{"title":"Clinical trial in a dish; A rewarding step towards translation & perspectives on its limitations.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"15 2","pages":"16-17"},"PeriodicalIF":2.7,"publicationDate":"2019-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971382/pdf/jsrm_15_16.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37579830","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":"Increased mesodermal and mesendodermal populations by BMP4 treatment facilitates human iPSC line differentiation into a cardiac lineage.","authors":"Maya Kimura, Hatsue Furukawa, Masanobu Shoji, Tadahiro Shinozawa","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) have attracted attention as a novel tool for drug safety screening and several differentiation protocols of hiPSC lines into cardiomyocytes have been reported; the standardization of these protocols will expand their applications for safety assessments such as \"clinical safety trial-on-dish\". Bone morphogenetic protein 4 (BMP4) is an important factor in promoting mesoderm differentiation and BMP4 treatment has been used at the early stage of cardiac differentiation into different hiPSCs. In the present study, we evaluated the effects of BMP4 treatment at the early stage of cardiac differentiation. We performed gene expression profiling of the germ layer during mesoderm differentiation of hiPSCs derived from three different donors. The expression of <i>T</i> (a mesoderm marker) and <i>GATA6</i> (an endoderm marker) increased and that of <i>PAX6</i> (a neuroectoderm marker) decreased in pooled embryoid bodies (EBs) after BMP4 treatment. Single-cell gene expression analysis revealed that mesodermal and mesendodermal populations increased in EBs derived from 253G1. Finally, BMP4 treatment increased mesodermal and mesendodermal populations compared with that without BMP4 in two other hiPSC lines, confirming the reproducibility of multiple hiPSC lines. Thus, our results suggest that BMP4 treatment increases mesodermal and mesendodermal populations at the early stage of cardiac differentiation in different hiPSC lines.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"15 2","pages":"45-51"},"PeriodicalIF":2.7,"publicationDate":"2019-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971377/pdf/jsrm_15_45.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37581111","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":"Stem cells for regenerative medicine and anti-aging.","authors":"Jurgen Hescheler","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"15 2","pages":"53"},"PeriodicalIF":2.7,"publicationDate":"2019-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971379/pdf/jsrm_15_53.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37581112","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 chemotherapy with nanosomal paclitaxel and gene therapy expressing apoptosis-inducing proteins in the management of spontaneous canine mammary neoplasm.","authors":"Mohan Divya, Swapan Kumar Maiti, Palakkara Sangeetha, Shivaramu Shivaraju, Naveen Kumar, Ashok Kumar Tiwari, Jurgen Hescheler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mammary gland tumours are the second most common neoplasm representing about 40-50% of all neoplasm after skin tumour, but the majority of these tumours occur in intact/ non spaying female dogs. Surgical excision of the benign tumour is the standard treatment of canine mammary tumours. Chemotherapy is the choice of treatment if the tumour is malignant or shows evidence of invasion into lymph or blood vessels, however, they showed different side effects and their success rate is varied. Taxanes are now the most promising anti-cancer drugs with little side effects. Gene therapy expressing apoptosis-inducing proteins have ability to kill cancer cells while sparing normal cells. The present study was conducted for exploring the oncolytic effect of viral gene therapy expressing apoptosis-inducing proteins construct (ns1 +vp3), nanosomal paclitaxel as chemotherapeutic agent and surgical therapy in the management of spontaneous canine mammary tumours. Chemotherapy (nanosomal paclitaxel) (n=10), viral gene construct (ns1 +vp3) (n=10) and surgical therapy (n=10) were used in 30 female dogs of different breeds having different types of spontaneous mammary tumours. Chemotherapeutic drug and viral gene construct (ns1 +vp3) induced apoptosis in canine mammary neoplasms were studied using fluorescent activated cell sorting analysis. However, apoptotic percentage was significantly higher in chemotherapeutic group than viral gene construct therapy. No major side effects were observed in any groups. Matrix metalloproteinase-2 was found as an important prognostic tool in the management of canine mammary tumours. In conclusion, chemotherapy with nanosomal paclitaxel proved better than viral gene construct (ns1 +vp3) in the treatment of canine mammary neoplasm.