"},"PeriodicalIF":1.8,"publicationDate":"2021-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310832/pdf/ajsc0010-0018.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39258402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adrian Moratilla, Diego Sainz de la Maza, Marta Cadenas Martin, Pilar López-Iglesias, Pilar González-Peramato, Maria P De Miguel
{"title":"Inhibition of PKCε induces primordial germ cell reprogramming into pluripotency by HIF1&2 upregulation and histone acetylation.","authors":"Adrian Moratilla, Diego Sainz de la Maza, Marta Cadenas Martin, Pilar López-Iglesias, Pilar González-Peramato, Maria P De Miguel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Historically, primordial germ cells (PGCs) have been a good model to study pluripotency. Despite their low numbers and limited accessibility in the mouse embryo, they can be easily and rapidly reprogrammed at high efficiency with external physicochemical factors and do not require transcription factor transfection. Employing this model to deepen our understanding of cell reprogramming, we specifically aimed to determine the relevance of Ca<sup>2+</sup> signal transduction pathway components in the reprogramming process. Our results showed that PGC reprogramming requires a normal extracellular [Ca<sup>2+</sup>] range, in contrast to neoplastic or transformed cells, which can continue to proliferate in Ca<sup>2+</sup>-deficient media, differentiating normal reprogramming from neoplastic transformation. Our results also showed that a spike in extracellular [Ca<sup>2+</sup>] of 1-3 mM can directly reprogram PGC. Intracellular manipulation of Ca<sup>2+</sup> signal transduction pathway components revealed that inhibition of classical Ca<sup>2+</sup> and diacylglycerol (DAG)-dependent PKCs, or intriguingly, of only the novel DAG-dependent PKC, PKCε, were able to induce reprogramming. PKCε inhibition changed the metabolism of PGCs toward glycolysis, increasing the proportion of inactive mitochondria. This metabolic switch from oxidative phosphorylation to glycolysis is mediated by hypoxia-inducible factors (HIFs), given we found upregulation of both HIF1α and HIF2α in the first 48 hours of culturing. PKCε inhibition did not change the classical pluripotency gene expression of PGCs, Oct4, or Nanog. PKCε inhibition changed the histone acetylation of PGCs, with histones H2B, H3, and H4 becoming acetylated in PKCε-inhibited cultures (markers were H2BacK20, H3acK9, and H4acK5K8, K12, K16), suggesting that reprogramming by PKCε inhibition is mediated by histone acetylation.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"10 1","pages":"1-17"},"PeriodicalIF":1.8,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012778/pdf/ajsc0010-0001.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25558623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"HspB5 protects mouse neural stem/progenitor cells from paraquat toxicity.","authors":"Naveen Kumar Mekala, Shyama Sasikumar, Kranthi Kiran Akula, Yash Parekh, Ch Mohan Rao, Kiran Kumar Bokara","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>HspB5 (αB-crystallin) is known to be involved in a variety of cellular functions, including, protection of cells from oxidative damage and inhibiting apoptosis. Neural stem/progenitor cells (NSPCs) have significant therapeutic value, especially in the NSC/NPC transplantation therapy. However, the viability of the transplanted NSPCs remains low because of various factors, including oxidative stress.</p><p><strong>Objective: </strong>The current investigation explored the possible role of HspB5 in the protection of mouse NSPCs (<i>m</i>NSPCs) against paraquat-induced toxicity.</p><p><strong>Methods: </strong>The recombinant human HspB5 was expressed in <i>E.coli</i> and was purified using gel filtration and Ion-exchange chromatography. The biophysical characterization of HspB5 was carried out using DLS, CD, and Analytical Ultracentrifugation (SV); the chaperone activity of HspB5 was determined by alcohol dehydrogenase aggregation assay. We have subjected the mNSPCs to paraquat-induced oxidative stress and monitored the protective ability of HspB5 by MTT assay and Hoechst-PI staining. Furthermore, increase in the expression of the anti-apoptotic protein, procaspase-3 was monitored using western blotting.</p><p><strong>Results: </strong>The recombinant HspB5 was purified to its homogeneity and was characterized using various biophysical techniques. The externally added FITC-labeled HspB5 was found to be localized within the cytoplasm of <i>m</i>NSPCs. Our Immunocytochemistry results showed that the externally added FITC-labeled HspB5 not only entered the cells but also conferred cytoprotection against paraquat-induced toxicity. The protective events were monitored by a decrease in the PI-positive cells and an increase in the procaspase-3 expression through Immunocytochemistry and Western blotting respectively.</p><p><strong>Conclusion: </strong>Our results clearly demonstrate that exogenously added recombinant human HspB5 enters the <i>m</i>NSPCs and confers protection against paraquat toxicity.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":" ","pages":"68-77"},"PeriodicalIF":1.8,"publicationDate":"2020-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811932/pdf/ajsc0009-0068.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38854910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alok K Sharma, Nandini Gokulchandran, Pooja P Kulkarni, Hemangi M Sane, Ridhima Sharma, Alitta Jose, Prerna B Badhe
