Journal of Stem Cells & Regenerative Medicine最新文献

{"title":"The Role of microRNAs in Embryonic and Induced Pluripotency.","authors":"Abbas Beh-Pajooh,&nbsp;Tobias Cantz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Research on stem cells is one of the fastest growing areas of regenerative medicine that paves the way for a comprehensive solution to cell therapy. Today, stem cells are precious assets for generating different types of cells derived from either natural embryonic stem (ES) cells or induced pluripotent stem (iPS) cells. The iPS technology can revolutionize the future of clinics by offering personalized medicine, which will provide the future treatment for curing untreatable diseases. Although iPS cell therapy is now at its infancy, promising research has motivated scientists to pursue this therapeutic approach. In this article, we provide information regarding similarities and differences between ES and iPS cells, and focus on the non-integrating methods of iPS generation via RNA molecules, especially microRNAs with an emphasis on the elucidation of their role and importance in pluripotency.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"14 1","pages":"3-9"},"PeriodicalIF":2.7,"publicationDate":"2018-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36322503","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":"Re-Defining Stem Cell-Cardiomyocyte Interactions: Focusing on the Paracrine Effector Approach.","authors":"Samiksha Mahapatra,&nbsp;Dianna Martin,&nbsp;G Ian Gallicano","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Stem cell research for treating or curing ischemic heart disease has, till date, culminated in three basic approaches: the use of induced pluripotent stem cell (iPSC) technology; reprogramming cardiac fibroblasts; and cardiovascular progenitor cell regeneration. As each approach has been shown to have its advantages and disadvantages, exploiting the advantages while minimizing the disadvantages has been a challenge. Using human germline pluripotent stem cells (hgPSCs) along with a modified version of a relatively novel cell-expansion culture methodology to induce quick, indefinite expansion of normally slow growing hgPSCs, it was possible to emphasize the advantages of all three approaches. We consistently found that unipotent germline stem cells, when removed from their niche and cultured in the correct medium, expressed endogenously, pluripotency genes, which induced them to become hgPSCs. These cells are then capable of producing cell types from all three germ layers. Upon differentiation into cardiac lineages, our data consistently showed that they not only expressed cardiac genes, but also expressed cardiac-promoting paracrine factors. Taking these data a step further, we found that hgPSC-derived cardiac cells could integrate into cardiac tissue <i>in vivo</i>. Note, while the work presented here was based on testes-derived hgPSCs, data from other laboratories have shown that ovaries contain very similar types of stem cells that can give rise to hgPSCs. As a result, hgPSCs should be considered a viable option for eventual use in patients, male or female, with ischemic heart disease.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"14 1","pages":"10-26"},"PeriodicalIF":2.7,"publicationDate":"2018-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36322505","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":"Generation of dopamine neuronal-like cells from induced neural precursors derived from adult human cells by non-viral expression of lineage factors.","authors":"Rebecca Playne,&nbsp;Kathryn Jones,&nbsp;Bronwen Connor","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Reprogramming technology holds great promise for the study and treatment of Parkinson's disease (PD) as patient-specific ventral midbrain dopamine (vmDA) neurons can be generated. This should facilitate the investigation of early changes occurring during PD pathogenesis, permitting the identification of new drug targets and providing a platform for drug screening. To date, most studies using reprogramming technology to study PD have employed induced pluripotent stem cells. Research into PD using direct reprogramming has been limited due to an inability to generate high yields of authentic human vmDA neurons. Nevertheless, direct reprogramming offers a number of advantages, and development of this technology is warranted. Previous reports have indicated that induced neural precursors (iNPs) derived from adult human fibroblasts