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"15 2","pages":"24-34"},"PeriodicalIF":2.7,"publicationDate":"2019-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971383/pdf/jsrm_15_24.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37582134","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":"Heterogeneity of Cells Population and Secretome Profile of Differentiated Cells from E17 Rat Neural Progenitor Cells.","authors":"Vista Budiariati, Ratih Rinendyaputri, Ariyani Noviantari, Dwi Budiono, Mokhamad Fahrudin, Berry Juliandi, Arief Boediono","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Conditioned medium has now gained increasing interest since the development of secretome-based therapy. Various types of cells have been studied as a source of the secretome. One of them is neural progenitor cells (NPCs). These are cells that capable of differentiating into neurons as well as glial cells. Indeed, the study on NPCs has risen in the last few decades, but the study on the differentiated cells has not clearly described. The most common procedures that widely used to get the conditioned medium is starvation. However, cell starvation may cause environmental stress and become an apoptotic trigger for the cells. In this study, we analyzed the effect of starvation on differentiated cells from E17 rat neural progenitor cells (NPCs) based on cells characteristics and secretome profile. We found that starvation decreased cells viability and affected the heterogeneity of the cell population. Astrocytes survived more under nutrient deprivation conditions, and the progenitor cells showed a higher tendency to differentiate to glial cells than neurons. Duration of starvation also influenced the secretome profile, alterations found in protein types and also their function in the biological process. During 24 hours of starvation, cells secreted proteins that were used to maintain cell growth, stimulate differentiation, and produce energy, but there were also proteins that identified and involved in autophagy activation. After 48 hours of starvation, astrocytes that became the dominant cells secreted proteins that try to keep protecting the remaining neurons.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"15 2","pages":"35-44"},"PeriodicalIF":2.7,"publicationDate":"2019-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971381/pdf/jsrm_15_35.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37582137","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":"Missing <i>in vitro</i> links between the origin and <i>in vivo</i> destiny of mesenchymal stem cells.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"15 1","pages":"1-2"},"PeriodicalIF":2.7,"publicationDate":"2019-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586768/pdf/jsrm_15_1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41204010","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":"What is the Best Degree of Hyaluronic Acid Crosslinking in Increasing Growth Factors Level of Platelet-Rich Fibrin Lysate?","authors":"Nora Ariyati, Kusworini Handono, Nurdiana Nurdiana, Yohanes Widodo Wirohadidjojo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p><b>Introduction:</b> Various therapeutic materials such as hyaluronic acid (HA) and platelet-rich fibrin lysate (PRF-L) have been represented to improve chronic fibroblast ulcers and premature aging. HA crosslinking is the most popular dermal filler presently in the therapy of aging skin. With the PRF-L properties that are rich in growth factors (GF), the combination of these materials is expected to produce synergistic and potentiation effects. <b>Objective:</b> This study aimed to determine the effect of various degrees of HA crosslinking on GF levels in PRF-L. <b>Materials and Methods:</b> PRF-L was obtained from PRF of healthy adult venous blood with 72 hours of incubation. HA was taken from preparations with 3 crosslinking degrees of 3%, 4%, and 10%. Measurement of GF levels was performed using sandwich ELISA method. <b>Results:</b> The GF levels released in PRF-L increased with the addition of HA crosslinking. The lower HA crosslinking degree (3%) triggered greater release of GF by PRF-L compared to higher HA crosslinking degree (4% & 10%). <b>Conclusion:</b> Low degree HA crosslinking elevated all measured GF levels in PRF-L. The lower HA crosslinking degree provoked higher release of GF.