{"title":"Cell transplantation as a novel therapeutic strategy for autism spectrum disorders: a clinical study.","authors":"Alok K Sharma, Nandini Gokulchandran, Pooja P Kulkarni, Hemangi M Sane, Ridhima Sharma, Alitta Jose, Prerna B Badhe","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorders [ASD] is a lifelong disability mainly affecting the development, communication, social interaction and behavior of an individual. Cell transplantation is emerging as a potential therapeutic strategy for ASD. Our previously published proof of concept study showed beneficial effects of cell transplantation in ASD. This study shows effect of cell transplantation in a larger sample size of ASD patients.</p><p><strong>Methods: </strong>254 patients diagnosed with ASD on DSM V criteria were enrolled in this open label non-randomized study. The intervention included intrathecal transplantation of autologous bone marrow mononuclear cells and neurorehabilitation. On mean follow up of 7.50 months, percentage analysis was performed on all symptomatic changes. Changes in outcome measures, Indian Scale for Assessment of Autism [ISAA] and Childhood Autism Rating Scale [CARS], were analyzed statistically using Wilcoxon Signed-Rank Test. Comparative analysis of Positron Emission Tomography [PET CT] scan brain, performed before and 6 months after intervention, was done in 86 patients to monitor the outcome at cellular level. Change in the standardized uptake values was statistically evaluated using T-Test [P≤0.05].</p><p><strong>Results: </strong>Improvements were observed in eye contact, attention and concentration, hyperactivity, sitting tolerance, social interaction, stereotypical behavior, aggressiveness, communication, speech, command following and self-stimulatory behavior. Statistically significant improvement was observed in scores of ISAA and CARS after intervention. A significantly better outcome of the intervention was found in patients at younger age and with shorter duration of disease [<5 years from time of diagnosis]. 86 patients who underwent a repeat PET CT scan showed improved brain metabolism after intervention in areas which correlated to the symptomatic changes. No major procedure related adverse events were recorded. However, 5 patients, with history of seizure and abnormal EEG, had an episode of seizure which was managed using medications. Outcome of intervention in these patients was not affected by seizures as improvements were observed in them.</p><p><strong>Conclusion: </strong>The results of this study indicate that autologous bone marrow mononuclear cells in combination with neurorehabilitation are a safe and effective treatment modality for ASD. It improves the quality of life of patients and helps them to integrate in mainstream lifestyle.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":" ","pages":"89-100"},"PeriodicalIF":1.8,"publicationDate":"2020-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811933/pdf/ajsc0009-0089.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38854911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Can Wharton jelly derived or adipose tissue derived mesenchymal stem cell can be a treatment option for duchenne muscular dystrophy? Answers as transcriptomic aspect.","authors":"Eda Sun, Erdal Karaoz","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>Mesenchymal stem cells (MSCs) are able to differentiate into several cell lineages including skeletal muscle. In addition to their differentiation capacities, they have the ability to transfer their content genomic information horizontally through their exosomes and fusion abilities, as we have shown in our previous clinic study on Duchenne Muscular Dystrophy (DMD) patients, dystrophin expression increased after MSC treatment. Therefore, this study aimed to compare the transcriptomic properties of Wharton's jelly derived (WJ-) MSC and Adipose tissue (AT-) derived MSC, which are the two most preferred sources in MSC treatments applied in DMD.