by lineage factor-mediated direct reprogramming can give rise to dopamine neurons expressing tyrosine hydroxylase (TH+). Using normal adult human fibroblasts, the present study aimed to extend these findings and determine the capacity of iNPs for generating vmDA neurons, with the aim of utilising this technology for the future study of PD. While iNPs expressed late vmDA fate markers such as NURR1 and PITX3, critical early regional markers LMX1A, FOXA2 and EN1 were not expressed. Upon differentiation, iNPs gave rise to dopamine neuronal-like cells expressing TUJ1, TH, AADC, DAT, VMAT2 and GIRK2. To induce an authentic A9 phenotype, a series of experiments investigated temporal exposure to patterning factors. Exposure to SHH-C24II, purmorphamine, CHIR99021 and/or FGF8b during or after reprogramming was insufficient to induce expression of early vmDA regional markers. Addition of LMX1A/FOXA2 to the transfection cocktail did not induce a sustained vmDA iNP phenotype. This study reports for the first time that iNPs derived from healthy adult human cells by non-viral expression of lineage factors can give rise to dopamine neuronal-like cells. Direct-to-iNP reprogramming could be a suitable strategy for modelling PD in vitro using aged donor-derived cells.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"14 1","pages":"34-44"},"PeriodicalIF":2.7,"publicationDate":"2018-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36322506","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":"Proliferation, migration and differentiation potential of human mesenchymal progenitor cells derived from osteoarthritic subchondral cancellous bone.","authors":"Jan Philipp Krüger,&nbsp;Andreas Enz,&nbsp;Sylvia Hondke,&nbsp;Alice Wichelhaus,&nbsp;Michaela Endres,&nbsp;Thomas Mittlmeier","doi":"","DOIUrl":"","url":null,"abstract":"<p><p><b>Background:</b> For regenerative therapies in the orthopedic field, one prerequisite for therapeutic success in the treatment of cartilage defects is the potential of body's own cells to migrate, proliferate and differentiate into functional cells. While this has been demonstrated for mesenchymal stem and progenitor cells (MPC) from healthy tissue sources, the potential of cells from degenerative conditions is unclear. In this study the regenerative potential of MPC derived from subchondral cancellous bone with diagnosed osteoarthritis is evaluated <i>in vitro</i>. <b>Methods:</b> OaMPC isolated from bone chips of three individual patients with Kellgren grade 3 osteoarthritis were characterized by analysis of cell surface antigen pattern. Cell proliferation was evaluated by doubling time and population doubling rate. Cell migration was assessed using a multi-well migration assay. Multi-lineage potential was evaluated by histological staining of adipogenic, osteogenic and chondrogenic markers. In addition, chondrogenic differentiation was verified by qPCR. <b>Results:</b> OaMPC showed a stable proliferation and a typical surface antigen pattern known from mesenchymal stem cells. Cell migration of oaMPC can be induced by human blood serum. OaMPC were capable of adipogenic, osteogenic and chondrogenic differentiation comparable to MPC derived from healthy conditions. <b>Conclusion:</b> OaMPC derived from knee joints affected by osteoarthritic conditions showed regeneration potential regarding migration, proliferation and chondrogenic differentiation. This suggests that oaMPC are able to contribute to cartilage repair tissue formation.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"14 1","pages":"45-52"},"PeriodicalIF":2.7,"publicationDate":"2018-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36322507","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":"Granulation tissue-derived mesenchymal stromal cells: a potential application for burn wound healing in pediatric patients.","authors":"Gloria Pelizzo,&nbsp;Maria Antonietta Avanzini,&nbsp;Melissa Mantelli,&nbsp;Stefania Croce,&nbsp;Alice Maltese,&nbsp;Elettra Vestri,&nbsp;Annalisa De Silvestri,&nbsp;Elena Percivalle,&nbsp;Valeria Calcaterra","doi":"","DOIUrl":"","url":null,"abstract":"<p><p><b>Objective:</b> Multipotential cells are mobilized into peripheral blood in response to trauma, in particular in severe burns. These cells migrate to the site of injury in response to chemotactic signals to modulate inflammation, repair damaged tissue and facilitate tissue regeneration. We evaluated the possibility of isolating and <i>in vitro</i> expand mesenchymal stromal cells (MSCs) from