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"15 1","pages":"3-7"},"PeriodicalIF":2.7,"publicationDate":"2019-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586767/pdf/jsrm_15_3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37365356","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":"Comparative transcriptomic analysis of human mesenchymal stem cells derived from dental pulp and adipose tissues.","authors":"Atsushi Terunuma, Keisuke Ashiba, Tsubasa Takane, Yosuke Sakaguchi, Hiroshi Terunuma","doi":"","DOIUrl":"","url":null,"abstract":"<p><p><b>Objective:</b> Mesenchymal stem cells (MSCs) have been isolated from various human tissues. Although they share cardinal stem cell features of self-renewal and multi-potency, they also seem to possess distinct characteristics depending on the tissue types they originated from. When developing stem cell-based therapies, MSCs with the most desirable characteristics should be chosen. However, our knowledge on tissue type-specific characteristics of MSCs is limited. Here, we comparatively studied the gene expression profiles of MSCs from different tissue types, and predicted target diseases suitable for each type of MSCs. <b>Methods:</b> We harvested MSCs from human dental pulp and adipose tissue specimens and subjected them to gene expression microarray analysis. Characteristic gene expression signatures of the MSCs from each tissue type were identified using gene-annotation enrichment analysis. <b>Results:</b> Dental pulp-derived MSCs exhibited gene expression signatures of neuronal growth, while adipose tissue-derived MSCs exhibited signatures of angiogenesis and hair growth. MSCs from each tissue type expressed a discrete set of genes encoding secretory peptides, which may function as paracrine factors. <b>Conclusions:</b> MSCs derived from different tissue types demonstrated distinct gene expression signatures, which are suggestive of target diseases in clinical applications of the MSCs and stem cell-conditioned media. By expanding the analysis to MSCs from a wide range of tissue types, and by employing multiple omics approaches, a catalogue of MSCs and therapeutic targets can be generated.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"15 1","pages":"8-11"},"PeriodicalIF":2.7,"publicationDate":"2019-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586766/pdf/jsrm_15_8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37365357","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":"Mitochondrial distribution violation and nuclear indentations in neurons differentiated from iPSCs of Huntington's disease patients.","authors":"Evgeny D Nekrasov, Sergey L Kiselev","doi":"","DOIUrl":"","url":null,"abstract":"<p><p><b>AIM:</b> Huntington's disease (HD) is an inherited disease caused by an expansion of cytosine-adenine-guanine (CAG) repeats in the huntingtin gene (<i>HTT</i>) that ultimately leads to neurodegeneration. To study the molecular basis of this disease, induced pluripotent stem cells (iPSCs) generated from patients' fibroblasts were used to investigate axonal mitochondrial trafficking and the nature of nuclear indentations. <b>METHODS:</b> Pathological and control iPSCs generated from patients with a low number of repeats were differentiated in striatal neurons of the brain. Mitochondrial density was measured along the axon using tubulin beta 3 co-staining in pathological and control neurons. To investigate the connection of nuclear roundness with calcium dysregulation, several calcium inhibitors were used. Proteasome system inhibition was applied to mimic premature neuronal ageing. <b>RESULTS:</b> We found that the mitochondrial density was approximately 7.6 ± 0.2 in neurites in control neurons but was only 5.3 ± 0.2 in mutant neurons with 40-44 CAG repeats (p-value <0.005). Neuronal ageing induced by proteasome inhibitor MG132 significantly decreased the mitochondrial density by 15% and 25% in control and mutant neurons to 6.5 ± 0.1 (p-value < 0.005) and 4.0 ± 0.3 (p-value < 0.005), respectively. Thus, for the first time, an impairment of mitochondrial trafficking in pathological neurons with endogenous mutant huntingtin was demonstrated. We found that inhibiting the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), the ryanodine-receptor (RyR) or the inositol 1,4,5-trisphosphate receptor (IP3R) by specific inhibitors did not specifically affect the nuclear roundness or survival of pathological neurons differentiated from patient iPSCs. Therefore, nuclear calcium homeostasis is not directly associated with HD pathology. <b>CONCLUSION:</b> Identifying HD iPSCs and differentiating from them neurons provide a unique system for modelling the disease <i>in vitro</i>. Impairments of mitochondrial trafficking and nuclear roundness manifest long before the disease onset, while premature neuronal ageing enhances differences in mitochondrial distribution.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"14 2","pages":"80-85"},"PeriodicalIF":2.7,"publicationDate":"2018-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36895528","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}