</p><p><strong>Methods: </strong>Both MSC cell lines obtained from ATCC (PCS-500-010; PCS-500-011) were characterized by flow cytometry then WJ-MSC and AT-MSC cell lines were sequenced via RNA-SEQ. R language was used to obtain the differentially expressed genes (DEGs) and differentially expressed miRNAs, respectively. Additionally, in order to support the results of our study, a gene expression profile data set of DMD patients (GSE1004) were acquired from Gene Expression Omnibus (GEO) database.</p><p><strong>Results: </strong>Here, we demonstrated that activated WNT signaling and downregulated TGF-β pathways under the control of decreased mir-24 which are involved in myogenic differentiation are differentially expressed in WJ-MSC. We have shown that the expression of mir-199a-5p, which is known to increase in exosomes of DMD patients, is less in WJ-MSC. Additionally, we have shown activated PI3K/Akt pathway, which is controlling mitochondria transfer via Tunnelling Nanotube as a new perspective in cellular therapies in myodegenerative diseases, in WJ-MSC more than in AT-MSCs.</p><p><strong>Conclusion: </strong>Summing up, WJ-MSC, which we recommend as an appropriate source candidate due to its immune-regulation properties, stands forward as a preferable source in the cellular treatment of DMD patients due to its transcriptomic aspect.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"9 4","pages":"57-67"},"PeriodicalIF":1.8,"publicationDate":"2020-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486554/pdf/ajsc0009-0057.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38379463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Themistoklis Feretis, Charalampos Katselis, Ioannis G Papanikolaou, Konstantinos Apostolou, Spyridon Tsikalakis, Konstantinos G Toutouzas, George Theodoropoulos, Eleni Andrianna Trigka, Angelica A Saetta, Nicholas Alexakis, Manousos Konstandoulakis, Kalliopi Tsarea, Maria Karamperi, Dimitrios Kletsas, Efstratios Patsouris, Andreas Manouras, Georgios C Zografos, Apostolos Papalois
{"title":"ATSC transplantation contributes to liver regeneration following paracetamol-induced acute liver injury through differentiation into hepatic-like cells.","authors":"Themistoklis Feretis, Charalampos Katselis, Ioannis G Papanikolaou, Konstantinos Apostolou, Spyridon Tsikalakis, Konstantinos G Toutouzas, George Theodoropoulos, Eleni Andrianna Trigka, Angelica A Saetta, Nicholas Alexakis, Manousos Konstandoulakis, Kalliopi Tsarea, Maria Karamperi, Dimitrios Kletsas, Efstratios Patsouris, Andreas Manouras, Georgios C Zografos, Apostolos Papalois","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>Drug-induced liver injury (DILI) is a leading cause of acute liver injury (ALI). Acetaminophen (also termed paracetamol), can often be found in drugs that may be abused (i.e., prescription for pain relief). Animal experiments have shown that mesenchymal stem cell transplantation can ameliorate or even reverse hepatic injury.</p><p><strong>Material and methods: </strong>ALI was induced in Wistar rats using paracetamol. ATSCs were transplanted via the intravenous, portal vein, or intrahepatic route directly onto the liver parenchyma. Histological evaluation was conducted to assess drug-induced injury following transplantation. Fluorescence in situ hybridization (FISH) was used to verify the location of stem cells on the liver parenchyma. The effect of those cells on liver regeneration was tested by immunohistochemistry for hepatic growth factor (HGF). In addition, reverse transcription-quantitative PCR (qRT-PCR) was used to assess hepatic growth factor (HGF), hepatic nuclear factor 4α (HNF4α), cytochrome P450 1A2 (CYP1A2) and α-fetoprotein (AFP) mRNA expression.</p><p><strong>Results: </strong>Immunohistochemical staining for HGF was stronger in the transplanted groups than that in the control group (P<0.001). HNF4α and HGF mRNA levels were increased on day 7 following transplantation (P<0.001 and P=0.009, respectively). CYP1A2 mRNA levels were also increased (P=0.013) in the intravenous groups, while AFP levels were higher in the intrahepatic groups (P=0.006). ATSC transplantation attenuates ALI injury and promotes liver regeneration. Furthermore, expression of specific hepatic enzymes points to ATSC hepatic differentiation.</p><p><strong>Conclusion: </strong>The study showed the positive effects of transplanted adipose tissue stem cells (ATSCs) on liver regeneration (LG) through hepatotrophic factors. Furthermore, increased expression of hepatic specific proteins was recorded in ATSC transplanted groups that indicate stem cells differentiation into hepatic cells.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"9 3","pages":"36-56"},"PeriodicalIF":1.8,"publicationDate":"2020-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364386/pdf/ajsc0009-0036.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38184395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}