granulation tissue (GT) during debridement of a burn wound, as a persective strategy to improve skin regeneration. <b>Methods:</b> GT obtained from a 12-month-old burn patient was <i>in vitro</i> cultured. Expanded MCSs were characterized for morphology, immunophenotype, differentiation capacity and proliferative growth. Antifibrotic features were also evaluated. <b>Results:</b> It was possible to isolate and <i>in vitro</i> expand cells from GT with the morphology, phenotype, proliferative and differentiation capacity typical of MSC, these cells were defined as GT-MSC. GT-MSCs exhibited antifibrotic features by releasing soluble factors, this activity was superior to that observed in BM-MSC. <b>Conclusions:</b> Successful isolation and expansion of MSCs from GT is reported. Considering their functional characteristics, GT-MSCs could be considered a good candidate adjuvant therapy to improve burn wound healing, particularly in pediatrics.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"14 1","pages":"53-58"},"PeriodicalIF":2.7,"publicationDate":"2018-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36322508","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":"Germline Stem Cells in Myocardial Regeneration - A new hope worth a delve.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"14 1","pages":"1-2"},"PeriodicalIF":2.7,"publicationDate":"2018-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41134105","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":"Biomimicry in mending the broken heart; Will hypoxia and pulsatile flow play Cupids?","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"13 2","pages":"33-34"},"PeriodicalIF":2.7,"publicationDate":"2017-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35786122","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 motility of mesenchymal stem cells is correlated with inhibition of stimulated peripheral blood mononuclear cells <i>in vitro</i>.","authors":"Alessandro Bertolo,&nbsp;David Pavlicek,&nbsp;Armin Gemperli,&nbsp;Martin Baur,&nbsp;Tobias Pötzel,&nbsp;Jivko Stoyanov","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Immunomodulatory properties of mesenchymal stem cells (MSC) are key components of their successful applications in clinical setting. However, treatments based on MSC immunomodulation need understanding of cell characteristics before cell transplantation. We used live-imaging to test the suitability of the MSC motility as a parameter for quick prediction of the immunomodulatory potential of human MSC in regulating the activity of stimulated peripheral blood mononuclear cells (PBMC) <i>in vitro</i>. Bone marrow MSC, from various donors and <i>in vitro</i> passages, were cultured with or without stimulated PBMC. After seven days, immunomodulation was assessed by measuring PBMC proliferation, IgG production and cytokine secretion in MSC and PBMC monocultures and co-cultures, and results were correlated to MSC motility. In co-culture, we observed that MSC successfully inhibited PBMC activity, reducing PBMC proliferation and IgG production compared to PBMC monoculture. MSC modulated PBMC to reduce the secretion of TNFα and IL-10, increase IL-6, G-CSF and MCP-1, while GM-CSF was not affected. By live-imaging tracking of cell trajectories, we observed that fast moving MSC were inhibiting more efficiently stimulated PBMC compared to slow ones. In co-culture, fast MSC were more effective in inhibiting IgG production (˜30% less IgG), and secreted higher levels of IL-10 (˜10% increase) and GM-CSF (˜20% increase) compared to slower cells. Furthermore, fast MSC in monocultures produced 2.3-fold more IL-6, 1.5-fold MCP-1 and 1.2-fold G-CSF in comparison to slower cells. In conclusion, live-imaging cell tracking allowed us to develop an indicative assay of the immune-regulatory potential of MSC prior to <i>in vivo</i> administration. Key Words: Human mesenchymal stem cells, Immunomodulatory potential, In vitro cell motility, Stem cell transplantation.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"13 2","pages":"62-74"},"PeriodicalIF":2.7,"publicationDate":"2017-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35786129","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":"Cathepsin K Localizes to Equine Bone <i>In Vivo</i> and Inhibits Bone Marrow Stem and Progenitor Cells Differentiation <i>In Vitro</i>.","authors":"Hayam Hussein, Prosper Boyaka, Jennifer Dulin, Duncan Russell, Lauren Smanik, Mohamed Azab, Alicia L Bertone","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Selective inhibition of Cathepsin K (CatK) has a promising therapeutic potential for diseases associated with bone loss and osseous inflammation, such as osteoarthritis, periodontitis, and osteoporosis. In horses, stress-related bone injuries are common and accompanied by bone pain and inflammation resulting in excessive bone resorption and periostitis. VEL-0230 is a highly selective inhibitor of CatK that significantly decreased bone resorption and increased bone formation biomarkers. The goal of this study was to demonstrate the presence of CatK in equine bone and a simultaneous influence on the bone marrow cellular components including function and differentiation. Our objectives were: 1) to investigate the tissue localization of CatK protein in equine bone using immunohistochemistry, and 2) to determine the effect of CatK inhibition on osteoclastogenic, chondrogenic and osteogenic differentiation potential of equine stem and progenitor cells <i>in vitro</i> using histochemical staining and differentiation-related gene expression analyses. Bone biopsies, harvested from the tuber coxae and proximal phalanx of six healthy horses, were processed for immunostaining against CatK. Sternal bone marrow aspirates were cultured in 0, 1, 10, or 100 μM of VEL-0230 and subsequent staining scoring and gene expression analyses performed. All cells morphologically characterized as osteoclasts and moderate number of active bone lining osteoblasts stained positive for CatK. Histochemical staining and gene expression analyses revealed a significant increase in the osteoclastogenic, chondrogenic and osteogenic differentiation potential of equine bone marrow cells, which was VEL-0230-concentration dependent for the latter two. These results suggested that CatK inhibition may have anabolic effects on bone and cartilage regeneration that may be explained as a feedback response to CatK depletion. In conclusion, the use of CatK inhibition to reduce inflammation and associated bone resorption in equine osseous disorders may offer advantages to other therapeutics that would require further study.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"13 2","pages":"45-53"},"PeriodicalIF":2.7,"publicationDate":"2017-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35786125","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":"Neural stem/progenitor cells maintained <i>in vitro</i> under different culture conditions alter differentiation capacity of monocytes to generate dendritic cells.","authors":"Alexey Yu Lupatov,&nbsp;Rimma A Poltavtseva,&nbsp;Oxana A Bystrykh,&nbsp;Konstantin N Yarygin,&nbsp;Gennady T Sukhikh","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cell therapy of the nervous system disorders using neural stem/progenitor cells (NSPCs) proved its efficacy in preclinical and pilot clinical studies. The mechanisms of the beneficial effects of NSPCs transplantation include replacement of damaged cells, paracrine activation of the regeneration, and immunomodulation. Detailed assessment of NSPCs-induced immunomodulation can contribute to better control of autoimmune reactions and inflammation in patients with neurodegenerative diseases. Interactions of NSPCs with dendritic cells (DCs), the key players in the induction of the immune system response to antigens are of particular interest. Here, we demonstrate that co-culturing of monocytes with NSPCs obtained and grown utilizing serum-containing medium instead of growth factor-containing serum-free medium, results in total suppression of monocyte differentiation into DCs. The effect is similar to the action of mesenchymal stem cells (MSCs). No significant effect on DCs maturation was observed. Cultures of NSPCs set up and maintained in serum-free medium have no influence on monocyte differentiation and DCs maturation. Therefore, the effects of NSPCs upon DC differentiation from monocytes strongly depend on culture conditions, whereas the molecular marker expression patterns are similar in both types of NSPCs cultures. In broader prospective, it means that cells with almost identical phenotypes can display opposite immunological properties depending upon culture conditions. It should be taken into account when developing NSPCs-based cell products for regenerative medicine.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"13 2","pages":"54-61"},"PeriodicalIF":2.7,"publicationDate":"2017-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35786126","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}